On NAAS Rating: 4.55 NAAS Rating: April, 2018 Indexed in SCOPUS th -09 th 08 ICRAFPAY 2018 ICRAFPAY International Conference International Recent Advances and Future Recent Advances Perspectives in Ayurveda and Yoga Perspectives in Ayurveda Convener Special Online Issue Dr. Dev Nath Singh Gautam Organized By Supplement 2018 11 ● Supplement Volume Banaras Hindu University Rajiv Gandhi South Campus Barkachha, Mirzapur 231001

International Journal of Green Pharmacy • Volume 11 • Supplement 2018 • Pages 1-67 Study of physiological variation in serum insulin level and blood glucose level (fasting blood sugar and post prandial blood sugar) among young healthy individuals with special reference to Deha Prakriti

Abha Singh1, Girish Singh2, N. S. Tripathi1 1Department of Kriya Sharir, Faculty of Ayurveda, Institute of Medical Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India, 2Department of Community Medicine, Division of Biostatics, Institute of Medical Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India RESEARCH ARTICLE

Abstract

Prakriti is the nature, behavior, or psychosomatic constitution of an individual. It represents the doshic state of individual. Prakriti is an important tool which can affect the line of treatment/management, prognosis, diagnosis, and occurrence of the disease. Diabetes mellitus is a non-communicable, long-term metabolic disorder. Prakriti of an individual and their health along with occurrence, treatment/management as well as prognosis of a disease has a close relationship. Keeping these facts in the mind, such study has been designed to find possible relationship between level of insulin and blood glucose level in different prakriti persons. A total of 89 volunteers were registered for the purpose of the study having age group between 18 and 30 years. Prakriti was determined by pro forma designed for the same, based on Ayurvedic classics. Their blood glucose level and serum insulin level were tested. It has been observed that level of insulin was found maximum 85.846 ± 3.68 in person having Kapha Prakriti, whereas, in Pitta Prakriti individuals, serum insulin level was found in minimum (lower) range. It was also observed that mean of fasting blood sugar level was maximum in volunteers of Kapha Prakriti. Serum insulin level was found in maximum (upper) range in Kapha Prakriti person.

Key words: Blood sugar, diabetes mellitus, insulin, Madhumeha, blood sugar, Prakriti

INTRODUCTION As per Ayurveda, Agni is responsible for the various types of chemical conversion taking place in our body.[4] ccording to the WHO, approximately Insulin also performs various functions of the Agni, as it is 150 million people are suffering from involved in various metabolic processes as well as chemical Adiabetes mellitus (DM) (Madhumeha) conversions.[5] worldwide and are supposed to get double by the year 2025. Type 2 DM (T2DM) is a metabolic disorder and mainly occurs due to impaired REVIEW OF LITERATURE function of the pancreas, especially beta cell, which secretes insulin.[1] DM is a heterogeneous Prakriti disease involving various organs of the body. It is characterized by chronic enhancement of Prakriti is also known as psychosomatic constitution of an the blood sugar level due to malfunctioning of individual. Prakriti is the sum total of physical, physiological, insulin hormone, including insulin formation, secretion, and insulin resistance.[2] Address for correspondence: Dr. N. S. Tripathi, Department of Kriya Sharir, Faculty Chronic increase in the blood sugar (glucose) of Ayurveda, Institute of Medical Science, Banaras level is a leading cause of renal failure, visual Hindu University, Varanasi, Uttar Pradesh, India. E-mail: loss, hepatic disorder as well as cardiovascular [email protected] disorder.[3]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S1 Singh, et al.: Study of physiological variation in serum insulin level and blood glucose level (fasting blood sugar and post prandial blood sugar) among young healthy individuals with special reference to Deha Prakriti and psychological qualities of an individual. Prakriti untreated is eventually fatal. Glucagon deficiency can represents the doshik state of an individual. cause hypoglycemia, and glucagon excess makes diabetes worse. Excess pancreatic production of somatostatin causes hyperglycemia and other manifestation of diabetes. Formation of Prakriti

Prakriti is formed by the Utkatata (predominance) of one, two, Effect of Insulin on Carbohydrate Metabolism or all three Doshas at the time of samyoga (union) of shukra (sperm) and shonita (ovum) in the garbhashaya (uterus).[6] Insulin promotes muscle glucose uptake and metabolism. It also helps storage of glycogen in muscle. It promotes liver uptake, storage, and use of glucose. It promotes conversion of Development of Prakriti excess glucose into fatty acids and inhibits gluconeogenesis.[2] Development in this context refers to the causation of specific features in the individual of the prakiti in such a way that two persons belonging to one “prakriti” also differ from each MATERIALS AND METHODS other.[7] In our body, doshas, dhatus, and malas maintain our internal environment (homeostasis).[8] Topic of the research was passed by ethical clearance committee of the Institute of Medical Science (BHU). Vata in its normal state is responsible for all activities of the body. Vata, in fact, constitutes the life of living beings.[9] For the purpose of the present study, a total of 89 volunteers Vitiation of Tridosha (Vata, Pitta, and Kapha) may be taking who were registered having age group between 18 and place in different seasons as for example - physiological 30 years were selected. predominance of vata dosha is seen in varsha ritu (Rainy season). Hence, the Prakriti formed in this season (due to Exclusion Criteria fertilization) may be mostly Vatika in nature.[10] 1. Subjects aged <18 years or more than 30 years were Various researches have been done, taking Prakriti into excluded. consideration. The mean of serum urea was observed 2. Only young healthy individuals were selected for the maximum (nearer to upper normal limit) in shishir ritu and study. Subjects not fulfilling the criteria of “Clinically minimum (nearer to lower normal limit in grishma ritu in all Healthy” status as per the pro forma were excluded. Prakriti group). Prakriti also affects the serum urea level in 3. The subjects, who were known to have any disease/ [11] different season. Incidence of occurrence of amavata is chronic illnesses before or during study, were excluded. found considerably high among Kapha Prakriti, whereas low in Vataja Prakriti. Pitta Prakriti cases shown a high percentage of recovery rate than kaphaj and vataj.[12] Seasons influence Assesment of Prakriti the aggravation, accumulation, and pacification of humors, which might affect the functions in various constitutions.[13] Subjects were assessed to understand their Prakriti using Prakriti assessment pro forma Vandana et al., (2009). There are many factors determines the uniqueness of Prakriti. Acharya Charka has described six Bhavas which are the Volunteers were assessed for their health by general health determinant of the development of Garbha. (Ch.Sha.3/3).[14] examination pro forma.

Vagbhata has also mentioned that Prakriti is dependent not only on Prakriti of the subjects based on most dominant Dosha was Shukra and Shonita but also on diet and behavior of the pregnant categorized into 1. Vataja Prakriti (includes Vata-Pitta and women, nature of Garbhasya and Kala (A.H.Sha.3/83).[15] Vata-Kapha), 2. Pittaja Prakriti (includes Pitta-Vata and Pitta-Kapha), and 3. Kaphaja Prakriti (includes Kapha-Vata Acharya Charaka considers that Dehagni (Jaṭharagni) is the and Kapha-Pitta) Prakriti. cause of life, complexion, strength, health, nourishment, lusture, oja, teja (energy), and prana (life energy) (Ch.Chi. 15/5).[16] Estimation of Serum Insulin Level Insulin is anabolic, increasing the storage of glucose, fatty Measurement of serum insulin level was done in the acids, and amino acids. Glucagon is catabolic, from glucose, Department of Kriya Sharir, Faculty of Ayurveda, Institute of fatty acids, and the amino acids ores into the bloodstream. Medical Science, Banaras Hindu University, Varanasi. The two hormones are thus in their overall action and are reciprocally secreted most circumstances. Insulin excess causes hypoglycemia, which leads to convulsions and coma. Collection of Venous Blood Madhumeha (DM) (Chracterised by chronic elevation of blood glucose), caused by deficiency of Insulin, if Regarding this study, for the biochemical parameters, 5 ml of

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S2 Singh, et al.: Study of physiological variation in serum insulin level and blood glucose level (fasting blood sugar and post prandial blood sugar) among young healthy individuals with special reference to Deha Prakriti venous blood was collected from the subjects in their hostels agni-bala (digestive and metabolic fire) in them. early in the morning during 6–8 AM. Serum was separated from the blood. Separation of the serum was done by During the study, it was also observed that serum insulin level centrifuging the blood sample at 3000 r.p.m. for 5–6 min and was almost same in Vata Prakriti (85.840 ± 1.22) individuals preserved in deep fridge at −20C till the estimation. Diametra and in Kapha Prakriti (85.846 ± 3.68) individuals. This ELISA Kit was used for insulin estimation. similarity in the level of insulin may be due to fluctuating level of insulin level in Vata Prakriti individuals. Followed ELISA protocol which was mentioned in Diametra ELISA Kit manual; then using a microtiter plate reader which Mean of FBS was observed maximum (95.30 ± 9.44) in was read at 450 nm and 630 nm wavelength. The test is Kapha Prakriti. performed on ERBA ELISA READER SEMI-AUTOMATIC MACHINE. The reagent kit was intended for the direct “in PPBS level in 1st h was observed maximum (131.11 ± 13.82) vitro” quantitative determination of serum insulin level. in Pitta Prakriti person.

PPBS after 1.5 h was observed maximum (110.58 ± 16.11) in Blood Sugar Estimation Kapha Prakriti individual.

Blood sugar was estimated by one touch glucometer. Fasting Similarly, PPBS after 2 h was observed maximum (94.80 ± blood glucose level was estimated in between 6 am and 8 am. 9.95) in Kapha Prakriti individual. Thereafter, for each volunteer, 75 g glucose was dissolved in 200 ml of water and was asked to drink. Postprandial blood Mean of FBS (95.30 ± 9.44) and PPBS level in 1.5 h (110.58 glucose level was tested after 1 h (post prandial blood sugar ± 16.11) and 2 h (94.80 ± 9.95) was observed maximum in st level in 1 h [PPBS1]), 1.5 h (PPBS after 1.5 h [PPBS2]), Kapha Prakriti. It may be due to nature of minimum physical and 2 h (PPBS after 2 h [PPBS3]). In between this period, and mental activity/behavior (Gambhirbuddhi) of Kapha all volunteers were asked not to eat or drink anything more. Prakriti persons.

It can be hypothesized that comparatively higher level of blood OBSERVATION AND RESULT sugar in Kapha Prakriti individual may be an important cause for more prevalence of NIDDM (T2DM/Madhumeha) in Kapha It has been observed that level of insulin was found maximum Prakriti individual, in comparison to Pitta and Vata Prakriti. (in upper range, 85.846 ± 3.68) in person having Kapha Prakriti [Table 1]. CONCLUSION Mean of fasting blood sugar (FBS) was observed maximum (95.30 ± 9.44) in Kapha Prakriti. On the basis of above findings, we can conclude that the biochemical and hormonal concentration of an individual st PPBS level in 1 h (PPBS1) was observed maximum (131.11 can be affected by Prakriti of an individual. Such type of ± 13.82) in Pitta Prakriti person. variation in the blood sugar level and insulin level was observed due to the effect of different level of agni and Bala PPBS after 1.5 h (PPBS2) was observed maximum (110.58 ± in different Prakriti person. The research may pave the path 16.11) in Kapha Prakriti individual. for prevention, treatment/management of various diseases, especially Madhumeha (DM), which is most dangerous Similarly, PPBS after 2 hour (PPBS3) was observed metabolic disorder in the present era. maximum (94.80 ± 9.95) in Kapha Prakriti individual. For the purpose of the present study, 89 volunteers were registered. Their Prakriti was determined/assessed by pro DISCUSSION forma.

Maximum level (85.846 ± 3.68) of insulin was observed It was observed that mean of FBS level (95.30 ± 9.44) was in person having Kapha Prakriti. It may be due to a good maximum in volunteers of Kapha Prakriti group. amount of bal (Mahabalah - physical and mental strength) in Kapha Prakriti person. On the basis of above finding of FBS (Empty stomach in morning) and PPBS after 1.5 hour and 2 hour after meal, was In pitta prakriti individual, it (Serum Insulinn) was found observed in maximum range in Kapha Prakriti individuals. in minimum range, i.e. 84.26 ± 3.07, and it may be due to This may be an important cause that Kapha Prakriti maximum and easily consumption and utilization of insulin individuals are more susceptible and prone to develop T2DM in pitta prakriti individuals, as they have good level of (Madhumeha).

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S3 Singh, et al.: Study of physiological variation in serum insulin level and blood glucose level (fasting blood sugar and post prandial blood sugar) among young healthy individuals with special reference to Deha Prakriti

Table 1: Table shows different Prakriti Group individuals Mean±SD Parameters V P K FBS in mg/dl 94.84±11.02 94.52±8.30 95.30±9.44 PPBS1 in mg/dl 126.52±15.04 131.11±13.82 129.77±19.5 PPBS2 in mg/dl 105.80±13.50 108.61±15.62 110.58±16.11 PPBS3 in mg/dl 89.32±11.30 92.68±12.60 94.80±9.95 Serum insulin mg/100 ml 85.84 0±1.22 84.26±3.07 85.84 6±3.68 FBS: Fasting blood sugar, PPBS1: PPBS level in 1st h, PPBS2: PPBS after 1.5 h, PPBS3: PPBS after 2 h, SD: Standard deviation

Whereas, in Pitta Prakriti individual, serum insulin level accessed on 2017 April]. was found in minimum range (84.26 ± 3.07). It indicates 9. Tripathi NS. Conceptual study of Vata Dosha -Controller that insulin is more utilized in glucose metabolism in pitta of body. Indian J Res Anvikshiki 2012;1:15-8. Available prakriti individuals. It may be an important cause that pitta from: http//www.onlineijra.com. [Last accessed on 2017 prakriti person develops least/less resistance to the insulin. April]. 10. Kumar SP, et al. Int J Res Ayurveda Pharm 2012;3. Available from: http://www.ijrap.net (Scopus). [Last REFERENCES accessed on 2017 April]. 11. Kumar CS, Tripathi NS. Study of seasonal variation in 1. Available from: http://www.who.int/mediacentre/ different Prakriti persons WSR to S. Urea. Int J Gen Med factsheets/fs138/en. [Last accessed on 2017 April]. Pharm 2013;2:23-8. Available from: http://www.iase.us. 2. Guyton A, Hall J. Text Book of Medical Physiology. [Last accessed on 2017 April]. 11th ed. Philadelphia: Publisher Elsevier Inc.; 2008, 12. Tripathi NS, et al. Correlative study of Dehik Prakriti 2015. in cases of Amavata with special reference to its 3. Kim EB, Susan MB. Ganong’s Review of Medical management. Indian J Res Anvikshiki 2012;6:17- Physiology. 23rd ed. New York: Publisher The McGraw- 21. Available from: http://www.onlineijra.com. [Last Hill Companies, Inc.; 2010. accessed on 2017 April]. 4. Chowkhambha Samskrit Series Office. Charak Samhita 13. Chowkhambha Samskrit Series Office. Charak Samhita English transalation by Dr. R.K. Sharma and Vaidya Sharirsthan, English translation by Dr. R. K. Sharma and Bhagvandash. 2nd ed. Varanasi: Chowkhambha Samskrit Vaidya Bhagvandash. 2nd ed. Varanasi: Chowkhambha Series Office; 1983. Samskrit Series Office; 1983. 5. Jain AK. Text Book of Physiology. 6th ed., Vol. 1 and 2. 14. Singh PK, Byadgi PS, Singh G, Tripathi NS. Impact Karol Bagh, New Delhi: Avichal Publishing Company; of season and constitution on lipid parameter. AYU 2012. 2013;34:77-80. 6. Tripathi NS. Concept of formation of prakriti. Indian J 15. Sthan AH. English translation by Professor K.R. Srikanth Res Anvikshiki 2011;1-5. Available from: http//www. Murthy. Varanasi: Chowkhambha Krishnadas Academy; onlineijra.com. [Last accessed on 2017 April]. 2009. 7. Tripathi NS. Conceptual study of development of 16. Chowkhambha Samskrit Series Office. Charak prakriti in Ayurveda. Indian J Res Anvikshiki 2011;23- Samhita Chikitsasthan. English translation by Dr. R. K. 7. Available from: http//www.onlineijra.com. [Last Sharma and Vaidya Bhagvandash. 2nd ed. Varanasi: accessed on 2017 April]. Chowkhambha Samskrit Series Office; 1983. 8. Chaudhary SK, Tripathi NS. Concept of homeostasis in Ayurveda. Indian J Res Anvikshiki 2012; 6:8-13. Available from: http//www.onlineijra.com. [Last Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S4 Prevention and management of Katishool through yoga and exercise

Ajay Kumar1, Vijay Kumar Rai2 1Reader, Department of Swasthavritta, Govt. Ayurvedic College and Hospital, Sampurnanand Sanskrit University, Varanasi, 2Lecturer, Department of Swasthavritta, Govt. Ayurvedic College and Hospital, Sampurnanand Sanskrit University, Varanasi

Abstract

Nowadays Katishool (lumber Spondylosis) is a common lifestyle disorder among all age group especially 40-70 years in society. Globally, nearly 40% people have pain at lower side at some point in their life. Poor or bad posture especially

REVIEW ARTICLE REVIEW forward slouch, wrong sleeping position, prolong sitting, sedentary mode of living, stress or strain due to heavy weight lifting or sports, excess bike riding and incorrect nutrition are the common cause of low back pain. Lumber Spondylosis is progressive and irreversible degenerative disorder of lumber vertebrae. Yoga Asanas and exercise can play a vital role for relieving pain and stiffness of back. To alleviate back pain one should practice Yoga Asanas and physical exercise regularly in proper method and proper guidance. Many research works have shown that various Yoga practices and physical exercises plays beneficial role in maintenance of spinal health and the management of Katishool.

Key words: Yoga, exercise, lumber Spondylosis, prevention, management

INTRODUCTION comprehends lumbar disc bulges, herniation, facet joint degeneration, disc degeneration, spinal canal stenosis, and owadays, Katishool (lumber spondylosis) vertebral bony overgrowths (osteophytes). is a common lifestyle disorder among Nall age group especially 40–70 years Lumber spondylosis is a spine condition that describes the in society; globally, nearly 40% people have natural degeneration of lower spine due to age and compression. pain at lower side at some point in their life. On both side of vertebra joint and disc made of soft tissue to Common cause of low back pain is poor or bad allow vertebra movement. The lower back of lumber spine is posture especially forward slouch, wrong sleeping to support and stabilize most of body’s weight. The repetitive position, prolong sitting, sedentary mode of living, incorrect turning, lifting heavy weight, and increasing body excess bike riding or traveling, stress or strain due weight are the reason that compresses vertebral discs resulting to heavy weight lifting or sports, and incorrect into tearing of discs, and displacement of discs. nutrition. Lumber spondylosis mean degenerative change such as osteoarthritis of vertebral joint and The constant pressure can cause the discs and joints to degenerating intervertebral discs in low back. gradually degenerate and possibly develop other spinal condition such as spinal stenosis. The formation of osteophyte Yoga and exercise play a key role in prevention can cause neural Forminal stenosis which will produce pain and management of back pain. Yoga and exercise due to pressure on spines and nerves. should be practiced regularly in proper method and guidance for alleviate back pain. Many research works have shown Yoga and exercise CAUSES AND RISK FACTORS OF play a beneficial role in the maintenance of spinal health and management of Katishool.[1] LUMBER SPONDYLOSIS There are many causes and risk factors for developing lumber spondylosis: COMMON PATHOLOGY Address for correspondence: Potential source of low back pain includes Ajay Kumar, Reader, Department of Swasthavritta, Govt. degeneration or injuries of intervertebral discs, Ayurvedic College and Hospital, Sampurnanand Sanskrit facet joint, vertebrae, neural structures, muscles, University, Varanasi E-mail: [email protected] ligaments, and fascia. Lumber spondylosis

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S5 Kumar and Rai: Prevention and management of katishool

1. Genetic - A specific type of gene HLA-B27 is more YOGA ASANAS responsible for developing lumber spondylosis 2. Age - Lumber spondylosis is a degenerate condition that Yoga Asana is a natural technique that focuses on controlled develops more common in older age (40–70 years) breathing through various body postures[5]. Many of the 3. Lifestyle - Certain lifestyle habit such as lack of exercise, postures in Yoga Asanas bring certain muscles flex, while sedentary life, and smoking is contributing risk factors other stretch is promoting relaxation and flexibility in the for developing Katishool muscles, joints, and spine and strengthen the muscles of the 4. Obesity - Overweight put extra load on lumber joints of back. back region, progressing lumber spondylosis due to bear and tear of the lumber region A list of best Yoga Asanas and other component are useful for 5. Injury - Spinal injury due to fall or accident leads to back pain as given below: dislodgement of vertebral joints or discs causing lumber 1. Tadasana spondylosis 2. Trikonasana 6. Other cause - Prolong sitting in abnormal position, more 3. Ardha Kati chakrasana biking, traveling, etc 4. Ushtrasana 7. Unhealthy diet - Continuous deficiencies of calcium 5. Ardh Matsyendrasana and Vitamin D in the diet may lead to degeneration 6. Marjariasana spines. 7. Bhujangasana 8. Makarasana 9. Dhanurasana SYMPTOMS OF LUMBER SPONDYLOSIS 10. Vipreet Naukasana 11. Uttanpadasana Initially, some patients suffering from lumber spondylosis do 12. Matsyasana not have symptoms. However, when symptoms do appear,[2] 13. Dhyan (meditation) they can notice the following symptoms: 14. Anulom Vilom Pranayama. • Back pain and stiffness in morning • Sitting prolong time increase pain We can select some Asanas according to the condition of • Worsening pain after repeated movement such as lifting the back pain and the deformities of the spine, and advice and bending the patient for regular practice of selected Asanas. If the • Regional tenderness deformities of spine have been noticed then physician advice • Pain of back may be radiate into legs is necessary[6]. Muscular activities such as stretching and • Numbness and tingling sensation in the limbs flexing increases blood flow with nutrients, toxins to flow • Weakness of affected limb due to nerve compression out, and overall nourishment of the muscles and soft tissues • Loss of bladder or bowel control (may be possible only in lower back. Meditation and Anulom Vilom Pranayama are in very advanced stage). also useful in the management of lower back pain. Meditation reduces stress and enhances mood. These mental benefits play an important role in reduce back pain. PREVENTION AND MANAGEMENT OF LOW BACK PAIN These Asanas are helpful in removing strain from the back and give strength and flexibility to the back[7]. Its bring back Practices of some Yoga and exercises in a controlled[3], elasticity to the back and remove stiffness and relieves pain progressive and under expert guidance, have many benefits from back region[8]. Its give strength the back muscles and including: good stretch to the ligaments and nerves, which provide • Strengthening the muscles of spine, removing pressure flexibility to the spine and make it more supple and healthy. from the spinal discs and facet joint • Relieving stiffness and improving mobility, improving range of motion and overall mobility EXERCISE • Improving circulation to better distribute nutrient through body, including to the spinal disc In spite of this Yoga, there are many stretching and twisting • Some beneficial hormones like endorphin can relieve exercises, which are beneficial in preventing and managing pain naturally. Endorphins can reduce the pain and can back pain. Some of the important stretching and twisting also elevate the mood and allow the mind to find a calm exercises for back pain are given as below: and meditative state.[4] 1. Hamstring stretch exercise

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2. Legs up the wall exercise function. Both Yoga and exercise are excellent nondrug 3. Spine stretching exercise approaches for prevention and management of low back pain. 4. Spine twisting right and left exercise 5. Twisting the spine forward and backward. REFERENCES Some of exercises are similar to Yoga in doing method and beneficial effect. The purpose of doing back stretches and 1. Murthy BA. Nirogam-Ayurvedic Treatment for Lumber spine twist is multifaceted. These are essential to maintain Spondylosis; 2015. Available from: www.nirogam.com/ mobility, joint health, sustain a good posture, and normalize ayurvedic-tretment-lumber-spondylosis. forces on discs.[9] Back stretches and spine twist will also 2. Exercise for Lower Back Pain Relief-Reviewed by maintain the flexibility of the spinal ligament, muscles, and Melissa Conrad Stoppler, MD. Available from: http:// fascia. www.onhealth.com. [Last accessed on 2017 Mar 03]. 3. Gopez JJ. Exercise Back Pain. Available from: http:// www.spine-health.com. [Last updated on 2017 Nov 10]. CONCLUSION 4. Available from: http://www.bigbackpain.com-2004- 2012. [Last accessed on 2018 Mar 27]. Yoga and exercise are the most effective ways of preventing, 5. Available from: http://www.physiotherapytreatment. managing and treating low back pain or chronic back pain. com-by Prodyut Das. [Last accessed on 2018 Mar 27] Strengthening muscles that support the spine with Yoga 6. Lumber Spondylosis: Causes, Symptoms and Treatment and exercise can prevent, reduce and eliminate lower back By Emily Lunardo. Available from: http://www. pain in some cases, the core muscles are muscles of the belmarrahealth.com. [Last accessed on 2017 May 08]. back, the abdomen, and buttocks, which work together 7. Rao MV. Swasthavritta. Varanasi: Chaukhambha support the spine. The core muscles help maintain normal Orientalia; 2017. p. 20117. posture and stabilize the spine Yoga and exercise to improve 8. Rai VK Sachitra Swasthavritta Vigyan. 1st ed. New strength, endurance, and coordination of the core muscles. Delhi: Chaukhambha Publication; 2009. Yoga and exercise play an important role in prevention and 9. Singh R. Swasthavritta Vigyan. Revised Edition. New management of low back pain. Both are effective as standard Delhi: Chaukhambha Pratishtan; 2009. physical therapy for prevention and treating moderate to severe chronic back pain. A carefully adapted set of Yoga and exercise practiced under guidance of well-trained Yoga instructor. These may help reduce back pain and improve Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S7 Antimicrobial study of Nagar-Ativishadi yoga in childhood Atisara (diarrhea): A review

P. S. Upadhyay, Ajeet Singh Yadav Department of Kaumarbhritya/Balrog, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

Atisara is very common disease in children, and it is well-described in almost all textbooks of Ayurveda. The description about the disease Atisara clearly correlates with diarrhea. However, a number of drugs/recipes in different textbooks of Ayurveda are mentioned for the treatment of Atisara, it is difficult to decide which one drug

REVIEW ARTICLE REVIEW is more effective in particular dosha specific Atisara. Nagar-Ativishadi yoga is described in Chakradatta, Vrind madhav, and Bhaishajya Ratnavali for the management of different types of Atisara in children. Nagaradi yoga contains five components, i.e., Nagar, Ativisha, Mustaka, Indrayava, and Balaka. It is used for the treatment of all types of Atisara in children. This literary review article shows antimicrobial activity against various microorganism which causes diarrhea in children.

Key words: Antimicrobial activity, Atisara, childhood diarrhea, dosha, Nagar-Ativishadi yoga

INTRODUCTION DEFINITION OF DIARRHEA (WHO)

iarrhea is most frequent gastrointestinal Diarrhea is defined as the passage of three or more loose or disorder in childhood, and it causes liquid stools per day. Frequent passing of formed stools is Da large proportion about (9%) of not diarrhea, nor is the passing of loose, “pasty” stools by childhood death. It is second most cause of breastfed babies. death in children, and approximately 0.71 million death occur per year globally. Global mortality may be decline rapidly, but the CAUSATIVE AGENT overall incidence of diarrhea has only decline from 3.4 to 2.9 episodes per-child year in About 70% of cases of acute gastroenteritis in children are past two decades. The decline in diarrheal caused by viruses such as rotaviruses, noroviruses, and mortality is the result of preventive rotavirus adenoviruses. About 40% of cases of acute diarrheal illness vaccination, improved case management in the first 5 years of life are caused by rotaviruses, while a of diarrhea, improved nutritional status of further 30% are caused by other viruses, mainly noroviruses, children and widespread home, and hospital- and adenoviruses. In about 20% of affected children, a bacterial based oral rehydration therapy. Early and pathogen can be identified in the stool (Campylobacter Jejuni, repeated episodes of diarrhea among young Yersinia, Salmonella, Shigella, Pathogenic Escherichia coli, children can be associated with malnutrition, micronutrient deficiency, and significant deficit or Clostridium difficile). Parasites are the cause in fewer than in psychomotor and cognitive development.[1] Address for correspondence: Dr. Ajeet Singh Yadav, Department of Kaumarbhritya/ Balrog, Faculty of Ayurveda, Institute of Medical MATERIALS AND METHODS Sciences, Banaras Hindu University, Varanasi – 221 005, Uttar Pradesh, India. This literary survey was conducted with the help E-mail: [email protected] of several important Ayurvedic and Modern textbook, research paper, and journal to collect Received: 09-01-2018 information on Nagar-Ativishadi yoga, which is Revised: 13-02-2018 used in the management of childhood Atisara Accepted: 18-02-2018 (diarrhea).

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S8 Upadhyay and Singh: Antimicrobial study of Nagar-Ativishadi yoga: A review

5% (Giardia lamblia, Cryptosporidium parvum, Entamoeba MANAGEMENT histolytica, and others). Oral Rehydration

TYPES OF DIARRHEA Oral rehydration is recommended for patients with clinically manifest mild dehydration (>3% weight loss). Acute Diarrhea Oral rehydration with hypotonic rehydration solution is the treatment of choice. It is applicable, and successful, in 90% Acute diarrhea is the presence of three or more stool, which is of children with mild to moderate dehydration. loose and watery in nature within 24 h. These acute episodes subside within 7 days. Pharmacotherapy

Chronic Diarrhea Antibiotics Most episodes of diarrhea are self-limiting and do not require It is defined as an insidious onset diarrhea of more than any drug therapy except in few situations. Antibiotics are 2 weeks duration in children and more than 4 weeks in the not recommended for routine treatment of acute diarrhea in adult. It is a common problem in children. children. In acute diarrhea, antimicrobials are indicated in bacillary dysentery, cholera, amebiasis, and giardiasis.[2] Persistent Diarrhea Antisecretory It is an episode of diarrhea, of presumed infectious etiology, Racecadotril is an enkephalinase inhibitor that reduces which start acutely but last for more than 14 days. pathologically increased secretion within a few hours in diarrhea of either viral or bacterial origin. Dysentery Probiotics When bloody diarrhea accompanied with complaint of Microorganisms that exert beneficial effects on human pyrexia, tenesmus, suprapubic discomfort, and cramps health when they colonize in the bowel have been proposed [2] abdominal pain, it is known as dysentery. as adjunctive therapy in the treatment of diarrhea. Several microorganisms such as Lactobacillus rhamnosus, Complications Enterococcus faecium, and Saccharomyces boulardii have been shown to some efficacy in reducing the acute diarrhea. The possible complications of an acute diarrheal illness include dehydration, metabolic acidosis, impaired consciousness, convulsions, circulatory shock, and prerenal PREVENTION azotemia. 1. Adequate breastfeeding: Mother’s milk protects against infection, including acute infectious enteritis Investigation 2. Maintain General hygienic measures, i.e., hygienic handling of food: Bacterial infections acquired through Stool R/M (pH, reducing substance, fungal hyphae, occult food usually arise because of the consumption of blood, ova, and cyst), stool C/S, blood tests are complete blood incompletely cooked meat (Yersinia, Campylobacter, and count, acid-base status, glucose, electrolytes, creatinine, and Salmonella), raw eggs (Salmonella), and unpasteurized blood urea nitrogen. milk (enterohemorrhagic E. coli infections) 3. Rotavirus vaccination. Differential-diagnostic studies

Ultrasonography or another type of imaging study is indicated ANTIMICROBIAL ACTIVITIES OF NAGAR- if there is clinical suspicion of intussusception. Endoscopic ATIVISHADI YOGA [TABLES 1-5] procedures for the obtaining of biopsy samples are reserved for special situations, e.g. in patients with an underlying As per the previous antimicrobial studies, the antimicrobial illness to exclude other possible diagnoses, such as chronic effect of each component of Nagar-Ativishadi yoga has been inflammatory bowel disease tabulated in [Tables 1-5].

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S9 Upadhyay and Singh: Antimicrobial study of Nagar-Ativishadi yoga: A review

Table 1: Nagar (Zingiber officinale) Reference Name of bacteria and fungus In vivo or in vitro Result Science direct food and P. aeruginosa, Salmonella In vitro This drug is effective against chemical toxicology.[3] typhimurium, E. coli, C. albicans these bacteria and fungus. 46 (2008) p. 409‑420 IOSR‑JPBS[4] E. coli, Proteus sp. Staphylococci, In vitro This drug is proved by in vitro Volume 9, Issue Streptococci, S. aspergillus sp. study against these bacteria 5 (September‑October and fungus. 2014), p. 124‑129 International Journal of E. coli, Salmonella sp. V. cholerae, In vitro This drug is having Science, Environment and P. aeruginosa, S. aureus, antibacterial property against Technology.[5] Vol. 3, 2014, Klebsiella spp. the listed bacteria. p. 867‑871 Z. officinale: Zingiber officinale, P. aeruginosa: Pseudomonas aeruginosa, S. typhimurium: Salmonella typhimurium, E. coli: Escherichia coli, C. albicans: Candida albicans, V. cholera: Vibro cholera, P. aeruginosa: Pseudomonas aeruginosa, S. aureus: Staphylococcus aureus

Table 2: Ativisha (Aconitum heterophyllum) Reference Name of bacteria In vitro or in vivo Result IJNPR[6] Vol. 2 (4), S. aureus, B. subtilis, In vitro In vitro study proves antibacterial property. Dec 2011 Aspergillus IJAR[7] S. aureus, B. subtilis, In vitro The plant is effective against the listed bacteria Vol. 2 Issue 7 2014 E. coli JEIMC[8] Vol. 23 S. typhi P. aeruginosa In vitro This drug is having antibacterial activity. Issue 6 2008 A. heterophyllum: Aconitum heterophyllum, S. aureus: Staphylococcus aureus, B. subtilis: Bacillus subtilis, E. coli: Escherichia coli, S. typhi: Salmonella typhi, P. aeruginosa: Pseudomonas aeruginosa

Table 3: Musta (Cyperus rotundus) Reference Name of bacteria In vitro or in vivo Result American Journal of Pharmacy and E. coli, P. aeruginosa, In vitro This drug has antibacterial property Pharmaceutical Sciences.[9] Vol. 2, B. subtilis, S. aureus. against these bacteria. 2015 International Journal of Current S. aureus, B. subtilis. In vitro This drug is effective against the Microbial Applied Science.[10] E. coli, Streptococcus listed bacteria. Vol. 3, 2014 Scholar Research Library Der E. coli, P. aeruginosa In vitro In vitro study proves antibacterial Pharmacia Lettre.[11] Vol. 3, 2011 C. albicans A. niger property against these organism. C. rotundus: Cyperus rotundus, E. coli: Escherichia coli, P. aeruginosa: Pseudomonas aeruginosa, B. subtilis: Bacillus subtilis, S. aureus: Staphylococcus aureus, C. albicans: Candida albicans, A. niger: Aspergillus niger

ATISARA Brihatrayi. Acharya Dalhana on his commentary on Sushruta samhita stated that passing of watery stools in increased Atisara (diarrhea) has been much detail described in the quantity is a characteristic feature of Atisara. ayurvedic text, but not in term of children. It is of six types, i.e., Vataja, Pittaja, Kaphaja, Sannipataja, Bhayaja, and Shokaja (Amaja). However, certain specific disorder in which SYNONYMS OF ATISARA diarrhea is the major symptoms have been reported in ancient ayurvedic literature such as Ksheeralasaka, and Graha roga The synonyms of atisara are Bhinnavarcha and Udaramaya. (Putana, Sheet putana, and Andha putana).

ETIOLOGY OF ATISARA[16] DEFINITION OF ATISARA The etiology of Atisara is as follows: Excess intake of Guru, Atisara is the excessive passage of liquid through the anus. Snigdha, Ushna drava, and Sheeta food items. intake of The description of Atisara is available in each textbook of incompatible food items, taking of food in Ajirna, Adhyasana,

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Table 4: Indrayava (Holarrhena antidysenterica) Reference Name of bacteria In vitro or in vivo Result Journal of Pharmacy Research.[12] E. coli, S. fleneri, In vitro This drug effective against these Vol. 6 , 2013 S. enteritidis bacteria. V. cholerae Natural Product An Indian Journal.[13] S. aureus, E. coli, In vitro This drug effective against these Vol. 5 (4), 2009 Pseudomonas sp., bacteria. pp ‑ 232‑234 Salmonella sp., and V. cholera The Pharma Innovation Journal.[14] E. coli In vitro This drug show antibacterial activity. Vol. 4, 2015 S. typhi S. aureus H. antidysenterica: Holarrhena antidysenterica, E. coli: Escherichia coli, S. fleneri: Shigella fleneri, S. enteritidis: Salmonella enteritidis, V. cholera: Vibro cholera, S. aureus: Staphylococcus aureus, S. typhi: Salmonella thyphi, S. aureus: Staphylococcus aureus

Table 5: Balaka (P. odorata) Reference Name of bacteria In vitro or in vivo Result American Journal of S. aureus, E. coli, A. flavus, In vitro This drug show antibacterial Phytomedicine and Clinical A. niger, activity against these bacteria and Therapeutics.[15] Vol. 3 (1) 2015 C. albicans fungus. Pavonia odorata, S. aureus: Staphylococcus aureus, E. coli: Escherichia coli, A. flavus: Aspergillus flavus, A. niger: Aspergillus niger, C. albicans: Candida albicans and Vishmasana. Drinking of contaminated water; taking of Pittaja Atisara excess alcohol; and suppression of natural urges, suffering from Krimi. In this Atisar stool is yellowish, greenish, or blackish in color, with foul smell and burning sensation, thirst, sweating, and fainting. TYPES OF ATISARA Kaphaja Atisara There are broadly six types of Atisara[17] 1. Vataja Atisara In this Atisar stool is unctuous, white, slimy, thready, and 2. Pittaja Atisara heavy stool with mucus. Horripilation, nausea, and tenesmus 3. Kaphaja Atisara are present. 4. Sannipataja Atisara 5. Shokaja Atisara 6. Amaja Atisara. Sannipataja Atisara

Due to imbalance of all doshas in Sannipataja Atisara, stool [18] may be yellowish, greenish, bluish, or reddish in color and it PRODROMAL SYMPTOMS may be painful or painless. The prodromal symptoms are Hridaya, Nabhi, Payu, Udar and Kukshitoda (Pricking type sensation in Hridaya, Nabhi, Payu, Shokaja Atisara Udar, and Kukshi pardesh), Gatraavasada (General malaise), Vitasanga (constipation), Anilsannirodha (non-elimination of In this Atisar signs and symptoms are similar to Vataja flatus), Adhman (distention of abdomen), and Avipaka (indigetion). atisara.

Amatisara SIGNS AND SYMPTOMS OF DIFFERENT TYPE OF ATISARA[19] In condition of Amatisara, stool is passed with difficulty, is of various colors and large in number. Various authors have Vataja Atisara enumerated six types of Atisara (Vataja, Pittaja, Kaphaja, Sannipataja, Shokaja, and Bhayaja) but with a slight variation In this Atisara stool is blackish in color, rough, frothy, small in respect to Bhayaja Atisara which has been replaced with in amount and with pain in abdomen. Amaja Atisara by Sushruta. Charaka has included Amaja

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S11 Upadhyay and Singh: Antimicrobial study of Nagar-Ativishadi yoga: A review atisara in Sannipataja-Atisara because grief and fear both Action: Tridosh Shamak have relation with psyche, so the description of Sushruta Use: Jwar, Atisara, Deepan, and Raktarsha seems to be more logical. 5. Balaka: [24] Rasa: Madhur, Tikta, Guna: Laghu, Ruksha Virya: Sheeta Keeping in with the line of treatment Charaka has divided each Atisara in Ama and Pakva. It may be presumed Doshika Action: Kapha–Pitta Shamak, Use: Jwar, that due to this reason Charaka has not mentioned Amaja Atisara, and Trishna. Atisara separately. Few texts have mentioned Raktaja Atisara separately also, which has been said to be caused by consumption of Pitta enhancing diet in Pittaja Atisara. CONCLUSION

Atisara Nivriti Lakshana Atisara (Diarrhea) is one of the most commonly occurring diseases in children, and it causes a large proportion of The symptoms of recovery from Atisara are- Proper childhood death. This review drug (Nagar-Ativishadi yoga) [25] [26] elimination of urine, flatus, and stool, enhancement of Agni is well described in Chakradatta, Vrindamadhav, and [27] and feeling of lightness. Bhaishjya Ratnavali for the management of different types of Atisara in children. It has Deepan, Pachan, Grahi, Krimighna, and Atisaraghna property and this drug also Chikitsa Sutra have antimicrobial activity against those microorganism which causes diarrhea in children. Hence, due to all these Atisara chikitsa is planned after seeing the sama and nirama property, Nagar-Ativishadi yoga is used in childhood Atisara avasta of the dosa. Therapies which are mainly of deepana, (diarrhea). pachana, and langhana should be adopted in the ama avasta of the disease. In the niramavasta, the drugs which have stambhana properties are to be selected. Acharya Sushruta, REFERENCES Bhava Prakasha, and Bhaishaja Ratnavali all have stated that since the treatment of atisara is not apart from the treatment 1. Kliegman RM. Nelson Textbook of Pediatrics. First of ama and pakva, hence in all kinds of atisara signs and South Asia edition., Vol. 02. Chap. 340. New Delhi: symptoms of ama and pakva should be determined first. Published by Elsevier; 2016. p. 1855. 2. Ghai OP, Paul VK, Bagga A, Ghai Essential Pediatrics. th Pathya 8 ed. Ch. 11. New Delhi: CBS Publishers and Distributors Pvt. Ltd.; 2013. p. 291-9. The path ya of Atisara is as follows: Mand, vilapi, bilva, 3. Ali BH. Some phytochemical, pharmacological and dhanyaka, mudga, daliya, goat-milk, langhna, sleep, rest etc. Toxicological property of ginger. Sci Direct Food Toxicol 2008;46:409-20. 4. Gupta SK. Medicinal property of Zingiber officinale Apathya Roscoe. IOSR J Pharm Biol Sci 2014;9:124-9. 5. Islam K. Antimicrobial activity of ginger (Zingiber The Apathya of Atisara is as follows: Pea, Nishpava, Barley, Officinale) extracts against food-borne pathogenic heavy and unctuous food, overeating, exertion, smoking, etc. bacteria. Int J Sci Environ Technol 2014;3:867-71. 6. Shrivastav N. In vitro antimicrobial acyivity of areal parts extracts Aconitam heterophyllum. Indian J Nat PHARMACOLOGICAL ACTION OF Prod Resour 2011;2:504-7. NAGARADI YOGA AS FOLLOWS 7. Yoirentomba M. Antibacterial property of Aconitum heterophyllum root alkaloid. Int J Adv Res 2014;2:839-44. 1. Nagar: [20] Rasa: Katu, Guna: Laghu, Snigdha, Virya: 8. Ahmed M. Norditerpenoid alkaloids from roots of Ushna, Vipaka: Madhur Aconitum heterophylum with antibacterial activity. Doshik Action: Kapha-Vata, Shamaka, Use: Rochan, J Enzyme Inhibit Med Chem 2008;23:1018-22. Pachan, and Grahi 9. Ahmed S. Antimicrobial activity and cytotoxicity of 2. Ativisha: [21] Rasa: Tikta, Katu,and Virya: Ushna, ethanolic extract of Cyperus rotundus. Am J Pharm Vipaka: Katu Pharm Sci 2015;2:1-13. Doshika Action: Kapha-Pitta Shamak, Use: Aam, 10. Prasad MP. Analysis of antimicrobial compounds in Atisara, Visha, and Kriminashak Cyperus rotundus and against Azadirachta indica human 3. Musta: [22] Rasa: Katu, Tikta, and Kashaya, Virya: Sheeta pathogens. Int J Curr Microbiol Appl Sci 2014;3:206-10. Doshika Action: Kapha-Vata Shamak, Use: Deepan, 11. Sharma SK. Antimicrobial investigations on rhizomes Pachan, Grahi, and Krimighna of Cyperus rotundus Linn. Sch Res Lib Pharm Litt 4. Indrayava: [23] Rasa: Katu, Virya: Sheeta, Doshika 2011;3:427-31.

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12. Sinha S. Evaluation of phytochemical and Published By Chaukhambha Bharati Academy; 2010. p. 13. pharmacological aspects of Holarrhena antidysenterica. 21. Chunekar KC. Commentary on Bhavaprakash Nighantu J Pharm Res 2013;6:488-92. of Bhava Mishra. Revised and Enlarged Edition Varanasi: 13. Joice M. Antibacterial activity of seed and bark extracts Published By Chaukhambha Bharati Academy; 2010. of Holarrhena antidysenterica. Nat Prod Indian J p. 122. 2009;5:232-4. 22. Chunekar KC. Commentary on Bhavaprakash Nighantu 14. Shrivastav N. Antibacterial activity of kutaj (Holarrhena of Bhava Mishra. Revised and Enlarged Edition Varanasi: antidysenterica Linn.) in childhood diarrhea: In vitro Published By Chaukhambha Bharati Academy; 2010. study. Pharm Innov J 2015;4:97-9. p. 73. 15. Rayar A. Anti-microbial and anti-inflammatory activity 23. Chunekar KC. Commentary on Bhavaprakash Nighantu of bioactive components of Pavonia odorata Wild. Am J of Bhava Mishra. Revised and Enlarged Edition Varanasi: Phytomed Clin Ther 2015;3:79-87. Published By Chaukhambha Bharati Academy; 2010. 16. Ambikadatta S. Ayurvedtatvasandipika Hindi p. 233. commentary on Sushruta Samhita, Part-II. Ch. 40. 24. Sharma PV, Sharma GP. Kaiyadeva-Nighantuh Varanasi: Chaukhambha Sanskrit Sansthan; 2012. p. 272. (Pathyapathya -Vibodhaka). Varanasi: Published by 17. Ambikadatta S. Ayurvedtatvasandipika Hindi Chaukhamba Orientalia; 2009. p. 253. commentary on Sushruta Samhita, Part-II. Ch. 40. 25. Indradeva T. “Vaidha Prabha” Hindi Commenatry Varanasi: Chaukhambha Sanskrit Sansthan; 2012. on Chakradatta, Edited by Prof. Ramanath Dwivedi. p. 274. Balroga Chikitsa 64/33. Varanasi: Chaukhambha 18. Ambikadatta S, Ayurvedtatvasandipika Hindi Sanskrita Bhawan; 2010. commentary on Sushruta Samhita, Part-II. Ch. 40. 26. Premvati T. Vrindamadhava of Siddhyoga. 1st ed. Siddha Varanasi: Chaukhambha Sanskrit Sansthan; 2012. Yoga (Vrindmadhav) 66/23. Varanasi: Published by p. 275. Chaukhambha Vishvabharati; 2007. 19. Ambikadatta S, Ayurvedtatvasandipika Hindi 27. Ambikadatta S, ‘Vidyotini’ Hindi commentary on commentary on Sushruta Samhita, Part-II. Ch. 40. Bhaisajya Ratnawali. Balrogadhikar 71/52. Varanasi: Varanasi: Chaukhambha Sanskrit Sansthan; 2012. Published by Chaukhambha Sanskrit Sansthan; 2012. p. 275-8. 20. Chunekar KC. Commentary on Bhavaprakash Nighantu of Bhava Mishra. Revised and Enlarged Edition Varanasi: Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S13 Phytochemical study of Drakshadi yoga extracts W.S.R. Kasa

P. S. Upadhyay1, Amber Sahu1, B. K. Sharma2 1Department of Kaumarbhritya/Balroga, Faculty of Ayurveda, Banaras Hindu University, Varanasi, Uttar Pradesh, India, 2Department of Mycology and Plant Pathology, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

Aim of study: Phytochemical evaluation of the efficacy of Drakshadi yoga in the children suffering from Kasa Drakshadi Yoga which contains Draksha, Pippali, Haritaki, and Vasa. Material and method: All these drugs have been described to have anti-cough properties and antimicrobial properties in different texts. Observation and result For the phytochemical study, the dried samples of contents of Drakshadi Yoga were re-suspended in ORIGINAL ARTICLE ORIGINAL high-performance liquid chromatography grade ethanol. In phytochemical study, out of the 7 phenolic standards used, Draksha contained 4 compounds, whereas vasa and Haritaki contains 5 compounds while Pippali contains 6 phenolic compounds, it means Drakshadi yoga having high antioxidant property.

Key words: Antioxidant property, cough, high-performance liquid chromatography, Kasa, phytochemical study

INTRODUCTION there has been increased interest in the investigation of natural products as a source of new antibacterial agents. Several espiratory complaints are well-known experimental studies have contributed scientific evidence for clinical presentation in the modern the pharmacological effects of medicinal plants observed in medical science. They are classified under folk medicine.[11] Although to achieve the best result out of this R holistic approach, it is essential to understand completely the the broader heading of respiratory tract disorders, which contains group of different symptoms basic fundamentals and also the approach of that system and has and diseases. In developing and even developed to prove these drugs on the standard of scientific parameters. countries, pediatric outdoor patients department has more than 50% of patients having respiratory tract complaints,[1,2] in recent years, there has MATERIALS AND METHODS been an extraordinary increase of incidence related to respiratory system. According to The test plants were identified and authenticated in the National Center for Health Statistics, 62 million Department of Botany, Banaras Hindu University, Varanasi, cases of common cold and cough occurs each with the voucher specimen no. as given: year. Cough is the fifth most common symptom 1. Adhatoda vasica Nees. (Voucher specimen No. Acanth. for which patients seek medical care. Kasa has 2017/4) been described under various categories in the 2. Piper longum L. (voucher specimen No. Piper 2017/2) classics of Ayurveda - as independent disease,[3,4] 3. Terminalia chebula Retz.(voucher specimen No. symptom[5] complication,[6] and sequel. Kasa Combret. 2017/1) is a common upper respiratory tract ailment 4. Vitis vinifera L. (Voucher specimen no Vita. 2017/1). prevalent nowadays, and it is increasingly annoying and irritating the individual in his The phytochemical study was conducted in the Department routine activity. Nonjudicious use of antibiotics of Mycology and Plant Pathology, Institute of Agricultural and corticosteroids[7] in contemporary system Sciences, BHU, Varanasi. of medicines during present era has led to the iatrogenic suppression of host immunity and birth of multidrug-resistant traits of pathogens.[8] This Address for correspondence: phenomenon, in turn, results in the recurrence Dr. Amber Sahu, Department of Kaumarbhritya/Balroga, of respiratory tract infection.[9] The developing Faculty of Ayurveda, Banaras Hindu University, Varanasi countries dependent on traditional medicine for – 221 005, Uttar Pradesh, India. a variety of diseases.[10] In the past two decades, E-mail: ambersahuimsbhu2gmail.com

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Table 1: Concentration of the phenolic compounds in the four plants Phenolic compounds Draksha Vasa Pippali Haritaki Gallic acid 71.74 µg/ml 24.02 µg/ml 23.54 µg/ml 313 µg/ml Fumaric acid 28.07 µg/ml 22.2 µg/ml 5.03 µg/ml 153 µg/ml P‑amino Benzoic acid 13.57 µg/ml ‑ 5.4 µg/ml 67.41 µg/ml Syringic acid ‑ 11.1 µg/ml 6.6 µg/ml ‑ Succinic acid ‑ 248.42 µg/ml 15.80 µg/ml 400 µg/ml Ferulic acid ‑ ‑ ‑ 22.37 µg/ml P‑ Coumaric acid 230.93 µg/ml 15.69 µg/ml 1.6 µg/ml ‑

For the study, drug extract was prepared in the Department of OBSERVATION AND RESULT [TABLE 1] Dravyaguna, IMS BHU by the Soxhlet method of extraction ethanolic extract of each drug was collected in a separate In phytochemical study, out of the 7 phenolic standards sterile vial and preserved at temperature 4°C. used, Draksha contains 4 phenolic compound, i.e., gallic acid, fumaric acid, P-aminobenzoic acid, and P-coumaric The dried samples were re-suspended in high-performance acid whereas Vasa contains 5 phenolic compounds, i.e., liquid chromatography (HPLC) grade ethanol for HPLC gallic acid, fumaric acid, syringic acid, succinic acid, and analysis. Shimadzu LC-10A (Japan) was used that was P-coumaric acid and Pippali contains 6 compounds as shown equipped with the dual pump LC-10A binary system, in the table. Ferulic acid was detected only in Haritaki, and ultraviolet detector SPD-10A, and Phenomenex (Torrance, syringic acid was not detected in Haitaki. Five phenolic USA) C18 column (RP-Hydro, 4 µm, 250 mm × 4.6 mm). compounds, i.e., gallic, fumaric acid, P-amino benzoic acid, Shimadzu Class VP series software was used to integrate the succinic acid, and ferulic acid, were detected in Haritaki. data separation of phenolics was achieved with acetonitrile/ water (1:1 v/v) containing 1% acetic acid in a linear gradient program (Singh et al., 2009). The solvent flow rate DISCUSSION AND CONCLUSION was 1.0 ml/min. In phytochemical study, out of the 7 phenolic standards The standards used for the study are given below: used, draksha contained 4 phenolic compounds, i.e., gallic acid, fumaric acid, P-aminobenzoic acid, and P-coumaric Standard RT Area (A1) acid whereas Vasa contained 5 phenolic compounds, i.e., gallic acid, fumaric acid, syringic acid, succinic acid, and Gallic acid 3.668 42990104 P-coumaric acid and Pippali contained 6 compounds as Fumaric acid 3.851 14086081 shown in the table. Ferulic acid was detected only in Haritaki, P‑Aminobenzoic acid 5.409 43953033 and syringic acid was not detected in Haitaki. Five phenolic Syringic acid 7.434 46304381 compounds, i.e., gallic, fumaric acid, P-aminobenzoic acid, Succinic acid 10.343 1759363 succinic acid, and ferulic acid, were detected in Haritaki. The beneficial effects derived from phenolics compounds Ferulic acid 10.884 67716478 have been attributed to their antioxidant activity.[12] It means P‑coumaric acid 11.201 16724881 Drakshadi yoga has high antioxidant property.

Y×1000 Formula: µg/ml or µg/g of sample Z REFERENCES

Where Y = area of unknown sample (Vasa, Haritika, Pippali, 1. Eggenberger K. Les infections des voies respiratoiresles and Draksha) plus fréquentes chez ‘enfant dans la pratique ambulatoire. Respiratory tract infections mostfrequently seen in Z = Area of Known sample pediatric outpatient care. Ars Med 1993;83:24-40. 2. Kvaerner KJ, Nafstad P, Jaakkola JJ. Upper respiratory “X” = Symbol for multiplication morbidity in preschool children: A cross sectional study. Arch Otolaryngol Head Neck Surg 2000;126:1201-6. Match the retention time (RT ± 0.200) of the known sample 3. Acharya JT. Charaka samhita. Varanasi: Chaukhambha (standard) with your unknown sample and calculate the Sanskrit Sansthan; 2011. p. 433. concentration of the particular phenolic compound in your 4. Acharya JT. Susruta Samhita. Varanasi: Chaukhambha sample. Sanskrit Sansthan; 2012. p. 766

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5. Sastri R. Harita Samhita. Varanasi: Prachya Prakasan; 121. Philadelphia: Saunders Elsevier; 2008. p. 867. 1985. p. 232. 10. Gangoue-Pieboji J, Pegnyemb DE, Niyitegeka D. The 6. Sastri R. Harita Samhita. Varanasi: Prachya Prakasan; in vitro antimicrobial activities of some medicinal 1985. p. 230. plants from Cameroon. Ann Trop Med Parasitol 7. Guyton AC, Hall JE, Resistance of the Body to Infection: 2006;100:237-43. Immunity and Allergy, Textbook of Medical Physiology. 11. Nardi GM, Felippi R, Dalbo S. Anti-inflammatory 11th ed. Ch. 34. Philadelphia: W.B.Saunders Co.; 2008. and antioxidant effects of Croton celtidifolius bark. p. 439-50. Phytomedicine 2003;10:176-84. 8. Jacobs RF. Judicious use of antibiotics for common 12. Wright RJ, Cohen RT, Cohen S. The impact of stress as pediatric respiratory infections. Pediatr Infect Dis J a predictor of wheezing in infancy, a prospective study. 2000;19:938-43. Am J Respirat Crit Care Med 2002;165:358-665. 9. Buckley RH. Evaluation of the immune system. In: Behrman RE, Kliegman RM, Jenson HB, editors. Nelson’s Textbook of Pediatrics. 18th ed., Vol. 1. Ch. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S16 A review on meditational plants described in Ayurvedic classics having antidiabetic activity

Anjali Upadhyay1, Neha Chaudhary1, Ashwini Kumar Kushwaha2, Dev Nath Singh Gautam3 1Ayurvedic Pharmacy Laboratory, Rajiv Gandhi South Campus, Banaras Hindu University, Mirzapur, Uttar Pradesh, India, 2Department of Dravyaguna (RGSC), Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India, 3Department of Rasa Shastra, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

REVIEW ARTICLE REVIEW Abstract

Ayurveda an ancient system of medicine is derived from two words Ayu and Veda, “Ayu means “Live or longevity” and Veda means “Science.”Ayurveda is one of the oldest systems of medicine which is still practicing worldwide today. Ayurvedic drugs are consider as safe because drugs are used in this system of medicine is natural in origin and obtain from plants, animals, and minerals. This review focuses on plants which are useful in diabetes mellitus. In the present era, diabetes is a common and major problem, and it is a metabolic disorder occuring due to lack of insulin or insensitivity of insulin receptor. In Ayurvedic classic, several plants are described which are found effective in diabetes and are discussed in the present paper.

Key words: Ayurveda, diabetes, insulin, medicine, plant etc.

INTRODUCTION ETYMOLOGY

yurveda an Indian system of medicine The term diabetes mellitus is derived from Greek word primarily has two motives: To prevent diabetes which means “To go through.” Diabetes is Athe health of healthy individuals and a chronic metabolic disorder characterized by increased to cure the diseased one. In ayurvedic system level of blood glucose in the body due to improper of medicine, plants, animals, and minerals function of insulin. Insulin harmone is highly required to are a source of drugs and considers as safe as convert carbohydrate, starch, sugar, and other food into synthetic medicine used in modern system of energy. medicine.

About 25.8 million children and adults in TYPES OF DIABETES the United States are affected by diabetes mellitus, and it is a major problem in India Diabetes mellitus is two types: also. The percentage of diabetic patients is • Type-1: It is insulin-dependent diabetes, in which increasing rapidly in India. Demand of herbal pancreas produced little or no insulin and usually medicines is highly increasing in the past diagnosed in children, young adults and it appears in any few years because of their natural origin, low stage. cost of the product, and less side effect to the body. In Ayurveda and other traditionally Address for correspondence: used medicinal system, more than hundred Ashwini Kumar Kushwaha, Department of Dravyaguna medicinal plants are used in the treatment of (RGSC), Faculty of Ayurveda, Institute of Medical the diabetes mellitus. An expert committee Sciences, Banaras Hindu University, Barkachha, of the World Health Organization (WHO) Mirzapur-231001, Uttar Pradesh, India. is so much interested in the investigation Phone: +9415447658. of diabetes treatment method in Ayurveda E-mail: [email protected] system of medicine.[1]

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Table 1: List of some common plant found in india having antidiabetic activity Classical/Common name Botanical Name Family Part Used Bilva/Bael A. marmelos Rutaceae Fruit, Leaves Palaandu/Pyaja A. cepa Amaryllidaceae Whole plant Rason/Lahsun A. sativum Liliaceae Ripe bulbs Kalmegh A. paniculata Rutaceae Whole Nimba/Neem A. indica Meliaceae Whole plants Kuberaksha/Kantakikaranja C. bonducella Leguminosae Twak, Leaf, Flower Bimbi/Kundaru C. indica Cucurbitaceae Leaves Haridra/Haldi C.longa Zigiberaceae Rhizome Meshashringi/Gurmar G. sylvestre Asclepiadaceae Leaves Sakkarkand I. batatas Convolvulaceae Rhizome Jambu/Jamuna S. cumini Myrtaceae Fruit, leaf, stem bark Karvellaka/Karela M. charantia Cucurbitaceae Fruit, leaf Kadali/Banana M. paradisiacal Musaceae Seed, fruit Sursa/Tulsi O. sanctum Labiatae Dry leaf Bhumamalki P. amarus Euphorbiaceae Whole Kasthdaru P. longifolia Annonaceae Bark Bijaka/Indian Malabar P. marsupium Leguminoaceae Sara Methika/Methi T. foenum Papilionaceae Seed Guduchi T. cordifolia Menispermaceae Whole Pishach karpas/Devil cotton A. augustum Sterculiaceae Root Talispatra A. pindrow Pinaceae Root, leaf Shallaki B. serrata Burseraceae Gum, resin Kanchnaar/Orchid tree B. variegata Fabaceae Bark Amalaki E. officinalis Phyllanthaceae Fruit, seed, leaf Bhringraj E. alba Asteraceae Whole Aadhaki/Arhar C. cajan Fabaceae Leaf, seed, fruit Asvatha/Peepal F. religiosa Moraceae Bark Tea C. sinensis Theaceae Leaf Marsh barbel H. auriculata Acanthaceae Aerial part Madhuka/Mulethi G. glabra Fabaceae Root Anantmula H. indicus Asclepidiaceae Root Hapusa/Juniper berry J. communis Cupressaceae Dried berries Akshota/Walnut J. regia Juglandaceae Root, unripe fruit Tandula/Rice bran O. sativa Gramineae Root, coat seed Maruaka/Vantulsi O. vulgare Lamiaceae Leaf Kaidarya/Curry leaf M. koenigii Rutaceae Leaf, fruit juice Aamra/Mango M. indica Anacardiaceae Stem bark, leaf Karvi/Black cumin N. sativa Ranunculaceae Oil seed Bhallatak S. anacardium Anacardiaceae Fruit, nut Asvagola/Ispaghula husk P. ovata Plantaginaceae Seed, husk Erandakarkati/Papaya C. papaya Caricaceae Leaf Babhul A. Arabica Leguminosae Stem bark, fruit Ghritkumari A. barbadensis Asphodelaceae Gel, leaf Ashwagandha W. somnifera Solanaceae Root (Contd...)

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Table 1: (Continued) Classical/Common name Botanical Name Family Part Used Kanchnaar/Orchid tree B. purpurea Fabaceae Leaf Tailparna/Eucalyptus E. globulus Myrtaceae Leaf Kapas/Cotton G. herbaceum Malvaceae Root, bark, fruit Vyaghraeranda/Jatropa J. curcas Euphorbiaceae Leaf, seed, oil Katong laut C. ramiflora Fabaceae Seed, leaves Saptarangi S. oblonga Hippocrateaceae Root Makka Z. mays Poaceae Seed, stigma style, cob, leaf Aartagala/Coklebur X. strumarium Asteraceae Flower bulb, seed Sadampuspa/Sadabhar V. rosea Apocynaceae Whole Amlika/Tamarind T. indica Caesalpiniaceae Seed A. marmelos: Aegle marmelos, A. cepa: Allium cepa, A. sativum: Allium sativum, A. paniculata: Andrographis paniculata, A. indica: Azadirachta indica, C. bonducella: Caesalpinia bonducella, C. indica: Coccinia indica, C. longa: Curcuma longa, G. sylvestre: Gymnema sylvestre, T. indica: Tamarindus indica, V. rosea: Vinca rosea, X. strumarium: Xanthium strumarium, Z. mays: Zea mays, S. oblonga: Salacia oblonga, C. ramiflora: Cynometra ramiflora, J. curcas: Jatropha curcas, G. herbaceum: Gossypium herbaceum, E. golbulus: Eucalyptus globulus, B. purpurea: Bauhinia purpurea, W. somnifera: Withania somnifera, A. barbadensis: Aloe barbadensis, A. Arabica: Acacia Arabica, C. papaya: Carica papaya, P. ovata: Plantago ovata, S. anacardium: Semecarpus anacardium, I. batatas: Ipomea batatas, S. cumini: Syzygium cumini, M. charantia: Momordica charantia, M. paradisiacal: Musa paradisiacal, O. sanctum: Ocimum sanctum, P. amarus: Phyllanthus amarus, P. longifolia: Polyalthia longifolia, P. marsupium: Pterocarpus marsupium, T. foenum: Trigonella foenum, T. cordifolia: Tinospora cordifolia, A. augustum: Abroma augustum, A. pindrow: Abies pindrow, B. serrata: Boswellia serrata, B. variegata: Bauhinia variegata, E. officinalis: Emblica officinalis, E. alba: Eclipta alba, C. cajan: Cajanus cajan, F. religiosa: Ficus religiosa, C. sinensis: Camellia sinensis, H. auriculata: Hygrophila auriculata, G. glabra: Glycyrrhiza glabra, H. indicus: Hemidesmus indicus, J. communis: Juniperus communis, J. regia: Juglans regia, O. sativa: Oryza sativa, O. vulgare: Origanum vulgare, M. koenigii: Murraya koenigii, M. indica: Mangifera indica, N. sativa: Nigella sativa

• Type-2: It is non-insulin-dependent diabetes, in which MEDITIONAL PLANT USED AS body cells cannot use blood sugar efficiently for energy ANTIDIABETIC possibly due to insulin resistance, and especially, occur in older age. The term “medicinal plant” includes various types of plants used as medicines. The ancient Acharya believed that plants are only solutions to cure a number of health-related problems SYMPTOMS OF DIABETES MELLITUS and diseases. They conducted several studies about the same and experimented to arrive at exact conclusions about the Frequent urination, weight loss (Type 1), fatigue, excessive efficacy of different herbs that have medicinal value. The thirst, high blood level of glucose, nausea, vomiting, and ethnobotanical information reports suggested that near about blurred vision. 800 plants have antidiabetic potential.[3] Most of the medicines, thus prepared, are free of any side effects or reactions, and due to this reason, herbal medicines are growing in popularity AYURVEDIC VIEW ON DIABETES across the globe. The plants having medicinal properties MELLITUS (MADHUMEHA) provide rational means for the treatment of several diseases, which are otherwise considered difficult to cure. In Ayurvedic literature, diabetes mellitus is considered as Madhumeha. Acharya Charaka in Charaka Samhita Sutra Sthana seventeen beautifully described its pathogenesis, LIST OF AYURVEDIC MEDICINAL PLANTS excessive intake of heavy, oily, acidic and salty diet, WITH ANTIDIABETIC ACTIVITY AND intake of newly mature grains and excess of liquids, habits RELATED BENIFICIAL PROPERTY of sleeping on a comfort bed, free from any worry and exercise, devoid of any biopurification, and increase the 1. Momordica charantia: It contains Charantin, ascorbic amount of Kapah, Pitta, Meda, and Maans in the body, these acid, and momordicine chemicals. Fruit decoction of excess amount obstructed the flow of Vayu (air), and hence, karela taking in the morning empty stomach at least Vayu gets aggravated and this aggravated vayu takes oja 1 month it is helpful to bring back the blood glucose dhatu in the vasti (urinary bladder) region and produced level normal. Ethanolic extracts of M. charantia kricchasadhya (control with difficulty) and Madhumeha (200 mg/kg) showed a hypoglycemic effect on normal (diabetes mellitus).[2] and Streptozotocin induce diabetic rats.[4]

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2. Gymnema sylvastre: It contains gymnemic acid, Methanolic fruit extract contains glutamic acid, saponin, gymnestrogenin, and gymnemagenin chemicals. It tannin, steroids, and ellagic acid. C. indica decreases cures diabetes by decreases high glucose level in the blood glucose level in diabetic patient treated with dried blood and leads to proper functioning of insulin and extract for 6 weeks. It has restore lipoprotein lipase also minimizes or stops eating sweets in the diabetes enzyme activity, lactate dehydrogenase, and glucose 6 patients. According to the Sushruta it helps to care for phosphatase which was increased in diabetic patient.[10] Madhumeha, i.e., glycosuria.[5] 10. Curcuma longa: It contains curcumin, volatile oils, 3. Mangifera indica: It contains mangiferin, catechin, curcuminoids, zingiberene, sesquiterpenes, zingiberene, and protocatechin acid. The aqueous extract produces and resins. Aqueous extract dose of C. longa after 30 min decreases of blood sugar level in normoglycemic but no incubation shows hyperglycemic condition to inhibit any effect on streptozotocin diabetic-induced mice under release insulin and decreases oxidative stress in diabetic the same condition compared oral dose of chlorpropamide. animals.[11] Thus, M. indica shows hypoglycemic activity.[6] 11. Murraya koenigii: It contains quercetin, carbazole, and 4. Allium cepa: It contains flavonoids, flavonols, cycloalliin, murrayacine chemicals. It is very beneficial for Type 1 quercetin-3-glucoside, fructose, and mannose. The dried diabetic patient. Everyday chewing of 6–8 Murraya onion powder produces antihyperglycemic activity in koenigii leaves reduces glucose level in blood.[12] diabetic rabbits by various ether soluble fractions as 12. Pterocarpus marsupium: It contains pterostilbene and well as insoluble fractions. S-methyl cysteine sulfoxide pterocarpol. It helps renewal of the damaged beta cells. (SMCS) (200 mg/kg for 45 days) sulfur-containing The presence of tannates chemical in P. marsupium compound amino acid from A. cepa to alloxan-induced plant extract shows hypoglycemic activity. Studies diabetic rats controlled blood glucose. Single dose of have revealed that ethanol and aqueous extracts of PM onion juice (50 gm) taken orally decreases post-prandial heartwood, their subfractions, and (-)-epicatechin from glucose level in diabetic patients.[7] Pterocarpus marsupium bark increase insulin release. 5. Allium sativum: It contains sulfur-containing compounds Ethanol extract of PM heartwood given for 10 days that is Allicin, which is produced enzymatically from increased serum insulin concentration in Streptozotocin- Allin. It also contains 2.3% organosulfur compound, induced diabetic rats.[13] Flavonoids fraction P. marsupium 28% carbohydrate, 2% proteins, 2% free amino acid show pancreatic B-cell regeneration activity.[14] (mainly arginine), 65% water, 1.5% fiber, 0.15% 13. Ocimum sanctum: It contains volatile oil such as lipids, 0.07% saponins, and 0.08% phytic acid. In eugenol and caryophyllene, flavonoids, saponins, Allium sativum, a sulfur-containing compound Allicin and triterpenoids such as ursolic acid and rosmarinic showed to have important hypoglycemic activity due acid. The leaf aqueous extract of O. sanctum reported to improved hepatic metabolism, better insulin release decreases in blood glucose level in both normal and from pancreatic beta cells.[8] induced diabetic rats (by alloxan).[15,16] A mild changes 6. Aegle marmelos: It contains tannins, alkaloids (aegeline and or decreases in total cholesterol levels were also noted. aegelinin), active principle (marmelosin), and coumarin 14. Phyllanthus amarus: This plant is rich in chemical (marmesin). The leaf extract of A. marmelos shows components such as brevifolin, carboxylic acid, hypoglycemic activity in streptozocin-induced diabetes.[9] astragalin, methyl salicylate, alkaloids, cymene, lignans, 7. Acacia arabica: It contains mixture of calcium, potassium, ellagic acid, nirurin, niruretin, niruriside and phyllanthin and magnesium salts of Arabic acid. The gum also contains etc. Conventionally, P. amarus is used in diabetes peroxidase, pectinase and oxidase, and L-arabinose. The treatment. The methanolic plant extract also decreases plant extract of A. arabica acts as an antidiabetic agent the blood glucose level in alloxan diabetic rats.[17] by increasing the secretion of insulin. When administer 2, 15. Trigonella foenum graecum: It contains carbohydrates, 3, and 4 g/kg body weight, seed fine particles of Acacia fiber, proteins, and amino acid such as 4-hydroxyleucine. arabica to normal rabbit’s induce hypoglycemic effect by Chemicals isolate from Trigonella foenum graecum seed enhancing release of insulin from b cells.[10] fibers, proteins, and saponins given 21 days to alloxan 8. Azadirachta indica: Azadirachta indica also containing induce diabetic dog, and it shows antihyperglycemic nimbidinin, nimbin, nimbolide, nimbilic acid and activity with decrease high plasma glucagon. Trigonella nimbinin. Gedunin is a major source from neem’s foenum graecum seeds also increase glucose metabolism seed. It also contains tannin, gallic acid, margolonon and normalize creatinine kinase activity in skeletal and polysaccharide. It also contains azadirachtin, muscle, heart, and liver of diabetic rats.[18] mahmoodin. Hydroalcoholic extract of Azadirachta 16. Enicostemma littorale: It is a rich source of bitter principle indica showed anti-hyperglycemic effect and like swertimarine, ophelic acid, and alkaloids such as hypoglycemic effect in normal streptozocin induced gentianine and tannins. Methanolic extract of E. littorale diabetic rats because deposition of glycogen in the shows hypoglycemic activity and antioxidants property. isolated rat hemidiaphragm.[9] This extract increases insulin lavel and antioxidant 9. Coccinia indica: It contains flavonoids, resins, alkaloids, property also in diabetic induce rats.[19] fatty acids, asparagine, and proteins in high amount. 17. Andrographis paniculata: It contains bitter substance

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such as Kalmeghin and andrographolide and also CONCLUSION contains diterpene lactones. It decreases blood glucose level by the glucose tolerance test. Ahmad and Asmawi Diabetes is probably the world’s highest growing metabolic reported that the drug inhibits glucose absorption in the disease, herbal medicines are more and more becoming intestine.[20] trendy, and hence, it is careful to search for options from 18. Caesalpinia bonducella: It contains Caesalpinia F and medicinal plant extracts for new antidiabetic hypoglycemic bitter principle such as bonducin. Karanj aqueous extract substances. Plant products can be used as adjuvant or even was tasted in fasted, fed, glucose-loaded and streptozocin- may change the artificial drugs in the antidiabetic treatment, induced diabetic rat. This drug shows a positive effect in as they have no confirmed side effects. Therefore, there is streptozocin-induced diabetic rat, alloxan diabetic rat, a need of more well-documented clinical trials and more and glucose loaded. This drug is best oral hypoglycemic laboratory work to isolate the active principles in medicinal agents.[21] plants and their pharmacological actions and toxicity. 19. Musa paradisiaca: It is a rich source of vitamins, carbohydrates, minerals, and proteins such as albumin, gluteline, prolamine, and globulin. Amylose presents REFERENCES in unripe fruit. It also contains iron, calcium, sodium, gamma aminobutyric acid, magnesium, and phosphorus. 1. Watt J, Wood C, editors. Talking Health: Conventional Vitamins present in fruits are niacin, ascorbic acid, and Complementary Approaches. London: Proceedings folic acid, carotene, and inositol. The hypoglycemic of the Royal Society of Medicine; 1988. effect of green and mature fruits of M. paradisiaca 2. Charaka. Charaka Samhita. Sutra Sthana 17. Vol. 700BC. methanolic extract reduces blood glucose level normal Varanasi, India: Chaukhamba Publications; 1997. p. 215. [22] and chlorpropamide induce diabetic rats. 3. Alarcon-Aguilara FJ, Roman-Ramos R, Perez-Gutierrez S, 20. Polyalthia longifolia: It contains alkaloids, polyphenolic Aguilar-ContrerasA, Contreras-Weber CC, Flores-Saenz JL. compound, saponin, glycosides, tannins, and Study of the anti-hyperglycemic effect of plants used as diterpeniods. The chloroform extract of stem bark of antidiabetics. J Ethnopharmacol 1998;61:101-10. Kasthdaru was examined by alloxan induce diabetic rat 4. Ayyanar M, Sankarasivaraman K, Ignacimuthu S. and euglycemic rats after a single dose of 200 mg/kg p.o Traditional herbal medicines used for treatment of and prolonged treatment of 100 mg/kg p.o for 10 days. diabetes among two major tribal groups in South Tamil The results show antihyperglycemic activity (P<0.01). Nadu. Ethnobot Leaf 2008;12:276-80. Glibenclamide showed hypoglycemic activity in 5. Masttuda H, Morikawa T, Yoshikawa M. euglycaemic rats, but the said extract did not show Antidiabeticogenic constituents from several nature [23] hypoglycemic activity. medicine. Pure Appl Chem 2002;7:1301-8. 21. Tinospora cordifolia: It contains alkaloids, steroids, 6. Rajesham VV, Ravindernath A, Bikshapathi DV. A review diterpenoid lactones, phenolic, aliphatic compounds, on medicinal plant and herbal drug formulation used I sesquiterpenoid, and glycosides. Calcium and diabetes mellitus. Indo Am J Pharm Res 2012;2:1200-12. phosphorus are present major amount in leaf. Root 7. Das AV, Padayatti PS, Paulose CS. Effect of leaf extract extract of T. cordifolia orally administered for 6 weeks, of Aegle marmelose (L.) correa ex roxb. On histological it reduces blood and urine glucose level in lipids, serum, and ultrastructural changes in tissues of streptozotocin and tissue in alloxan-induced diabetic rats. Alcoholic induced diabetic rats. Indian J Exp Biol 1996;34:341-5. and aqueous extract of guduchi reduces blood glucose 8. Singh LW. Traditional medicinal plants of Manipur as level and increases glucose tolerance in rodents.[24] anti-diabetics. J Med Plant Res 2011;5:677-87. 9. Biswas K, Chattopadhyay I, Banerjee RK, Bandyopadhyay U. Biological activities and medicinal DISCUSSION properties of neem (Azadirachta indica). Curr Sci 2002;82:1336-45. In Ayurvedic literature, diabetes mellitus is considered as 10. Antia BS. Coccina indica plants with hypoglycemic Madhumeha, it is a type of Vataja Prameha and caused by activity. J Ethno Pharmacol 1989;26:1-55. aggravation of Vata either due to obstruction of channels 11. Chuengsamarn S, Rattanamongkolgul S, created by Kapha, Pitta, Meda, and Mansa or due to Dhatu Luechapudiporn R, Phisalaphong C, Jirawatnotai S. Kshaya. In Ayurveda, plants are a natural source of drugs; Curcumin extract for prevention of Type 2 diabetes. their medicinal value are studied by different scholars Diabetes Care 2012;35:2121-7. for antidiabetic activity, and most of the plants along with 12. Ganesan P, Phaiphan A, Murugan Y, Baharin BS. hypoglycemic activity also show antioxidant activity as Comparative study of bioactive compounds in curry required in diabetic patient (Table 1). Traditional medicinal and coriander leaves: An update. J Chem Pharm Res plants having bitter and astringent taste shows hypoglycemic 2013;5:590-4. activity due to their Kapha and Pitta pacifying action medo 13. Mishra A, Srivastava R, Srivastava SP, Gautam S, shoshak properties. Tamrakar AK, Maurya R, et al. Antidiabetic activity

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of heart wood of Pterocarpus marsupium Roxb. 19. Vasy MJ, Gupta VT. Dose dependent hypoglycemic and analysis of phytoconstituents. Indian J Exp Biol effect of aqueous extract induced diabetic rats. Phytomed 2013;51:363-74. Int J Phytother Phytopharm 2003;10:196-9. 14. Jahromi MA, Ray AB, Chansouria JP. Antihyperlipidemic 20. Ghos D, Uma R, Thejomoothy P, Velluchamy GJ. “Res effect flavonoids from Pterocarpus marsupium. J Nat in Ayur.Sid.” 1990;11:1-4. Prod 1993;56:898-994. 21. Biswas and Coworkers. To study Caesaplinia bonducella 15. Ria V, Iyer U, Mani UV. Effect of tulsi (Ocimum methanol alloxan induced diabetic rats. Pharm Biol sanctum) leaf powder supplementation on blood sugar 1997;41:388-91. levels, serum lipids and tissues lipids in diabetic rats. 22. Mallick C, Maiti R, Ghosh D. Comparative study Plant Foods Hum Nutr 1997;50:9-16. on antihyperglycemic and antihyperlipidemic 16. Vats V, Grover JK, Rathi SS. Evaluation of effects of separate and composite extract of seed of antihyperglycemic and hypoglycemic effect of Trigonella Eugenia jambolana and root of Musa paradisiaca in foenum-graecum Linn, Ocimum sanctum Linn and streptozotocin-induced diabetic male albino rat. Iran J Pterocarpus marsupium Linn in normal and alloxanized Pharmacol Ther 2006;5:27-33. diabetic rats. J Ethnopharmacol 2002;79:95-100. 23. Dusul A, Geaser T. The antidiabetic activity of the bark of 17. Raphael KR, Sabu MC, Kuttan R. Hypoglycemic effect Polyalthia Longifolia. J Agric Food Chem 1990;17:704. of methanol extract of Phyllanthus amarus Schum and 24. Gupta SS, Verma SC, Garg VP, Rai M. Antidiabetic Thonn onalloxan induced diabetes mellitus in rats and effect of Tinospora cordifolia. I: Effect on fasting blood its relation with antioxidant potential. Indian J Exp Biol sugar level, glucose tolerance and adrenaline induced 2002;40:905-9. hyperglycemia. Indian J Med Res 1967;55:733-45. 18. Manisha M, Priyanjali D, Jayant L, Saroj G, Thomas PA. Indian herbs and herbal drugs used for the treatment of diabetes. J Clin Biochem Nutr 2007;40:163-73. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S22 Ethnopharmacology and pharmacology of Kigelia africana (Lam.) Benth.

Anupriya Singh, Snehal Kumari, Ambrish Kumar Singh, Narendra Kumar Singh Pharmacy Ayurveda Research Laboratory, Rajiv Gandhi South Campus, Banaras Hindu University, Mirzapur, Uttar Pradesh, India

Abstract

African plant Kigelia africana (Lam.) Benth. belonging to the family Bignoniaceae is widely distributed in the South, Central, and West Africa. Tree of K. africana is approximately 20 m long, either evergreen or deciduous depending on the rainfall condition in different part of the world. Due to its huge sausage or cucumber-like

REVIEW ARTICLE REVIEW fruit, K. africana is commonly referred to as sausage or cucumber tree. Different parts of K. africana have been used for various medicinal purposes in different parts of the world. In India, K. africana is well known as Balmkheera. A very famous slogan is used in different parts of Uttar Pradesh (India) for K. africana as “Balamkheera jo bana de pet ko heera.” Different parts of this plant used by ethnic groups throughout the world for the treatment of common skin diseases such as fungal infections, psoriasis, eczema, boils, leprosy, syphilis, skin cancer gynecological complaints, constipation, tapeworm infection, jaundice, ulcers, sores, pneumonia, malaria, diabetes, and waist pain. Pharmacological activities of different extracts as well as isolated compounds of the plant are reported as analgesic, antipyretic, anti-inflammatory, hepatoprotective, antidiabetic, antibacterial, antifungal, nematocidal, antiamebic, antiviral, antitrypanosomal, antiamebic, antimalarial, antidiarrheal, anticancer, antioxidant, aphrodisiac, and wound healing activity have been studied using different methods. In the present article, data have been collected on the ethnopharmacology and pharmacology of K. africana up to June 2017.

Key words: Balamkheera, Kigelia africana, Muratina, sausage tre

INTRODUCTION K. africana are about 30–50 cm long, pinnate, and leaflets are up to 20 cm long and 6 cm broad.[7] The wood of plant is igelia africana, belongs to the family pale brown or yellowish in color.[8] Flowers of K. africana Bignoniaceae, is native from Africa.[1] are bell-shaped, orange-to-red or purplish green with up to It is widely distributed in the South, 10 cm width. It hangs down from branches on long flexible K stems and bloom at the night.[9] Flower of K. africana Central, and West Africa. Plant of K. africana is a moisture-loving tree mostly found on river has five-lobed calyx and corolla. Corolla is yellowish on [10] banks, along streams, in floodplains of Nigeria, outside and purplish on inside. The fruit of K. africana is Cameroon, Kenya, Guinea, Senegal, and open incredibly large, and it can grow up to 1 m × 18 cm with a [11] woodland from KwaZulu-Natal (South Africa) weight up to 12 kg. The fruit of K. africana is indehiscent to Tanzania, Chad, and Namibia.[2] In India, with a woody wall and heavily marked with lenticels at the K. africana is well known as Balmkheera. pod surface. The fruit of K. africana is gray-brown in color [5] A very famous slogan is used in different and contains many seeds when matured. The fruit of the parts of Uttar Pradesh (India) for K. africana plant is fibrous and unripe fruit being poisonous when taken [12] [3] internally. Although the unripe fruits of K. africana are as “Balamkheera jo bana de pet ko heera.” [10] Due to its huge sausage or cucumber-like fruit, toxic yet it is used externally as a medicine in Africa. K. africana is commonly referred to sausage or cucumber tree.[4] Tree of K. africana is Address for correspondence: approximately 20 m long, either evergreen or Dr. Narendra Kumar Singh, Ayurvedic Pharmacy deciduous depending on the rainfall condition Research Laboratory, Rajiv Gandhi South Campus, Banaras Hindu University, Barkachha, in different parts of the world.[5] The bark of Mirzapur – 231 001, Uttar Pradesh, India. K. africana is gray and smooth at young while Mobile: +91‑8869939142. peeling occurs on older tree. It can be 6 mm E-mail: [email protected] thick on a 15 cm branch.[6] The leaves of

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S23 Singh, et al.: Pharmacology of Kigelia africana

ETHNOPHARMACOLOGY Searsia nebulosa are mixed together and three handfuls are boiled in 2 L of water for 30 min and cooled before straining, Different parts of K. africana have been used for various and half a cup of this decoction is taken twice a day.[21] In medicinal purposes in different parts of the world.[2] The Namibia and South Africa, stem and leaves of K. africana tree is most widely used in the treatment of various common are crushed together, boiled in water till concentrate, and skin diseases such as fungal infections, psoriasis, eczema, used to wash or rub onto the infected skin parts for the boils, leprosy, syphilis, and skin cancer.[13] Root decoction of treatment of eczema and herpes.[30] Fruits and stem bark of K africana is drunk to treat gastrointestinal problems.[14] In K. africana ground and boiled in water and taken orally for Nigeria, decoction of the roots of K. africana is used in ante- the treatment of stomach ailments usually worms infection and post-natal disorders, fibroid, and conception.[15] In South in children.[31] In South Africa, a handful of leaves and roots Africa and Ethiopia, hot macerate of the roots of K. africana of K. africana, chopped Hypoxis hemerocallidea corm, and is taken orally in gynecological complaints, constipation, crushed Senecio serratuloides are boiled in 5 L of water and and tapeworm infection.[16] The root bark of K. africana half a cup taken thrice a day for the treatment of sexually is also recommended for the treatment of uterus cancer.[17] transmitted infections and sores.[32] K. africana fruits, stem Root barks of K. africana are also useful in the treatment bark, and roots are boiled and used medicinally to cure of venereal diseases, hemorrhoids, and rheumatism.[18] Stem post-parturition hemorrhage.[33] K. africana is also used for bark of K. africana is useful in the treatment of rheumatism, internal applications including the treatment of dysentery, dysentery, venereal diseases, gynecological conditions, worm infestations, pneumonia, toothache, malaria, diabetes, hemorrhages, epilepsy, wounds, sores, abscesses, diarrhea, venereal diseases, convulsions, and antidote for snakebite. [2,23,34] and edema.[19] In Cameroon, decoction of stem bark was In South Africa, roasted seeds of K. africana are eaten taken orally as abortifacient, in the treatment of filariasis and for the treatment of pneumonia, malaria, diabetes, and waist cataract.[20] In Tanzania and Nigeria, hot decoction of stem pain and applied on the affected area of the body to cure [3,35] bark was taken orally after parturition as galactagogue.[21] In fungal infection and eczema. In Kenya, the roasted seeds South Africa and Cameroon, decoctions of powdered stem of K. africana are mixed with beer and taken orally for the [36] bark were mixed in porridge and taken orally for the treatment enlargement of sexual organs. of infertility.[21,22] The decoction of the stem bark of plant is drunk for relief from headaches and treatment of epilepsy.[14] Infusion of stem bark of K. africana was taken orally in the PHARMACOLOGICAL ACTIVITIES OF treatment of hyperpyrexia and gonorrhea in Tanzania.[23] In K. AFRICANA Benin, Ivory Coast, and South Africa, decoction of the leaves of the plant is drunk for the treatment of jaundice.[24] Ash Analgesic Activity of K. africana leaves is mixed with honey and used for the treatment of high blood pressure.[14] In Central Africa, unripe Methanol extract of the stem bark of K. africana (100, 200, fruit of K. africana is used for the dressing of wounds, for the and 500 mg/kg body weight orally) was evaluated using treatment of rheumatism and hemorrhage.[25] In Botswana, hot plate test and mouse writhing assay in mice for the K. africana fruits are boiled with milk, cooled, and taken evaluation of analgesic activity. A significant dose-dependent orally as sexually transmitted diseases remedy.[26] In decrease in writhing was recorded in the extract-treated Tanzania, K. africana fruits are boiled and taken orally for the (500 mg/kg body wt. p.o.) and aspirin-treated (100 mg/kg body treatment of anemia, especially for pregnant women.[23] The wt. i.p.) mice (29.6 ± 7.31 and 36.8 ± 5.8/30 min, respectively) paste of K. africana fruits is used for leprosy in Kurukshetra as compared to the control mice (85.0 ± 1.34/30 min). district in Haryana (India). In Africa and India, the paste of Intraperitoneal injection of acetic acid (0.6% in normal powdered K. africana fruits is rubbed around the infected saline, at a dose of 10 mL/kg body weight) was administered area of skin for the treatment of skin cancer and to reduce 60 and 30 min, respectively, before the administration of the breast metastasis.[27] In Central Africa, K. africana fruits test and standard drugs. In the mouse writhing assay, extract are used to treat rheumatism.[16] Tonga women of Zambezi caused statistically significant (P < 0.0001) inhibition of the valley regularly apply cosmetic preparation of K. africana number of writhes. Extracts at the dose of 200 and 500 mg/ fruits on their faces to ensure a blemish-free complexion. kg produced a higher inhibition as compared to standard drug [28] Unripe K. africana fruits are used as vermifuge.[29] Beer aspirin (100 mg/kg). The inhibitory effect was 139 and 124% (Muratina) prepared from the extract of K. africana fruits of the effect produced by aspirin at 200 and 500 mg/kg doses, is used during children bath for the treatment of measles. respectively. The extract failed to increase mice reaction time Either fresh or crushed dried fruits of K. africana are used on hot plate. The difference between the mean reaction time for the treatment of ulcers, sores, and syphilis.[3] In South of the K. africana-treated groups and the control group was Africa, chopped stem bark and fruits of K. africana are boiled not statistically significant at all doses tested. Its effect was in 2 L of water for 1 h, cooled before straining, and taken not comparable to morphine which had a mean reaction orally half a cup thrice a day for blood cleansing and pelvic time of more than 2 min which was the cutoff point (P < pains during pregnancy. For the treatment of dysmenorrhea, 0.0001).[37] Inhibition of acetic acid-induced writhing in equal amounts of dried or fresh stem bark of K. africana and mice suggests that the analgesic effect of the extracts may be

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S24 Singh, et al.: Pharmacology of Kigelia africana peripherally mediated through the inhibition of the synthesis extract of stem bark at the dosage of 100, 200, and 500 mg/ and release of prostaglandins.[38] Analgesic activity of the kg body weight has been reported to have anti-inflammatory roots of K. africana was found less effective as compared activity against carrageenan-induced paw edema in guinea to its stem, leaves and fruits.[16,39] The methanol extract of pigs. Indomethacin was used as a reference drug. It was flowers of K. africana decreased the number of acetic acid- found that extract showed anti-inflammatory effect in a dose- induced writhing in mice treated orally at the dose of 100, dependent manner with maximum activity at the dose of 200, and 400 mg/kg as compared to control animals. The 500 mg/kg body weight dose. Reduction in the paw volume analgesic activity of the extract was found in dose-dependent in animals treated with the extract (500 mg/Kg) was found manner with inhibition of writhing of 48.72%, 53.42%, and comparable with the standard drug indomethacin (10 mg/Kg), 80.77%, respectively, for the designated doses of the extract, the percentage inhibition produced by the extract was 98% at whereas the standard drug (diclofenac sodium 20 mg/kg) the 2nd h, 94.8% at the3rd h, and 85% at the 5th h.[37] showed writhing inhibition of 76.50%. Reaction time was prolonged significantly and dose dependently in hot plate Compounds, verminoside, and verbascoside isolated from the test at different time intervals. The extract also decreased the methanol extract of fruits showed anti-inflammatory activity. number of licking times of the hind paw in both the first and It was found that verminoside inhibits the nitric oxide synthase second phases in formalin-induced nociception in mice.[39] (iNOS) and NO release from macrophages as stimulated by bacterial lipopolysaccharides,[1] while verbascoside inhibits Analgesic activity of ethanol extract of the leaves of nuclear factor-ĸβ activation, tumor necrosis factor-α release, K. africana was carried out using hot plate method on albino iNOS activity, and nuclear translocation.[43,44] rats. Paracetamol (150 mg/kg) was used as standard drug. The extract at the dose of 100, 200, and 400 mg/kg showed Hepatoprotective Activity statistically significant elongation in hot plate reaction time (P < 0.0001) as compared with the standard drug paracetamol Aqueous leaves extract of K. africana showed significant (150 mg/kg). The extract at the dose of 400 mg/kg was found hepatoprotective activity in paracetamol-induced liver more effective than the standard drug paracetamol.[40] damage in rats.[45]

Antipyretic Activity Methanol extract of the fruits of K. africana was assessed for its effect in CCL4-induced liver toxicity in male Wistar rats. The methanol extract of stem bark of K. africana showed Silymarin (50 mg/kg) was used as a standard drug. K. africana antipyretic activity on turpentine-induced pyrexia in fruits extract are found to be toxic (but not fatal) to Wistar rats male Wistar rats. Administration of extract (50, 100, and when given at the dose of 100, 200, and 400 mg/kg orally. 150 mg/kg body weight) showed decreasement in the level K. africana fruit extracts change the growth rates, cytoplasmic of elevated rectal temperature in dose-dependent manner. fatty vacuolation, and necrosis of the centrilobular hepatocytes Aspirin (100 mg/kg body weight) was used as reference drug. in the liver attributed to the increases in the activity of enzyme The maximum antipyretic activity of extracts was occurred in aspartate aminotransferase and lower concentration of albumin the 4th h (50 mg/kg, 100 mg/kg, and 150 mg/kg body weight and decreased activity of alanine transaminase.[46] K. africana as well as the aspirin reduced elevated rectal temperature by fruit extract (100 mg/kg) showed protective effects for liver 1.41%, 2.09%, 3.07%, and 2.40%, respectively), indicating disease due to its ability to act as an antioxidant.[45] slow but steady passive diffusion of the bioactive compounds across the cell membrane. The antipyretic activity of the Antidiabetic Activity extract at the dosages of 50 mg/kg and 100 mg/kg body weight showed no statistically significant difference (P > 0.005) as Methanol extract of the leaves of K. africana compared with the control group. However, the group treated (100–400 mg/kg) was evaluated for its antidiabetic activity with extract at the dosage of 150 mg/kg body weight was in alloxan (120 mg/kg)-induced diabetic rats where comparable to the group of rats treated with standard drug glibenclamide (5 mg/kg) was used as a standard drug. aspirin (P > 0.05).[41] Methanol extract of the plant at the dose of 200–400 mg/kg Anti-inflammatory Activity decreases the level of blood glucose significantly while extract at the dose of 100 mg/kg failed to do so. Treatment of diabetic Anti-inflammatory activity of methanol extract from rats with methanol extract (200–400 mg/kg) of the plant the leaves of K. africana was evaluated in carrageenan- produced a significant reduction in serum levels of triglyceride induced paw edema in rats. Methanol extract showed a and cholesterol in a dose-dependent manner which was found significant anti-inflammatory activity at the dose level of comparable to standard drug glibenclamide.[47] 150 mg/kg as compared to the standard drug diclofenac sodium (15 mg/kg body weight) by reducing the hind paw Daily administration of the defatted methanol extract (for diameter by 0.21% and 1.10%, respectively.[42] The ethanol 21 days) of flower of K. africana in streptozotocin-induced

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S25 Singh, et al.: Pharmacology of Kigelia africana diabetic rat causes statistically significant (P < 0.001) zone of inhibition 7.0 ± 0.0 mm at the concentration of reduction in the level of blood glucose in a dose-dependent 1.80 mg/mL. Kojic acid gives zone of inhibition for all manner from 288.45 ± 2.30 mg/dL to 152.48 ± 2.7 mg/dL and bacterial strain E. coli (6.0 ± 0.0 mm), P. aeruginosa (8.0 ± 298.29 ± 3.50 mg/dL to 138.43 ± 3.5 mg/dL at the doses of 0.0 mm), S. typhi (6.0 ± 0.0 mm), and S. aureus (11.0 ± 0.0) 250 and 500 mg/kg, respectively. Glibenclamide (10 mg/kg) at the concentration of 1.744 mg/mL. Minimum inhibitory was used as a standard drug. Total blood cholesterol and concentration (MIC) value of p-coumaric acid was found triglycerides were reduced while the level of high-density >0.83 ± 0.0 mg/mLfor E. coli, P. aeruginosa, and S. aureus, lipoprotein cholesterol level was significantly improved as whereas 0.41 ± 000 mg/mL for S. typhi.[51] compared to diabetic control group (vehicle group).[48] Fruit extract of the plant showed antidiabetic activity (reduces sugar The aqueous, methanol, and chloroform extracts of K. africana level in the blood) due to the presence of the terpenoids.[49] bark were tested for antibacterial activity against E. coli, Enterobacter aerogens, Klebsiella pneumoniae, S. typhi, Proteus vulgaris, P. aeruginosa (Gram-negatives), S. aureus, Antibacterial Activity and Bacillus cereus (Gram-positives) using disc diffusion method. Streptomycin (10 mg/disc) was used as standard Antibacterial screening of different stem bark extracts drug. The ethanol and aqueous extracts of K. africana bark as well as isolated compound was carried out using disk showed antibacterial activity with zone of inhibition 20 mm diffusion method using amoxicillin (2 mg/discs) as positive and 17 mm.[52] It has been found that organic extracts showed control. Negative control was prepared using 10% dimethyl greater activity as compared to aqueous extract.[53] sulfoxide as a solvent. The methanol extract of stem bark was suspended in water and successively extracted with Ethanol extract of the fruit of K. africana presented a higher n-hexane-EtOAc, EtOAc, and water. One Gram-positive activity than the aqueous extract with zone of inhibition bacteria, Staphylococcus aureus CIP 7625, and three Gram- 17 mm and 20 mm, respectively. Kirby–Bauer disc diffusion negative bacteria, Pseudomonas aeruginosa CIP 76110, method was used for the evaluation of antibacterial study. The Salmonella typhi, and Escherichia coli ATCC 25922, are highest activity was exhibited against S. typhi and P. vulgaris, used as test microorganisms. Zone of inhibition (mm) of whereas moderate activity was found against E. coli, methanol extract of stem barks was found to be 6.0 ± 0.0, 6.0 S. aureus, and B. cereus. Less activity was observed against ± 0.0, 0.0 ± 0.0, and 0.0 ± 0.0 for E. coli, P. aeruginosa, S. the remaining strains, namely, E. aerogens, K. pneumoniae, typhi, and S. aureus, respectively. Zone of inhibition (mm) of and P. aeruginosa.[54] n-hexane-EtOAc fraction for E. coli, P. aeruginosa, S. typhi, and S. aureus was found to be 6.0 ± 0.0, 6.0 ± 0.0, 0.0 ± 0.0, Methanol extracts of the fruits and roots of K. africana and 7.0 ± 0.0, respectively. EtOAc fraction showed that zone showed a significant inhibitory effect against Gram- of inhibition for E. coli, P. aeruginosa, S. typhi, and S. aureus positive bacteria tested but found nonsignificant against was found to be 0.0 ± 0.0, 0.0 ± 0.0, 0.0 ± 0.0, and 6.0 ± the Gram-negative bacteria. Streptomycin sulfate was 0.0, respectively. Zone of inhibition of aqueous fraction of used as the standard antibacterial agent and showed zone stem bark was found to be 6.0 ± 0.0, 7.0 ± 0.0, 6.0 ± 0.0, and of inhibition 18–26 mm at the concentration of 1 mg/ 8.0 ± 0.0 for E. coli, P. aeruginosa, S. typhi, and S. aureus, mL against the Gram-positive organisms. It was observed respectively, while the zone of inhibition of standard drug that isolated compounds from the root of K. africana, amoxicillin for E. coli, P. aeruginosa, S. typhi, and S. aureus sesamin, 3-(2-hydroxy-ethyl)-5-(2‑hydroxypropyl) dihydro- was found to be 0.0 ± 0.0, 6.0 ± 0.0, 0.0 ± 0.0, and 0.0 ±0.0, furan-2 (3H)-one, 2-acethylnaphtho (2,3-b) furan-4,9- respectively.[50] quinone, 2-(1-hydroxyethyl)-naphtho (2,3‑b) furan-4,9- dione, 4-hydroxycinnamic acid, and ferulic acid were [55] Isolated compound 2-acetylfuro-1, 4-naphthoquinone responsible for antibacterial and antifungal activity. showed the zone of inhibition 6.0 ± 0.0 mm for P. aeruginosa Alkaloids showed promising activity against the bacteria [56] and S. aureus. Zone of inhibition of p-coumaric acid was Helicobacter pylori. found to be 6.0 ± 0.0 mm for E. coli, P. aeruginosa, and S. aureus while 7.0 ± 0.0 mm for S. typhi at the concentration Antifungal Activity of 0.452 mg/mL. Caffeic acid showed sensitivity only against E. coli with a zone of inhibition 6.0 ± 0.0 mm. Isolated Antifungal activity of methanol extracts of leaves and stem compound 2-(4-hydroxyphenyl) ethyl ester showed zone bark of K. africana was performed against Candida albicans of inhibition 6.0 ± 0.0 mm for E. coli and P. aeruginosa. using disk diffusion method. Chloramphenicol (1 mg/mL) Kigelinol showed antibacterial activity against E. coli and and clotrimazole (1 mg/mL) were used as standard drugs. S. aureus with zone of inhibition 6.0 ± 0.0 mm and 8.0 ± Zones of inhibition of methanol extract of leaves at the dose 0.0 mm, respectively. β-friedelinol showed the zone of of 10 mg/mL, 20 mg/mL, and 50 mg/mL were found to be inhibition against P. aeruginosa (6.0 ± 0.0 mm) and S. 15.50 ± 0.50, 18.50 ± 0.55, and 23.35 ± 0.45 mm, respectively. aureus (6.0 ± 0.0 mm) at the concentration of 1.7575 mg/mL. Methanol extract of K. africana stem bark showed zone of Pomolic acid was found active only for P. aeruginosa with inhibition 12.55 ± 0.55 mm, 15.50 ± 0.50 mm, and 18.5 ±

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S26 Singh, et al.: Pharmacology of Kigelia africana

0.25 mm at the concentration of 10 mg/mL, 20 mg/mL, of specioside was found comparable with metronidazole.[63] and 50 mg/mL, respectively. Zone of inhibition of standard Minecoside and verminiside isolated from the butanol extract drug clotrimazole was found 25.50 ± 0.50 mm. MIC value of stem bark of K. africana also possess antiamebic activity.[64] of leaves extract against C. albicans was found 2.5 mg/mL while clotrimazole showed MIC value 0.025 mg/mL.[57] The Antiviral Activity chloroform extract of K. africana stem bark showed the highest antifungal activity (MIC value 0.625–1.25 mg/mL) Antiviral activity of leaves extract of plant was performed as compared to the petroleum ether and methanol extract of against HIV-1 reverse transcriptase. Extract of the plant K. africana stem bark against the fungal strains Cryptococcus showed a weak inhibitory effect (11.13% and 33.07% neoformans, Candida tropicalis, Trychophyton rubrum, inhibition at the dose of 50 µg/mL and 100 µg/mL, Microsporum furfure, and Epidermophyton floccosum.[58] respectively). Methanol extract of fruits of the plant showed Aqueous, methanol, and ethyl acetate extracts of the fruits of 13.20% inhibition of reverse transcriptase at the dose this plant exhibited a broad spectrum of antifungal activity. 100 µg/mL while found inactive at the dose of 50 µg/mL. Antifungal activity was performed by modified disc diffusion Methanol extract of the fruits was tested against various viral method using ampicillin (2 µg) and nystatin (100 µg) as strains showed a weak activity against vesicular stomatitis standard drugs. Fungi Aspergillus niger, C. albicans, and virus while no any effect against herpes simplex virus Type 1, [65] Penicillium chrysogenum used as test microorganism. Coxsackie B2, and Semliki forest virus A7. Methanol, water, and ethyl acetate extracts inhibited the growth of fungi tested (75%). Only P. crysogenum was found Antitrypanosomal Activity resistant to all these extracts. Methanol extract showed the strongest inhibition to the growth of fungi A. niger, C. albicans, In vitro antitrypanosomal activity was performed for and P. chrysogenum with the MIC value of 1238, 841.2, and the compounds (isopinnatal, kigelinol, isokigelinol, and 989.7 µg/mL, respectively. MIC value of aqueous extract for 2-(1-hydroxyethyl)-naphtho-(2,3-b)-furan-4,9-quinone) fungi A. niger, C. albicans, and P. chrysogenum was found isolated from the dichlomethane extracts of stem and root, to be are 2487, 2060, and 2768 µg/mL, respectively, while exhibited antitrypanosomal activity against Trypanosoma MIC value of ethyl acetate was 1463, 1278, and 1744 µg/ brucei. Pentamidine was used as standard drugs.[66] mL for the fungi A. niger, C. albicans, and P. chrysogenum, respectively.[59] The methanol extract of the fruit of K. africana was found to be active against C. neoformans with Antimalarial Activity minimum fungicidal concentration >1 g/mL.[60] In vitro antiplasmodial activity of hexane and ethyl acetate fraction of methylene chloride/methanol (1:1) extract of Nematicidal Activity stem bark and isolated compounds was performed using W-2 (MRA-157), CAM10, and SHF4 strains. Ethyl acetate fraction Isovitexin, isolated from K. africana, was studied against showed a significant plasmodial growth inhibitory activity the Meloidogyne incognita (a cotton root-knot nematode) (IC50 value 11.15 µg/mL, 4.74 µg/mL, and 3.91 µg/mL for and it also produced a significant nematocidal mortality rate W-2, CAM10, and SHF4 strains, respectively), whereas (39.76%) compared against the control (2.18%), M. incognita n-hexane fraction showed a weak activity against W-2 (IC50 eggs extracted from Solanum melongena L. roots used as test value 73.78 µg/mL) and SHF4 (IC value 21.85 µg/mL). organism oxamyl served as control. Tolaside isolated from the 50 plant found more active than the standard compound oxamyl Specicoside isolated from ethyl acetate fraction showed at 30 min of exposure to the M. incognita with a percentage highest activity against W-2 (IC50 value 1.54 µg/mL) mortality of 29.43%, whereas standard drug oxamyl showed followed by 2β,3β,19α-trihy-droxy-urs-12-en-28-oic acid and 20.22% mortality. The crude methanolic extract of K. africana atranorin isolated from n-hexane fraction with IC50 value showed only a few hatches. The lowest concentration (25%) 1.60 µg/mL and 4.41 µg/mL, respectively. p-Hydroxycinnamic allowed some hatching, while the higher doses (50 and 75%) acid isolated from ethyl acetate fraction showed the least completely inhibited the hatching of eggs.[61,62] activity against W-2 strain with IC50 value 53.84 µg/mL. Chloroquine phosphate and ethyl acetate fraction showed

Antiamebic Activity antiplasmodial activity against CAM10 strain with IC50 value

0.13 ± 0.02 and 4.74 ± 1.18 µg/mL while the IC50 value of Butanol extract of the stem bark of K. africana exhibited chloroquine phosphate, n-hexane, and ethyl acetate fraction antiamebic activity (in vitro) against HK-9 strain of against SHF4 was found to be 0.10 ± 0.01, 21.85 ± 0.12, and Entamoeba histolytica by microdilution method using 3.91 ± 0.98 µg/mL, respectively. metronidazole as standard drug. Verminoside isolated from stem bark of K. africana have 2-fold antiamebic activities Isolated compounds atranorin, 2β,3β,19α-trihy-droxy- than standard drug metronidazole while antiamebic activity urs-12-en-28-oic acid, specicoside, p-hydroxycinnamic

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S27 Singh, et al.: Pharmacology of Kigelia africana acid, and chloroquine phosphate (standard drug) showed human embryonic kidney (HEK-293) cells. The seed oil antiplasmodium activity against CAM 10 strain with of K. africana suppressed cell growth of both HEK-293 [75] IC50 value 2.81 ± 1.07, 2.17 ± 0.55, 2.34 ± 1.15, 7.13 ± and Caco-2 in a dose-dependent manner. Verminoside 3.35, and 0.25 ± 0.04 µg/mL, respectively.[67] Kigelinol, (an iridoid derivative) and verbascoside (a phenylethanoid isokigelinol, isopinnatal, and 2-(1-hydroxyethyl) naphtha compound) were reported for their genotoxic tendencies.[76] (2, 3-b) furan-4,9-dione isolated from the roots of plants showed effective antimalarial activity. Lapachol isolated from the roots and wood of plant shows antimalarial ACTIVITY ON CENTRAL NERVOUS activity. Another compound, 2-(1-hydroxyethyl)naphtho SYSTEM (CNS) [2,3-b]furan‑4,9‑quinone obtained from the root bark of K. africana also shows an antimalarial activity against drug- Ethanol extract of stem bark of K. africana exhibited CNS [68] resistant strains of Plasmodium falciparum. Antimalarial stimulant activity at the dose of 400 mg/kg body weight in activity of pinnatal was investigated against P. falciparum, barbiturate-induced sleeping time and the rotarod bar test. and ECV-304 cell line displayed high inhibitory activity The difference in sleeping time was found significant in with IC value 2.2 ± 0.3 µg/mL.[69] Both the aqueous and 50 dose-dependent manner. The effect of extract of stem bark organic extract of K. africana leaves show antimalarial was also compared with standard drug caffeine and observed activity against P. falciparum parasite strains, K39 and that extract of stem bark produces shorter duration of sleeping V1/S with an IC50 value 53.2 ± 9.8 and 42.2 ± 12.2 µg/mL, [70] time as compared to caffeine (P < 0.05) indicating better respectively. stimulant properties. The extract of stem bark of plant had no any sedative effect as the animals maintained their balance Antidiarrheal Activity during entire period of the experiment in rotarod test.[77]

Antidiarrheal activity of methanol roots extract of K. africana was performed in castor oil-induced diarrhea in APHRODISIAC EFFECT rats using loperamide (4 mg/kg) as standard drug. Methanol extract of the roots of plant demonstrated a dose-dependent Aqueous extract of fruits reported to have fertility enhancing antidiarrheal effect which was accessed by measuring the effect in rats. It improves the sperm quality of African catfish incidence of feces, prevention of loose feces, production, and (Clarias gariepinus) and enhanced weight of testes.[78] delaying the onset of diarrhea. Methanol extract of roots at In vitro studies using extracts of the K. africana fruits in the dose of 500 and 1000 mg/kg body weight significantly adult male Sprague - Dawley rats for 28 days significantly reduced the frequency of diarrheal feces and the spontaneous increased (P < 0.001) the sperm count of rats and sperm propulsive movement of isolated jejunum (in vitro). Extract motility above 70%.[79] Stem bark of K. africana also shows at the dose of 500 mg/kg prolonged of the onset of diarrhea strong aphrodisiac properties.[78] Saponin present in the plant (P > 0.05), reduced the frequency of stooling and inhibited enhances the aphrodisiac properties due to their stimulatory loose stool production. At a higher dose (1000 mg/kg), it effect on androgen production.[80] produced greater effects, revealing that the extract produces dose-dependent antidiarrhea activity.[71] Aqueous extract of [72] roots of K. africana also possesses antidiarrheal activity. WOUND-HEALING ACTIVITY

Anticancer Activity Leaves of K. africana showed more potent activity in excision wound model and showed statistically significant influences th th Aqueous, ethanol, and dichloromethane extracts of the stem (P < 0.05) on wound closure from 7 to 15 day after bark and fruits of K. africana were studied for anticancer treatment while the methanol extract of stem bark exhibited activity against four melanoma cell lines and a renal cell similar effects on wound healing but from 10th to 18th day carcinoma line (Caki-2) using (3-(4,5-dimethylthiazol- after treatment. Verbascoside isolated from the plant showed 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and wound healing as well as antinociceptive properties.[81] sulforhodamine B assays. Lapachol isolated from these Aqueous extract of stem bark showed wound-healing activity extracts found effective in the treatment of solar keratosis and at the dose of 250 and 500 mg/kg.[82] Kaposi sarcoma (an HIV-related skin ailment).[73] Lapachol shows cytotoxicity against Artemia salina in the brine shrimp bioassay, indicating antitumor potential.[74] It was reported ANTIOXIDANT PROPERTIES that the phytoconstituents norviburtinal and isopinnatal found active against melanoma cell lines.[34] In vitro antioxidant activity of different extract of the roots of K. africana was measured by 1,1-diphenyl-2-picrylhydrazyl Seed oil of K. africana showed a significant antiproliferative assay using α-tocopherol as standard antioxidant.[83] Ethyl effect against human colon adenocarcinoma (Caco-2) and acetate extract of K. africana roots showed a higher antioxidant

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S28 Singh, et al.: Pharmacology of Kigelia africana value and total antioxidant activity peaked at 0.25 mg/mL from South India. Int J Appl Pharm 2010;2:20-2. and declined at higher concentration. Hexane extract of the 8. Aliyu AB, Musa AM, Abdullahi MS, Oyewale AO, roots of K. africana showed an increase in total antioxidant Gwarzo US. Activity of plant extracts used in Northern activity as concentration increases in dose-dependent manner. Nigerian traditional Mmdicine against methicillin- Methanol root extract of plant showed the highest activity at resistant Staphylococcus aureus (MRSA). Niger J Pharm [84] 0.2 mg/mL. The IC50 values of the methanol extracts of Sci 2008;7:1-8. leaves and stem bark extract of plant were found to be 56.9 9. Harris BJ, Baker HG. Pollination in Kigelia africana and 13.7 µg/mL, respectively, in MTT assay.[57] Benth. J West Afr Sci Assoc 1958;4:25-30. 10. Hoyo JD, Elliott A, Sargatal J. Handbook of the Birds of the World. Vol. 4. Spain: Lynx Edicions; 1997. p. 415-20. CONCLUSION 11. Gabriel OA, Olubunmi A. Comprehensive scientific demystification of Kigelia africana: A review. Afr J Pure K. africana is important medicinal plant which has been Appl Chem 2009;3:158-64. used traditionally for the treatment of various diseases. 12. Gill LS. Ethnomedical uses of Plants in Nigeria. 9th ed. Approximately 149 compounds have been isolated from Benin: University of Benin Press; 1992. p. 275. K. africana belong to iridoids, naphthoquinones, terpenes, 13. Oyedeji FO, Bankole SO. Quantitative evaluation of the terpenoids, limonoids, steroids, coumarins, flavonoids, and antipsoriatic activity of sausage tree (Kigelia africana). phenolics category which have a wide range of biological Afr J Pure Appl Chem 2012;6:214-8. activities. Several experiments of extracts and isolated 14. Singh A, Sharma UK, Sharma U, Sutar N, Misra V, compounds of plant provide meaningful justification of their Yadav G. Anticonvulsant activity of Kigelia pinnata use. Further, clinical study of isolated compounds may be bark extracts. Int J Pharm Pharm Sci 2010;2:147-9. conducted to get potential candidates for the treatment of 15. Chima UD, Ofodile EA, Okorie MC. A survey of diabetes, cancer, malaria, diarrhea, liver disorders, etc. Thus, plants used in the treatment of ante-natal and post-natal K. africana is the plant of choice for future research purposes, disorders in Nneochi Local Government area of Abia and will surely attract the attention of research scholars in the State, Nigeria. Greener J Biol Sci 2013;3:229-37. fields of pharmacology, drug discovery, and phytochemistry. 16. Fouche G, Cragg GM, Pillay P, Kolesnikova N, Maharaj VJ, Senabe J. In vitro anticancer screening of South African plants. J Ethnopharmacol 2008;119:455-61. ACKNOWLEDGMENT 17. Msouthi JD, Mangombo D. Medicinal herbs in Malawi and their uses. Hamdard 1983;26:94-100. Authors are thankful to the librarian, Rajiv Gandhi South 18. Oliver-Bever B. Medicinal Plants in Tropical West Campus, Banaras Hindu University, for providing facility of Africa. 1st ed. Cambridge: Cambridge University Press; literature survey. 1986. p. 388. 19. Azuine MA, Ibrahim K, Enwerem NM, Wambebe C, Kolodziej H. Protective role of Kigelia africana REFERENCES fruits against benzo[a]pyrene-induced forestomach tumourigenesis in mice and against albumen- 1. Picerno P, Autore G, Marzocco S, Meloni M, Sanogo R, induced inflammation in rats. Pharm Pharmacol Lett Aquino RP. Anti-inflammatory activity of verminoside 1997;7:67-70. from Kigelia africana and evaluation of cutaneous 20. Focho DA, Newu MC, Anjah MG, Nwana FA, Ambo FB. irritation in cell cultures and reconstituted human Ethnobotanical survey of trees in Fundong, Northwest epidermis. J Nat Prod 2005;68:1610-6. Region, Cameroon. 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Lazare SS, Rufin MK, Elisabeth MZ, Cedric DJ, inflammatory activities of the ethanolic stem bark extract Valerie M, Geatan H, et al. Antibacterial activity of of Kigelia africana (Bignoniaceae). Afr J Biotechnol crude extracts, fractions and compounds from the stem 2007;6:582-5. bark of Jacaranda mimosifolia and Kigelia africana 38. Koster R, Anderson M, De Beer EJ. Acetic acid for (Bignoniaceae). Pharmacologia 2016;7:22-31. analgesic screening. Fed Proc 1959;18:418-20. 52. Jeyachandran R, Mahesh A. Antimicrobial evaluation of 39. Carey MW, Rao NV, Kumar BR, Mohan G.K. Anti- Kigelia africana (Lam). Res J Microbiol 2007;2:645-9. inflammatory and analgesic activities of methanolic 53. John BS. Comparative antibacterial activity study of extract of Kigelia pinnata DC flower. J Ethnopharmacol Solanum incanum L. J Swamy Bot Cl 2001;18:81-2. 2010;130:179-82. 54. Ankur T, Singh V, Munish B, Kumar A, Thakur K. 40. Fredrick AC, Ebele OO, Chioma BO, Utoh-Nedosa UA. Isolation and anti-bacterial susceptibility testing of multi Analgesic, phytochemical and toxicological drug resistant Pseudomonas aeruginosa causing urinary investigations of ethanol extract of the leaves of Kigelia tract infections. J Chem Pharm Res 2011;3:342-7. Africana (Lam.) Benth (Family Bignoniaceae) - Sausage 55. Binutu OA, Adesogan K, Okogun JI. Antibacterial and Tree. J Pharm Biomed Sci 2014;4:588-95. antifungal compounds from Kigelia pinnata. Planta Med 41. Kamau JK, Nthiga PM, Safari VC, Njagi SM, 1996;62:352-3. Mwonjoria JK, Ngugi MP, Ngeranwa JJ. Antipyretic 56. Hadi S, Bremner JB. Initial studies on alkaloids from properties of methanol stem bark extracts of Acacia Lombok medicinal plants. Molecules 2001;6:117-29.

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International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S31 A review on Samanya Sodhana of Parad

Ashish Kumar Tripathi, Sushma Rawat, K. C. Sharma Department of Rasashastra and Bhaishajya Kalpana, UAU, Rishikul Campus, Haridwar

Abstract

Ayurveda, which has been widely recognized as a system of health care, has its historical roots in the Indian subcontinent. It has been practised in India for more than 5000 years. Glory of Ayurveda is spreading worldwide. Ayurvedic medicines basically are of herbal as well as of mineral origin. According to classics, drugs of herbo-mineral origin, i.e., the rasaushadhis are best in therapeutics. Mercury is backbone of Rasashastra as the whole branch is named after it. However, many questions are now being raised by scientific and non-scientific community worldwide regarding the safety and efficacy of rasaushadhis. Global

REVIEW ARTICLE REVIEW resurgence of Ayurveda has necessitated its scientific validation in terms of both therapeutic efficacy and safety that ultimately depends on the quality control of ayurvedic pharmaceutical processes. Rasashastra has the potential to convert a poisonous substance into therapeutically useful drug after undergoing through a number of processes among which Sodhana is very important. Sodhana in Ayurveda is not only just elimination of undesired substances but also enhances medicinal properties, reduces toxic principles, addition of extraneous properties etc. A lot of methods are mentioned in Rasashastra for paradshodhana, of which the widely used are the sodhana by garlic, lime, and rock salt or by nagavalli, ardrak, and kshartraya. To show the acceptability of parad as a medicine, it is the need of hour to prove that these procedures not only reduce the toxicity but also enhance the therapeutic efficacy. Mercury must be used for medicinal purpose only after preclinical studies, i.e., quality, safety, and efficacy of the drug. A number of researches have been done in this regard. In this study, we have made an attempt to review on such researches to make out the probable outcome of Sodhana of Parad.

Key words: Nagvalli, Parad, Rason, Sodhana

INTRODUCTION and it has quality to easily absorb, the metals, and minerals. For the purification of parad, several methods have been asashastra (science of alchemy) is adopted in the rasa texts. a branch dealing with the study of Rsubstances used as medicines in Ayurveda As Ayurveda is itself a huge science, it does not need any and their detoxification and processing. It deals explanations but to reveal its glory in modern globalised with Parad (mercury) which is considered to be era it’s the need of hour to explain its concepts scientifically the heart of Rasashastra. Rasa Dravyas include according to modern science. So here an attempt has been minerals and metals which are mainly Bhumij made to explain the concept of samanyasodhan of parad on the in origin (obtained from earth), and Parad grounds of modern science based on several scientific research (mercury) is also one among them. articles published in leading journals and publications.

Without shodhan we cannot use any drug in medicine. In the texts of Rasashastra, many MATERIALS AND METHODS purification methods described for metals and minerals. Depending on the toxicity, few are The review centralizes on published research articles in the purified with the general purification (Samanya MEDLINE, PubMed, Google Scholar, Science direct, ASL, shodhana) methods and some with specific (Visheshsodhan) methods. By the purification, Address for correspondence: physical and chemical impurities are removed, Dr. Ashish Kumar Tripathi, Department of Rasashastra and hence, metals are free from toxicity and Bhaishajya Kalpana, UAU, Rishikul Campus, and metals become suitable for the further Haridwar. procedures like Marana. That is why shodhan is very essential for Ayurvedic herbomineral E-mail: [email protected] preparations. Parada is available in liquid state

International Journal of Green Pharmacy • Vol 12 • Special Issue 2018 | S32 Tripathi, et al.: Samanya Shodhan of Parad and Scopus. Study criteria based on research articles and • Ghritkumari, Chitrak, publications related to Parad sodhana, scientific explanations Rakt‑sarshap, Brihati, Trifala of reactions in parad sodhana, and biochemical reactions kashay related to garlic, mercury, lime, salt etc. Method adopted is • Guda (juggery), Trikatu, prospective logical scientific literary research. Yavani, Lavan panchak, chitrak chhal, Trifala, Kshartraya Concept of Sodhan • Lime, Grihdhoom, Haridra, Ishtika churna Before preparation of herbomineral combination, Ayurved Prakash[4] Rason (garlic), purification of metallic substances is necessary to reduce the Raai (Brasicajuncia), Kaanji, concentration of chemicals.[1] It is essential because higher Gwarpatha, Kakmachi, Trifala, concentrated chemical may cause adverse effect on human Saindhav lavan, Nausadar [2] body. Hence, these chemicals should be neutralized to Rasendra Sar • Shrikhand, Devdaru, its normal pharmacological actions. Hence, this shodhan Samgrah[5] Kakjangha, Jayanti, Musali, concept is very important. Ghritkumari • Ghritkumari, Haridra, Kanji The process of eliminating the impurities of the metallic • Gandhak, Jambeeri nimbu substances by means of Svedana (vaporing), Mardana • Jayanti, Erand, Ardrak, (grinding), Prakshalana (performing frequent ablutions), Makoya Galana (straining fluids), Avapa (substances are added into • Haridra, Ishtika churna, Grihdhoom, Trifala, the liquefied metals), Nirvapa (metals are burnt to red hot Ghritkumari, Chitrak, Trikatu and dipped in liquids), Bhavana (levigation), and Bharjana (frying in pan) specific process and techniques with the help Among all these, the widely used methods for samanya of specifically mentioned Aushadha dravya (plant juices or sodhan of Parad are by Rason (garlic), Sudharaj (lime), and animal products) is known as Sodhana. Saindhavlavan (rock salt) or by Nagvalli (betel leaves juice), Ardrak (ginger rhizome juice), and Kshartraya (Yavakshar, Sodhan in Ayurveda is not only elimination of undesired Sajjikshar, and Tankan). substance but also it has some outcomes such as:- • Conversion of metals and minerals into herbomineral/ In the first method, parad is triturated with equal quantity of organomineral compound lime for 3 days and strained through a double-layered cotton • Enhancing/masking medicinal properties cloth, and then, it is further triturated with equal amount • Reducing toxic properties of scraped garlic and rock salt (half of parad) till the paste • Chemical and physical properties get changed becomes black. Then, the blackish paste is washed with water • Extraneous matter is added to impart the therapeutic to get suddha parad. effect into original matter. In the second method, parad is triturated with expressed Samanya Sodhan of Parad (mercury) juice of betel leaves and fresh rhizomes of ginger along with Kshartraya (Yavakshar, Sajjikshar, and Tankana) for 3 days In Ayurveda, various doshas are mentioned in different and washed with Kanji to get Suddha parad. Rasgranthas, observed during the use of Ashodhit parad. It has also mentioned that the shudha parad is not toxic and Explanation of Parad Sodhan possesses roganashak property and acts as medicine. Hence, in the present era, the toxicity of mercury is produced by the Chemical and electrical processes take place on the surface Ashudh form of mercury. Several methodologies have been of mercury. A study shows that even the irradiation effect adopted by Acharyas time to time as per circumstances for of mercury while trituration is suppressed and neutralized parad sodhana: by garlic.[6] Due to churning, surface tension decreases and increment in temperature takes place.[7] Heat produced due Rasagranth Parad Samanya Sodhan by to friction of the pestel and mortar seizes the heat labile Rasatarangani[3] • Sudharaj (lime), impurities. Open trituration in khalva allows atmospheric Rason (garlic), Saindhav oxygen to react within a self-created magnetic field. Mercury lavan (rock salt) interferes with the capacity to quench highly reactive oxygen • Nagvalli (betel), species to form inorganic mercury compounds. Ardrak (ginger), Kshartraya (Yavakshar, Lime is a preferred precipitant for the removal of heavy Sajjikshar, Tankad) metals.[8] The mechanism governing the metal removal

International Journal of Green Pharmacy • Vol 12 • Special Issue 2018 | S33 Tripathi, et al.: Samanya Shodhan of Parad process is determined as chemical precipitation and adsorption iron, copper, zinc, silver, tin, cadmium, lead, and arsenic are at high pH.[9] Unlike the case for many heavy metals, high reduced in concentration while some new elements are added pH does not reduce mercury solubility. Except for cadmium, such as B, Ca, Cr, and Ti. little fraction of copper and lead in the adsorption residues desorbs in acidic media. Hence, lime also provides alkaline media to stabilize mercury and enhance the removal of DISCUSSION copper, cadmium, lead, and other heavy metals. As per the concept of Ayurveda, “even a strong poison can Garlic has been proved as a best antidote for heavy metal be converted to an excellent medicine if processed and poisoning.[10] Hence, processed garlic is augmented with administrated properly.[19] On the other hand, even the most antidote itself. So one step ahead in safety to select it as a useful medicine may become a poison if handled incorrectly.” best drug for sodhana of parad and logically used. Fresh Over time, Ayurvedic practitioners have tried to develop a bulb of garlic contains allin, allicin, and volatile oils.[11] number of traditional methods to convert toxic substances to When garlic is crushed, enzyme alliinase is exposed which useful medicines. It may be justified that traditional system converts allin into its optical isomer Allicine within 10 s.[12] of purification (Śodhana) can influence the physicochemical, Alliicin is unstable (pure Allicine at room temperature has a pharmacological, and toxicological profile of the raw drugs half-life of 2–16 h) and converts readily into mono-, di-, tri-, and thereby useful in increasing safety profile and efficacy and poly-sulfides, sulfur oxide, and other compounds such as of the drugs. It is worthwhile to adopt Sodhana processes ajoene, which is a secondary degradation product of allin, are as per Indian system of medicine in the development of presumably the most active compound responsible for any herbomineral formulations with application of modern multiple bonding along with mercury.[13] technology to assess its safety and efficacy.

Hg+Ajoene (Sulfur oxide) Mercuric sulfuroxide This review discusses the Sodhan procedure of ayurvedic pharmaceutics which is relevant to answer queries regarding Garlic (Allicin-organosulfur) and Hg reaction is a redox. the safety of rasaushadhis. Considering the above concepts, Sulfur and mercury form a best covalent bond, and as a result, this review emphasizes on possible correlation of classical the triturated product turns black in color though many of particulars and researches of contemporary time. We have mercury salts are turned to white powders or crystals. It is a tried to pace with recent advances, and thus, a primitive miniature concept of Kajjali (mercuric sulfide) itself. Hence, theoretical explanation is proposed. Particular drug or media the drug designers of ancient time have proposed parad mentioned for specific methods of sodhana indicate some samanya shodhana using garlic. basic relation between the indicated drug and parad. We can also explain the possible interactions of these organic A give and take principle is followed between mercury and inorganic constituents with Parad on account of surface and garlic. The raw Parad (mercury) contains of iron tension, heat transfer, redox reaction, adsorption, and (4.7800), copper (4.5840), zinc (1.2280), silver (0.304), formation of organometallic compounds. Ultimately, these tin (3.7560), cadmium (2.0534), lead (2.3400), and arsenic are the molecules used for further procedures or therapeutics. (2.6500) elements in ppm levels before the purification.[14,15] After the purification with the help of AAS analysis, the results of elements are iron (2.5760), copper (2.6520), zinc CONCLUSION (0.2800), silver (0.044), tin (1.6090), cadmium (0.1330), lead (0.9036), and arsenic (1.0146) ppm levels.[16] Hence, For the shodhan of Parad, many methods were adopted by above mentioned purification method, the ppm levels in the rasa texts, but most common method described in of these elements are greatly reduced. It also incorporates Rasataraṅgini in which Parad is triturated with equal new elements in Shodhit Parad (new elements such as B, quantity of lime for 3 days and strained through a double- Ca, Cr, and Ti are detected). The selenium and germanium layered cotton cloth, and then, it is further triturated with equal trace elements found in garlic extract[17] are another area of amount of scraped garlic and rock salt (half of parad) till explanation showing some unknowing effect on mercury. the paste becomes black. Then, this blackish paste is washed with water to get suddha parad. Sulfur present in garlic Saindhav lavan (rock salt) consists of 95–98% sodium forms covalent bond with mercury. It causes to potentiate chloride, 2–4% polyhalite (potassium, calcium, magnesium, the therapeutic efficacy besides isolating impurities. After sulfur, oxygen, and hydrogen), 0.01% iodine, and micro the purification, iron, copper, zinc, silver, tin, cadmium, amounts of numerous trace minerals.[18] It also aids the lead, and arsenic in ppm levels reduce and come within the process along with garlic. permissible limits. Some new elements are also added in the final outcome such as B, Ca, Cr, and Ti. When the whole blackish paste is washed with water at the end of the procedure, the mercuric sulphuroxide get hydrolyzed Thus, this method may be explained on the grounds of to produce mercury. In this mercury, heavy metals such as modern science, how scientific methodology has been

International Journal of Green Pharmacy • Vol 12 • Special Issue 2018 | S34 Tripathi, et al.: Samanya Shodhan of Parad developed by ayurvedic experts of those days for making 10. Hughes G. Gamma-glutamyl-S-alkylcysteines in garlic mercury (parad) therapeutically useful by using garlic, lime and other Allium Spp-precursors of age-dependent trans- saindhav. 1-propenyl thiosulfinates. J Nat Prod 1991;54:436-44. 11. Celli MG, Perotto MC, Buraschi D, Conci D. Bioogical and molecular characterization of Garlic virus D and it’s REFERENCES effects on yields of garlic: Acta horticulture. a\Available from: www.actahort.org. 1. Bhagi AK, Chatwal CR. Bioinorganic Chemistry. 12. Skidmore Roth 2003, Schultz et al, 2001.by Armando Mumbai: Himalayan Publishing House; 1998. Ganzalez Stuart. 2. Theil EC, Kenneth NR, Transition metal storage transport 13. Bhagwan Dash RV, Iatro-chemistry of Ayurvediya and biomineralization, Department of Biochemistry, Rasashastra, published by ‘Concept Publishing Company North Carolina, State University. Pvt. Ltd., New Delhi, India. 1994. 3. Rasatarangini SS, Shastri K, editor. Rasavigyaanam. 14. Agarwal SK. Advanced Inorganic Chemistry. Meerut: Pragati Prakashan; 2009. 11th ed. New Delhi: Motilal Banarasidas Publication; 15. Madan RD. Modern Inorganic Chemistry. New Delhi: S. 1979. Chand; 1987. 4. Mishra GS. Madhav Upadhyay’s Ayurved Prakash. New 16. Spence R, Barton J. Stabilization of Mercury in High pH Delhi: Chaukhamba Bharati Academy; 1994. Tank Sludges; 2003. 5. Ramprasad V. Gopalkrishna Bhatt’s Rasendra 17. Pallavi K. TGAMC, BELLARY “Lashuna Sar Sangrah. Mumbai: Khemraj Shreekrishna das shodithaparada- a process standardised lead molecule for Publication; 2015 a non-toxic mercurial therapeutic drug”. 2010. Available 6. Phyto Chemistry of Garlic-in Internet Data. from: palsayurveda.blogspot.com 7. Role of Garlic (Alicin) Rationale in Bioelectromagnetic, 18. Titler RV. Chemical Analysis of Major Constituents Lewis elion-2003, castleman 2001, starck 2001, and Trace Contaminants of Rock Salt. Pennsylvania: Avaliable from: https://www.researchgate.net. Department of EPBWS; 2011. 8. Wichtl M. Herbal Drugs and Phytopharmaceuticals. 19. Shastry PK, editor. Rasa Tarangini by Pranacharya Sri 3rd ed. , Stuttgart, Germany: Medpharm Scientific Sadananda Sharma. New Delhi: Motilal Banarasidas; Publishers; 2004. 2004. 9. Barbooti Mahmood M. Researchgate.net ‘Removal of Heavy metalsusing chemicals precipitation’ in place of ‘Lan castlin and colin 1981. March 2011. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 12 • Special Issue 2018 | S35 AA reviewreview onon safetysafety andand efficacyefficacy ofof KuchalaKuchala

Ashish Kumar Tripathi, Sushma Rawat, K. C. Sharma PG Department of Rasashastra & Bhaishajya Kalpana, UAU, Rishikul Campus, Haridwar, Uttarakhand, India

Abstract

In ancient system of healing, all ayurvedic drug formulations have an inbuilt safety profile, but it is necessary to produce the evidence-based documents for the safety and efficacy of ayurvedic drugs, which mainly depends on quality control of pharmaceutical processes. The branch Rasashastra and Bhaishajya Kalpana provides various techniques forfor thethe purificationpurification and and detoxification detoxification of of drug drug ingredients. ingredients. A greatA great debate debate is emerging is emerging time time to time to time that thethat several the several ayurvedic ayurvedic drugs drugs are notare safe.not safe. The Thefacts facts speak speak that thatthe toxicitythe toxicity and adverseand adverse effects effects of drugs of drugs occur occur due todue avoiding to avoiding or the or negligence the negligence of classical of classical references references of safety of safety and efficacy. and efficacy. Modern Modern pharmaceutical pharmaceutical science science gives

REVIEW ARTICLE REVIEW stressgives stressto the toapplication the application of standard of standard operating operating procedures procedures in the drugin the manufacturing. drug manufacturing. Furthermore, Furthermore, Ayurveda Ayurveda refers “Arefers wise “A physician wise physician may use may the use poisonous the poisonous material material like nectarlike nectar with withfollowing following the properthe proper directions, directions, which which are time-testedare time-tested and safe.”and safe.” Kuchala Kuchala (Strychnos (Strychnos nux-vomica nux-vomica Linn.) isLinn.) a well-known is a well-known poisonous poisonous plant in Indian plant systemin Indian of Keywords:system of medicine. Efficacy It, Kuchala contains, thesafety poisonous substances which may harm to the body if not processed or applied properly. The present paper is an attempt to show under the glimpse of modern scientific researches that even a poisonous drug like Kuchala, if applied abiding ayurvedic guidelines from manufacturing to administration, will be therapeutically efficacious even safe too.

Key words: Efficacy, Kuchala, safety

INTRODUCTION less toxic potency.[4] Although the plant Kuchala is described under the “Upavisha varga” (sub poisonous group), it’s he medicine in the present era is much seeds have been used successfully in different formulations advanced and evidence-based. Ayurveda to combat different diseases after proper Shodhan sanskar Toffers a unique opportunity to evolve a (processing of purification). science of healthy, harmonious, and long life. Its holistic approach to health and disease, involving body, mind, and spirit, can provide a broader framework to understand research KUCHALA data emerging from reductionist biomedical sciences. A fresh perspective on the scope Scientific Classification[5] of scientific research on the basic concepts of Ayurveda came from a decadal vision Kingdom: Plantae Subclass: Asteroids document highlighting the importance of Subkingdom: Tracheobionta Order: Gentianales Ayurvedic biology.[1] Kuchala (Strychnos nux- vomica Linn.), a well-known plant in Indian Super division: Family: Loganiaceae system of medicine is being used extensively Spermatophyta in different classical formulations with great Division: Angiosperms Genus: Strychnos therapeutic significance. It has been stated Class: Eudicots Species: S. nux-vomica L. categorically that strong poisons could be the best medicine, if it is used after proper In Ayurveda: Sthavara Vanaspatik vish, Upavisha,[6] phala detoxification (shodhan), in proper therapeutic visha (beeja visha).[7] dose and formulation. On the contrary, a good medicine may affect adversely unless it is In Modern medicine: Neurotoxin spinal excitant poison.[8] used for a proper person in the proper dose.[2] Rasratnasamucchaya described 11 number of Upavisha.[3] Upavisha is the group of drugs Address for correspondence: which were less toxic in nature and not so Ashish Kumar Tripathi, PG Department of Rasashastra & lethal but produce certain toxic symptoms on Bhaishajya Kalpana, UAU, Rishikul Campus, Haridwar, consumption or administration. They are having Uttarakhand, India. E-mail: [email protected]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S36 Tripathi, et al.: Safety and Efficacy of Kuchala

Major chemical constituents:[9] hydroxy 3 methoxy strychnine were new alkaloids found • Brucine in heat-treated samples.[12] Oral dose of 30–50 mg seeds are • Strychinine toxic in nature while 60–125 mg dose of suddha (purified) • Vomicine seeds is recommended. • Kajine and novocain (N-methyl pseudobrucine) • Strychnine and isostrychnine Thus, if Kuchala is used in formulations after the proper • Cuchiloside sodhan procedure, in proper dose as per Ayurvedic classics, • Loganic acids. then it is quite safe.

Safety of Kuchala Efficacy of Kuchala Kupeelu (S. nux-vomica Linn.) is described under the “Upavisa Varga” (semi-poisonous group),[10] and its seeds Seeds of S. nux-vomica were used as a nervine tonic, have been used successfully in the cure of many diseases alexiteric, aphrodisiac, anthelmintic, digestive, purgative, [11] after proper Shodhana. and stimulant. Detoxified S. nux-vomica seeds used in various ayurvedic drugs such as Agnitundi vati, Navjeevan Rasa, and Although 16 alkaloids have been separated and identified Vishatinduka vati as an important ingredient.[17] Ayurvedic from crude nux-vomica, 80% of them are strychnine and properties of Kuchala are as follows:[18] brucine and their derivatives such as isostrychnine and [12] brucine N-oxide. The major chemical constituents of Rasa: Katu Ttikta, Guna: Rruksha, Laghu, Teekshna, nux-vomica (strychnine and brucine) have been reported Veerya: Ushna, Vipaka: Katu Doshaghanata: for their adverse effects.[13] The specific sodhana procedures Kaphavatshamak[19] Kaphapittanashanam[20] Rogaghnata:[21] mentioned in Ayurvedic classics reduces these alkaloids and Sandhivata, Amavata, Vrana, Kushatha, Nadishoola, establish their values under the safe limit for therapeutic Ardhanga, Gatibhransha, Gyanabhrasnsa, Peshiposha, use. Various research studies show percentage change of Kampa, Badhirya, Ardita, Pakshaghata, Andria, Amadya, strychnine and brucine [Table 1] alkaloids of shodhit seeds Amashyastha, Amadosha, Grahani, Udarshoola, Arsha, of S. nux-vomica. It shows that cotyledon portions contain Krimi, Raktavikara, Vatarakta, Hridyashaithilaya, a higher percentage of strychnine than that present in seed Hridayodara, Kasa, Phuphusshotha, Dhwajabhangha, coat for the entire sample except for the milk purified seeds. Purification with milk markedly reduces the toxicity of crude Sheeghrapatana, Daurbalya, Kushtha, Kandu, Atisweda, nux-vomica than the sample treated with Ghrita.[14] Vishamajwara, and Visuchika. Karma: Sothahara, Puthiyara, Vedanasthapana, Uttejaka, Nadibalya, Deepana, Pachana, Grahi, Shoolprashamana, Hridyottejaka, Kaphaghna, It has been reported that LD50 values of the seeds treated with different processing methods ranged from 2.18 to Kasahara, Vajikarana, Balya, Katupaushtika, Kushthaghna, 2.57 mg/kg (in the mouse), while that of the unprocessed Kandughana, and Swedapnayana. seeds was 1.21 mg/kg. Thus, the processing of S. nux-vomica decreased the toxicity down to one half that of the unprocessed Either S. nux-vomica or its alkaloids have been reported substance. On heat treatment, the contents of the major for their analgesic, anti-inflammatory,[22] antioxidant,[23] antitumor,[24] anti snake venom,[25] antidiarrheal,[26] and alkaloid Strychnine (C21H22N2O3) and Brucine (C23H26N2O4) declined significantly[16] (appx. 63%) with an increase in the hepatoprotective[27] activities in different modern literature. amount of isostrychnine, isobrucine, strychnine –N-oxide, and brucine N-oxide. The cleavage of an ether linkage and the occurrence of N-oxidation have been demonstrated by CONCLUSION heat treatment of authentic strychnine and brucine isolated 16 alkaloids from heat treated and untreated seeds of nux- Kuchala is a well-known spinal poison to modern science. It vomica. Isobrucine N-oxide, isostrychnine -N-oxide, and 2 is used in Ayurvedic pharmacopeia from the ancient period. Ayurveda texts such as Rasa tarangini, Rasratnasamucchaya, Raj Nighantu, and Bhavaprakasha mentioned detail Table 1: Percentage of strychnine and brucine in crude and purified seeds of Strychnos nux-vomica[15] description of the plant, basic properties, sodhan methods, therapeutic uses, and indications. As Acharya Charak in Strychnos nux-vomica seeds % of % of Sutrasthan 1st chapter verse, 127 says, with a judicious strychnine brucine planning deadly poison could be used as an effective Crude form 1.92% 0.93% medicine, while a misuse of a life-saving drug results in a Seeds after purified with 0.96% 0.19% deadly poison. Hence, if Kuchala is used with mentioned Gomutra standards for raw material, processing’s and with proper Goghrtia fried seeds after 0.068% 0.012% diagnosis in suitable prescribed dose, then it is safe as well purification by Gomutra as efficacious too.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S37 Tripathi, et al.: Safety and Efficacy of Kuchala

REFERENCES 16. Bhanu MN, Vasudevan TN. Studies on Purification of Nux-vomica. Ind Drugs 1989;26:150-2. 1. Valiathan MS. Ayurvedic Biology-A Decadal Vision 17. Lavekar MB, Yelne PC, Sharma TJ, Dennis MM, Document. Bangalore: Indian Academy of Sciences; Padhi GV, Joseph S. Data Base on Medicinal Plants 2006. Used in Ayurveda and Siddha. Vol. 5. New Delhi: 2. Agnivesh. Charak Samhita, Edited by Vaidya Yadavji Central Council for Research in Ayurveda and Siddha; Trikamji Acharya. Varanasi: Chaukhambha Surabharti 2008. p. 140. Prakashan; 2008. 18. Lavekar GS. Database on Medicinal Plants Used in 3. Ambikadatta S. Suratnojivala Hindi Commentry, Ayurveda and Siddha. Vol. 5. New Delhi: CCRAS; Rasaratnasammucchaya. 18th ed. Varanasi: Chukhambha 2008. p. 140. Amarbharti Prakashan; 1988. p. 170. 19. Sharma PV. Shodhal Nighantu. 1st ed. Baroda: Oriental 4. Namburi Shekhar UR. A Textbook of Agadtantra. Institute; 1978. p. 125. Varanasi: Chukhambha Sanskrit Sansthan; 2013. p. 16. 20. Mishara B, Vaishya R. Bhavaprakasha, Purwardhwam. 5. Available from: h ttps://www.en.wikipedia.org/wiki/ 8th ed. Varanasi: Chukhambha Sanskrit Sansthana; 1993. Strychnos_nux-vomica. [Accessed on 2018 Feb 02]. p. 568. 6. Shastry PK. Rasatarangini. 11th ed. New Delhi: Motilala 21. Sharma P. Dravyaguna-Vigyana, and Part. Varanasi: Banarasidas; 1979. p. 675. Chukhambha Bharti Academy; 2005. p. 85. 7. Ambikadatta S, editors. Sushrutsamhita-klp.3/3. 22. Yin W, Wang TS, Yin FZ, Cai BC. Analgesic and Varanasi: Chukhambha Sanskrit Sansthan; 2000. p. 16. anti-inflammatory properties of brucine and brucine 8. Singhal SK. Toxicology at a Glance. 7th ed. Mumbai: N-oxide extracted from seeds of Strychnos nux-vomica. The National Book Depot; 2009. p. 114. J Ethnopharmacol 2003;88:205-14. 9. Shastry JL. Dravyaguna Vijnana. 3rd ed., Vol. 2. Varanasi: 23. Tripathi YB, Chaurasia S. Effect of Strychnos nux- Chukhambha Orientaliya; 2008. p. 353. vomica alcohol extract on lipid peroxidation in rat liver. 10. Sharma SN, Shastri KN. Rasa Tarangini. 11th ed. Pharm Biol 1996;34:295-9. New Delhi: Motilal Banarasidas Publication; 2000. 24. Deng XK, Yin W, Li WD, Yin FZ, Lu XY, Zhang XC, p. 163-4. et al. The anti-tumor effects of alkaloids from the seeds 11. Gogte VM. Ayurvedic Pharmacology and Therapeutic of Strychnos nux-vomica on hepG2 cells and its possible Uses of Medicinal Plants. 1st ed. Mumbai: Bharatiya mechanism. J Ethnopharmacol 2006;106:179-86. Vidya Bhavan; 2000. p. 345-7. 25. Chatterjee I, Chakravarty AK, Gomes A. Antisnake 12. Cai BC, Hattori M, Namba T. Processing of venom activity of ethanolic seed extract of Strychnos Nux-vomica. II. Changes in alkaloid composition of nux-vomica Linn. Indian J Exp Biol 2004;42:468-75. the seeds of Strychnos nux-vomica on traditional drug- 26. Shoba FG, Thomas M. Study of antidiarrhoeal activity processing. Chem Pharm Bull (Tokyo) 1990;38:1295-8. of four medicinal plants in castor-oil induced diarrhoea. 13. Nadkarni KM. Indian Materia Medica. 13th ed., Vol. 1. J Ethnopharmacol 2001;76:73-6. Mumbai: Popular Prakashan; 1976. p. 1175-11. 27. Gopalkrishna SV, Narasu ML, Ramachandra SS. 14. Agrawal VK, Joshi D. Effect of purifications (Shodhan) Hepatoprotective activity of detoxified seeds of

on the alkaloidal concentration of a. Kuchala seeds. Nux‑vomica against CCl4 induced hepatic injury in J Res Indian Med 1977;12:41-6. albino rats. Pharmacologyonline 2010;1:803-15. 15. Neetu, Singhal HK, Sharma KC, Sharma CP. Importance of drug safety and Efficacy w.s.r. to S. nux-vomica detoxification. J Homeopathy Ayurvedic Med 2013;2:2. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S38 The concept of blood circulation in Ayurveda

B. M. N. Kumar Department of Rachana Sharir, RGSC, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

The knowledge of blood circulation, according to western scholars, came into existence in 1628 AD by William Harvey and was developed by Malphighi in 1661 AD. However, ancient Ayurvedic Acharyas knows very well about the circulation of rakta-rasa (plasma) and rakta (blood) from the samhita period. Bhela is the first ayurvedic acharya to explain the blood circulation in a systemic way. Rasa and rakta are the first two dhatu in the sequence of seven dhatu, and rakta dhatu is produced from the nutrient portion of rasa dhatu. Sushruta described that

REVIEW ARTICLE REVIEW hrudaya is seat of the rasa, and from the hrudaya, it travels through 24 dhamanis and nourishes the entire body constantly. Bhela has described the systemic circulation explicitly. He said, “The blood (rasa) is first ejected out of the heart, it is then distributed to all parts of the body, and thereafter, is returned to the heart through the blood vessels known as “sira.” The Ayurvedic acharyas said that the site of vyana vayu is hrudaya (in the heart) and the function of vyana vayu is rasa samvahana (circulation of liquid tissues in the whole body). The whole physiology of parivrtti or paribhramanam or circulation of rasa and rakta dhatus executes by vyana vayu by its vikshepocita karma or pushing and pumping function through anatomical structures - hrudaya (heart), sira, dhamani (both may include in ten great vessels or sira), and sravana karma of srotas (minutest channels or capillaries) which are prasrata or spread from mulatkhadantara (hrudaya or heart) in a appropriate manner.

Key words: Bhela, circulation, rakta, Rasa, sira

INTRODUCTION produced from the nutrient portion of rasa dhatu.[2] The term Rasa is derived from “Gatyarthak Rasa Dhatu” depicting he concept of blood circulation described its meaning that it moves throughout the day and night.[3] in Ayurveda is amazingly accurate to the Sushruta described that hrudaya is the seat of the rasa, and modern concept of blood circulation. from the hrudaya, it travels through 24 dhamanis and T nourishes the entire body constantly. The vruddhi and kshya Our acharyas are very well known about blood circulation and its purpose, i.e., carrying of of this rasa cause abnormalities in the body.[4] prana (oxygen technically) and rasa (nutrients) to the entire body in a cyclical manner with the The essence of food known as ahara rasa is formed first heart acting as a pump to carry out this function by the action of jatharagni in the amasaya and is partially long before William Harvey discovered the digested product. Then, it enters in pacyamanasaya, and there, circulation of blood in the 17th century. it undergoes further digestion by the action of bhutagni and formed rasa dhatu.[5] Rakta is formed from the ahara rasa.[6] The literary material related to blood circulation has been collected from different sthanas (parts) According to Sushruta food composed of pancha of Ayurveda samhitas and modern anatomy mahabhutas of four kinds of ahara, which composes of six books such as Chaurasia general anatomy tastes in combination with two types of virya and eight types and Gray’s anatomy critically reviewed and of virya and showing the effect of twenty gunas which will correlated with modern terms. undergoing paka and get separated as sara and kitta bhaga, the sukhsma amsa of this sara bhaga which is composed of prasada bhaga is known as rasa.[7] REVIEW OF LITERATURE Address for correspondence: B. M. N. Kumar, Department of Rachana Sharir, RGSC, Formation of Rasa and Rakta Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. Rasa and rakta are the first two dhatu in the E-mail: [email protected] sequence of seven dhatu,[1] and rakta dhatu is

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S39 Kumar: Circulation of rakta

Sushruta in sutrasthana 14th chapter Shonita varnaniya is clear and colorless, so it refers to plasma; Rakta can be adhyaya said that the apya rasa after reaching yakrut and taken as red blood cells, as it is said to be of red color such pliha obtains red color by the tejas and becomes rakta dhatu. as Gunjjaphala (fruits of Abrus precatorius) and Padma This rakta flows in siras and maintains life activities.[8] (Nelumbo nucifera),[19] whereas the white blood cells can be considered as shonitarupi oja. According to Sharangadhara, the essential substance of the food material is formed into rasa. Rasa reaches hrudaya with Rasa, in its entirety, is not converted into rakta, only that the help of samana vata. There, it undergoes the process of fraction of its which is homologous to rakta is turned into further digestion with the help of pitta and gets colored to this dhatu. The remaining portion of rasa is generally spoken become rakta. This rakta exists all over the body and is the as rakta as it assumes red color, while passing through rakta best supporter of life.[9] sthanas. The obvious difference between the rasa dhatu and rakta dhatu is like the difference between plasma and erythrocytes on the one hand, and the blood and lymph, on

Parvrtti or Paribhramanam of Rasa and Rakta the other hand. It is, in this sense, that plasma (including the (Blood circulation) interstitial fluid and lymph) would appear to be the analog of the rasa dhatu as described in Ayurveda. It is seen from Bhela has described the systemic circulation explicitly. He Sushruta samhita that the term Rasa is derived from the said, “The blood (rasa) is first ejected out of the heart, it is Sanskrt root “Rasa” - to go, and the rasa dhatu of the body then distributed to all parts of the body, and thereafter, it is is so-called because of the fact that it continuously flows returned to the heart through the blood vessels known as [10] through and permeates every vital principle of an animated sira. organism. In addition, it is the rasa dhatu, the analog of plasma, which is the source of all body secretions.[20] Acharya Sharangadhara has mentioned that urah (thorax) is [11] a reservoir of the blood. The sira originates from the heart At the level of hrudaya, dhamanis, and siras, it forms part form a closed circuit. The blood (rasa) ejects away from the of the circulating rakta, from which latter, it separates, at heart to the all over the body in the influence of vyana vayu the level of srotamsi, to return back into hrudaya. Hence, in and then returns back through the sira similar as rivers with modern, it is related to blood, plasma, interstitial fluid, and [12] ultimately drains their water in a sea. lymph.

Chakrapani stated that term rasa includes all circulating Blood is a transitory but a vital constituent, dhatu of the body, [13] fluids along with Rakta. Vagbhatta has further clarified transitory in the sense that it is always replenished and is ever that it is not only the Rasa but also “Rasatmak Ojas” that on the move. Its flow never ceases as long as life exists. Its circulates in the whole body through ten great vessels that initial is in the food that we take, for it is nothing but the [14] directly emerge from hrudaya which circulates throughout essence of the food that is transmuted by the rasa kriya or the entire body ceaselessly for 24 h by yana vayu and it the chemical action of the food. It gets its color in the region [15] provides nutrition to other dhatus or body. of the liver, commences its distribution from the lotus like heart, and courses all over the body through the major and the Sushruta samhita has given examples to describe the pattern minor ramifications of the vessels. In this way, it nourishes of circulation. Rasa propagates in the body in a pattern that is the whole body.[21] similar to the movement of shabda, arci, and jala.[16] According to Vagbhatta, the site of vyana vayu is hrudaya (in the heart),[15] and Charaka and Sushruta have stated that DISCUSSION the function of vyana vayu is Rasa samvahana (circulation of liquid tissues in the whole body). It is actively involved in the Blood is a connective tissue which is in fluid form. Rasa and blood circulation, diffusion of blood into the tissue spaces, rakta dhatu altogether can be considered as blood, as both are and perspiration. It also controls the voluntary movements of liquid and circulating in intravascular compartment. While the skeletal muscles.[22] describing the circulation of rasa by the action of vyana vayu (a subtype of vata dosha), Chakrapani has explained In Ayurveda Sutra (a work of 15th century), the circulating the term rasa as “Rasateeti raso dravadhatuuchayate rakta is a complex substance, being composed of a fluid taenrudhiraadinaamapi dravaanam grahanam bhavati,” part, the sthayi rasa dhatu (plasma-serum) and sthayi rakta where the term rasa stands for intravascular circulating dhatu (the formed elements of the blood - the erythrocytes), fluid (drava), i.e., plasma including the blood cells.[17] Bhela which latter, being relatively more predominant among has also used word rasa while describing the circulation of the circulating formed elements, confers on its vehicle, the rasa in heart and blood vessels. Again, the term rasa-rakta characteristic crimson red color. The rasa dhatu transports has been used for the completely digested essential and not only the sthayi or poshya rakta dhatu but also the minutest material (nutrients absorbed in the blood).[18] Rasa remaining poshaka or asthayi dhatus to nourish the poshya

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S40 Kumar: Circulation of rakta sthayi dhatus and the malas cleared from latter. At the level Following points indicate microcirculation of body, different dhatuvaha srotamsi, it is the sthayi rasa dhatu that exudes velocities of blood at different places, and pumping in all or permeates through the ayanamukhas (capillary pores), directions. carrying with it the poshaka dhatus (tissue nutrients), and for the nourishment of poshya dhatus, the sthayi rasa dhatu 1. It is a constant and perpetual activity without any does not permeate through ayanamukhas of the dhatuvaha– obstruction forever (ajasram or avisrantam).[13] srotamsi but performs its vital functions jivanam by giving 2. It is a life process (sada or ceaselessly or always, up the oxygen it carries for the use of poshya dhatus.[23] continually, without stop for the whole life).[13] 3. It is a cyclic process (cakravat).[13] The whole physiology of circulation of rasa and rakta dhatus 5. Sushruta samhita has given examples to describe the executes by vyana vayu by its pushing and pumping function pattern of circulation. Rasa propagates in the body in a through anatomical structures like hrudaya, sira, dhamani pattern that is similar to the movement of shabda, arci, and srotas. These structures are spread from mulatkhadantara and jala. Dalhana quotes that this circulation is reached (hrudaya) in an appropriate manner.[24] to anu srotas or microcapillaries. The circulatory process is compared with shabda or sound to indicate that sound The circulation of rasa and rakta dhatus contains few reaches to any depth in any direction. It is compared peculiarities as described by acharyas, these are listed as with arci or flames to indicate upward. It is compared follows: with jala or water or liquid to indicate downfall means 1. One of the chief functions of hrudaya is to pump or downward direction. Different kind of velocity is also circulate rasa sarvatah or everywhere in the entire body, indicated here. The sound is faster than flames and and from there, it ultimately returns to hrudaya, i.e., as a flames are faster than waterfall. Hence, circulation is in closed circuit.[25] all directions in the body and is maintained at different 2. “Rasa” that is pumped from hrudaya is in the form velocities. Dalhana further adds that these three types of anu or most minute and essential form of properly of movement of rasa are directly related to the status of agni, i.e., tikshna, sama, and manda and ultimately digested ahara formed after the proper action of agni. to the duration of production of dhatu.[28] Gayadasa in The minutest and the essential fraction of properly his commentary said that arci, sabda, and jala types digested food are called “sara” in this context. Thus, it of Rasa flow are present in dhamani, sira, and srotas, is “rasa”. This “sara” includes all completely digested respectively. materials absorbed from the alimentary canal that “rasa” 6. This concept of Sushruta of rasa movement can be is “paramasukshma” meaning that Rasa can follow very explained on the basis of mean flow velocity. As per the minute channels.[7] view of different commentators, the velocity with which 3. Paribhramanam or circulation of rasa is in the body in sound moves is greater than that of fire, whereas the a cyclical order or in a closed circuit. Charaka samhita velocity of fire is greater than that of water. The mean provides two important adjectives. flow velocity of blood is maximum in the aorta, as aorta a. One is continuous (samtatya) is the smallest cross-sectional area which receives the b. and other is cyclical (cakravat) entire output of the blood from the heart. This mean Commentators explained the meaning of word cakravat as flow velocity decreases as the blood moves down the vikshepana and samharana. Further, he explained that the cardiovascular system into the arterioles and is lowest meaning of vikshepana is a process of Rasa pumped out of in capillaries. Hence, the movement of Rasa is similar to the heart and samharana is a process of rasa coming toward the movement of sabda, arci, and jala.[29] the heart. Vyana vayu is chief executor of paribhramanam 7. Vagbhatta describes that siradi is mahamula, i.e., they or circulation of rasa. Contraction and relaxation of the are having the more cross-sectional area at the base [17] muscular tissues are also performed by vyan vayu. Entity, and becomes narrower and divides as they move which executes the function of pushing and pumping away.[25] Sushruta also in the same view that as dhamani inappropriate manner, is known as “vikshepa karma” of propagates becomes narrower and divided into hundreds vyana vayu. This circulation is accomplished in the entire to thousands of branches so that looks like gavakshita, body, simultaneously flown ceaselessly, all the time all the i.e., network like.[30] way. This rasa dhatu nourishes all the dhatus.[26] 8. Annarasa, as derived from the food, contains all dhatu poshaka dravyas and circulates along with the rasa- 4. Circulation of rasa rakta happens due to parivrtti. Pari rakta complex to nourish all tissues of the body. This means circulating entire area. Vrtti means Asthitvam and combination of annarasa and rasa dhatu contains a Jivanam means maintenance of health and vitality. The large number of proteins maintaining the colloidal vyana vayu maintains this circulation effectively by its osmotic pressure. The osmotic pressure of the proteins five-fold activities, namely, contraction, relaxation, and regulates the distribution of fluid between the blood ejection of rasa dhatu in upward, downward, and horizontal and tissues. The plasma also contains large quantities of directions.[27] both inorganic and organic ions. The intracellular fluid

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is very different from the extracellular fluid, which is a Commentary by Atrideva Gupta. Ref.no. 6/27. Varanasi: combination of intracellular fluid and the fluids of the Krishnadasa Academy; 1993. p. 56. blood plasma. The extracellular fluid supplies the cells 6. Agnivesa. Caraka Samhita Chikitsasthana, Ayurveda with nutrients and other substances needed for cellular Dipika Commentary of Cakrapanidatta edited by function. Capillaries are the place where the most Yadavaji Trikamji. 5th ed. Ref.no.15/28. Bombay: purposeful function of the circulation, i.e., interchange Nirnaya Sagara Press; 2001. p. 196. of nutrients and cellular excreta between the tissues and 7. Sushruta. Sushruta Samhita Sutrasthana, Ayurveda the circulating blood occurs regularly by the pressure Tattvasandipika Hindi Commentary by Dr. Ambikadatta in the capillaries. However, osmotic pressure caused Shastri. 11th ed. Ref.no. 14/14. Varanasi: Caukhambha by the plasma proteins tends to cause fluid movement Sanskrit Bhavana; 1997. p. 239. by osmosis from the interstitial spaces into the blood, 8. Sushruta. Sushruta Samhita Sutrasthana, Ayurveda preventing the continual loss of fluid volume from the Tattvasandipika Hindi Commentary by Dr.Ambikadatta blood. The maintenance of an optimum blood volume Shastri. 11th ed. Ref.no. 14/5. Varanasi: Caukhambha is essential for the regulation of the cardiac output and Sanskrit Bhavana; 1997. p. 235. the arterial pressure. Decreased blood volume leads to 9. Saranghadhara. Saranghadhara Samhita Purvakhanda, decreased cardiac output. When the cardiac output falls Translated by Himasagar Candra Murthy. 2nd ed. Ref. low, the tissues begin to suffer the nutritional deficiency. no. 6/10. Varanasi: Caukhambha Bharathi Sanskrit This movement of the fluid affected by the osmotic Series Office; 2007. p. 78. pressure maintains not only the fluid volume of the 10. Sharma PV, editor. Bhela Samhita Sutrasthana, plasma but also the function of the heart.[31] Translated and Commented by Krishnamurthy KH. Haridas Ayurveda. Ref.no. 20/3. Varanasi: Chakhambha Now, it is clear that the above descriptions are very much Visvabharati; 2008. p. 123. similar to the modern view of circulation. 11. Saranghadhara. Saranghadhara Samhita Purvakhanda, Translated by Himasagar Candra Murthy. 2nd ed. Ref. no. 5/7. Varanasi: Caukhambha Bharathi Sanskrit Series CONCLUSION Office; 2007. p. 73. 12. Saranghadhara. Saranghadhara Samhita Purvakhanda, On the basis of above discussion, the rasa and rakta dhatu Translated by Himasagar Candra Murthy.2nd ed. Ref. can be considered as blood because they both are in liquid no. 5/78. Varanasi: Caukhambha Bharathi Sanskrit (drava) state, which gets circulated in the intravascular Series Office; 2007. p. 76. compartment (heart and blood vessels) and has functional 13. Agnivesa. Caraka Samhita Chikitsasthana, Ayurveda similarities. It is distributed to all throughout the body Dipika Commentary of Cakrapanidatta edited by due to the action of vyana vata on heart and blood vessels Yadavaji Trikamji. 5th ed. Ref.no.15/36. Bombay: (cardiovascular system), quite similar to blood, and there are Nirnaya Sagara Press; 2001. p. 198. great similarities at the functional level too. The rasa–rakta 14. Vaghbhata. Ashtanga Hrudaya Sharirasthana, English dhatu carries all the nutrients along with oja and nourishes Translation by Prof. Srikantha Murti. 2nd ed. Ref. and protects all the tissues. no. 3/13. Varanasi: Krishnadasa Academy; 1997. p. 46. 15. Vaghbhata. Ashtanga Hrudaya Sutrasthana, English Translation by Prof. Srikantha Murti. 2nd ed. Ref.no. 12/6- REFERENCES 7. Varanasi: Krishnadasa Academy; 1997. p. 103. 16. Sushruta. Sushruta Samhita Sutrasthana. Ayurveda 1. Vaghbhata. Ashtanga Hrudaya sutrasthana, English Tattvasandipika Hindi Commentary by Dr. Ambikadatta translation by Prof. Srikantha Murti. Ref.no. 1/13. 2nd ed. Shastri. 11th ed. Ref.no. 14/16. Varanasi: Caukhambha Varanasi: Krishnadasa Academy; 1997. p. 11. Sanskrit Bhavana; 1997. p. 238. 2. Sushruta. Sushruta Samhita Sutrasthana. Ayurveda 17. Sharma RK, Dash B. English Translation and Critical Tattvasandipika Hindi Commentary by Dr.Ambikadatta Exposition Based on Chakrapani datta’s Ayurveda dipika. Shastri. 11th ed. Ref.no. 14/5. Varanasi: Caukhambha 6th ed., Vol. 2. Ref.no. 15/36. Varanasi: Chowkhambha Sanskrit Bhavana; 1997. p. 236. Sanskrita Series; 2000. p. 221. 3. Sushruta. Sushruta Samhita Sutrasthana. Ayurveda 18. Patwardhan K, editor. Reprint edition. Human Tattvasandipika Hindi Commentary by Dr.Ambikadatta Physiology in Ayurveda, Cardiovascular System. Ch. 6. Shastri. 11th ed. Ref.no. 14/13. Varanasi: Caukhambha Varanasi: Chaukhmbha Orientalia; 2013. p. 36. Sanskrit Bhavana; 1997. p. 239. 19. Agnivesa. Caraka Samhita Sutrasthana, Ayurveda Dipika 4. Sushruta. Sushruta Samhita Sutrasthana. Ayurveda Commentary of Chakrapanidatta edited by Yadavaji Tattvasandipika Hindi Commentary by Dr. Ambikadatta Trikamji. 5th ed. Ref.no.24/22. Bombay: Nirnaya Sagara Shastri. 11th ed. Ref.no. 14/03. Varanasi; Caukhambha Press; 2001. p. 249. Sanskrit Bhavana; 1997. p. 235. 20. Dwarakanath C. Introduction to Kayachikitsa. 3rd ed. 5. Vaghbhata V. Ashtanga Sangraha Sutrasthana, Hindi Varanasi: Chaukhambha Orientalia; 1996. p. 327, 331.

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21. Krishna Murthy KH. Foundations of Ayurveda. Shastri. 11th ed. Ref.no. 1/17-18. Varanasi: Caukhambha New Delhi: B.R.Publishers; 1999. p. 143. Sanskrit Bhavana; 1997. p. 13. 22. Agnivesa. Caraka Samhita Chikitsasthana. Ayurveda 28. Sushruta. Sushruta Samhita, Sharira Sthana, English Dipika Commentary of Cakrapanidatta edited by Translation and Nibandha Sangraha Commentary of Yadavaji Trikamji. 5th ed. Ref.no.28/9. Bombay: Nirnaya Dalhana by Sharma PV. 3rd ed., Vol. 2. Ref.no. 14/16. Sagara Press; 2001. p. 331. Varanasi: Chaukhambha Orientalia Publishers; 23. Dwarakanath C. Introduction to Kayachikitsa. 3rd ed. 2007. p. 98. Varanasi: Chaukhambha Orientalia; 1996. p. 265. 29. Patwardhan K, editor. reprint edition. Human Physiology 24. Dwarakanath C. Introduction to Kayachikitsa. 3rd ed. in Ayurveda, Cardiovascular system. Ch. 6. Varanasi: Varanasi: Chaukhambha Orientalia; 1996. p. 267. Chaukhmbha Orientalia; 2013. p. 38. 25. Vaghbhata. Ashtanga Hrudaya Sharirasthana, English 30. Sushruta. Sushruta Samhita Sharirasthana, Ayurveda Translation by Prof. Srikantha Murti K.R. 2nd ed. Tattvasandipika Hindi Commentary by Dr. Ambikadatta th Ref.no. 3/18-19. Varanasi: Krishnadasa Academy; Shastri. 11 ed. Ref.no. 9/4. Varanasi: Caukhambha 1997. p. 46. Sanskrit Bhavana; 1997. p. 125. rd 26. Dilipa DN. Sharira Kriya Vijnana. 1st ed. Varanasi: 31. Dwarakanath C. Introduction to Kayachikitsa. 3 ed. Chowkhambha Sanskrita Series; 2006. Varanasi: Chaukhambha Orientalia; 1996. p. 230. 27. Sushruta. Sushruta Samhita Nidanasthana, Ayurveda Tattvasandipika Hindi Commentary by Dr. Ambikadatta Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S43 Collection and residual heavy metal contamination of medicinal plants: Need of cultivation

Daneshwari S. Kanashetti1, Kamal Nayan Dwivedi1, P. S. Byadgi2 1Department of Dravyaguna, I.M.S, B.H.U, Varanasi, Uttar Pradesh, India, 2Department of Vikriti Vigyan, IMS, BHU, Varanasi, Uttar Pradesh, India

Abstract

Collection of herbals from random areas/wild collection causes heavy metals contamination in medicinal plants.

REVIEW ARTICLE REVIEW This is becoming burning issue of current scenario of Ayurvedic medicine because medicines are producing toxic effects on human body. This is affecting the globalization of Ayurveda. In this regard, it’s our responsibility to prevent herbal medicine contamination. Crude drugs should be collected from ideal land. Causes for residual metal contamination should be avoided and prevented by various procedures of soil purification such as bioremediation, solidification, vitrification, and soil washing cultivation is the only permanent solution for this so in current scenario cultivation must be best practiced with various horticulture and agricultural techniques. This paper emphasizes on a collection of medicinal plants, causes and ill effects of heavy metal contamination and its prevention.

Key words: Heavy metal contamination, Cultivation, Soil purification

INTRODUCTION Random collection of plants from the wild environment for the purpose of preparation of Ayurvedic medicine exposes very plant has medicinal properties. more chances for toxication of heavy metals and impurities in From ancient period medicinal plants herbal medicine. Thus, cultivation practice sures the purity of Eare widely used as home remedies for Ayurvedic medicine. About 50,000 various species of plants various diseases and also as food. In the previous from wild are in use, only a few are cultivated. Biological way days, people are widely using herbal medicines of removing heavy metals from soil also provides surety of before inventing synthetic medicines. Global pure herbal medicine. Acharyas explained prashasta bhumi, importance to herbal medicines is increasing desha, kala for proper growth, and collection of crude drugs. because of the presumption that herbs are natural and safe and produce no side effects. More than 80% world population depends on herbal COLLECTION OF DRUGS IN ANCIENT medicine. Nowadays heavy metals are detected PERIOD in most of the medicinal plants beyond the permissible limits. Soil, water, air, and climatic In past days, practitioners have direct contact with conditions play important role intoxication of pharmaceuticals, and some practitioners have their own plants by heavy metals. Plants take food from the pharmacies. They were knowing the identification of plants, heavy metal contaminated soil and water thus they themselves were involved in collecting crude drugs from produce adverse effects on human beings such suitable place, and they were preparing medicine their own. as renal failure, liver damage, and deposition Hence, there was no question of the impure drug. People were in blood vessels some metals such as copper, using organic fertilizers and were not aware of insecticides or zinc, and manganese are vital for formation of pesticides, so there was less chemical contamination to the enzymes and coenzymes, help in respiration soil. and photosynthesis if their quantity increases they affect growth of plants.[1] Lead, arsenic, Address for correspondence: cadmium, and mercury have no physiological Daneshwari S. Kanashetti, Department of and biochemical importance. Medicinal plants Dravyaguna, I.M.S, B.H.U, Varanasi, Uttar are raw materials for Ayurvedic formulations Pradesh, India. Phone: +91-8004244989. for this reason they should be checked for the E-mail: [email protected] presence of heavy metals.

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As per ayurvedic perspective properties of land for the Heavy metals are naturally present in the soil in less amount collection of plants is described as:[2] but are increased by following ways: 1. Shita (coldness), atapa (temperature), vayu, and jala are • Geologic and anthropogenic activities like using according to seasons, not extreme cold not extremely pesticides and insecticides (DDT) presence of chlorinated hot. pesticides is quite common in crude herbal materials, 2. Collected from plane surface (samatala) and Pavitra. mining, and melting of metals. Sewage and Sludge, 3. Having water supply in its south direction. burning of fuels, Burning and Burying of plastics. 4. Free from graveyard, chaitya, devagara, sabhagruha • Use of cultivation expedients like cadmium containing (meeting hall), Shvabrama, valmiki, and ushara (type of dung. soil). • Less water/improper irrigation supply. 5. Having krasha and rohisha (types of grass). • Supply of sewage water to cultivated crops. 6. Soil should be snigdha (unctuous), Krishna (black color), • Industrial wastes are polluting both air and water. Suvarna varna (golden color), and madhura rasa. • Change in soil pH, moisture content, and water-holding 7. Where plugging has not been carried out. capacity. 8. Where there are no big trees. • Hyper- or hypo-climatic conditions have an indirect 9. Sadharana or jangala desha. effect. • Cultivation near an industrial area. Medicines collected from this type of place are considered • Increase in siderophore-producing bacteria which cause to be ideal. heavy metal extraction from soil.

Present Scenario Harmful Effects

Pharmaceuticals are prefer wild collection of crude herbs. • Decreased potency of medicines. There is no proper/genotypic identification. Practitioners • Adverse effects on human body such as carcinogenicity, are not involved in the collection, preparation, or cadmium causes osteomalacia, and lead causes renal quality of medicine. Cultivation of medicinal plants tumors. is not encouraged. Patients are getting ill effects of • Affects respiration, photosynthesis, and growth of plants. contamination. Usage of chemical fertilizers and • Affects nutrient uptake by decreasing the decomposition deforestation is increasing. To contour all this cultivation of organic matter. of herbals should be encouraged, proper soil purification methods have to be adopted. Prevention

Deleterious effects collection of medicinal herb from wild: 1. Bioremediation/phytoremediation (phytoplant, remedium-to • Loss of genetic diversity correct or remove an evil) - it is removal of heavy • Habitat destruction metals from soil using microorganisms (Bacillus • Misidentification subtilis, Pseudomonas putida, Enterobacter cloacae, • Phenotypic variability Mycorrhizal fungi, and bio-precipitation by sulfate- • Extract instability reducing bacteria) or using plants are called • Presence of toxic components and contaminants phytoremediation. It is a non-disruptive method of soil • Extinction of plants. remediation.[4] It is time-consuming and it is affected by climatic and geological conditions.[5] By this method, For this reason, wild collection should be abstained, and heavy meals cannot be removed completely, but the cultivation of medicinal crops is encouraged in healthy land. percentage/ratio of contamination is reduced to become Present cultivation and collection practices cause additional less toxic, easily volatilizable, more water-soluble (can contamination and microbial growth. be removed through leaching) or less water-soluble, and less bioavailable.[4] 2. Biostimulation - addition of organic manure to soil CAUSES OF HEAVY METAL which serves as C source for microorganisms present in CONTAMINATION OF PLANTS the soil, causes growth and activity of microorganisms responsible for remediation process through alteration of The heavy metals that are available for plant uptake are those pH.[6] Biochar is organic material used nowaday.[7] that are present as soluble components in the soil solution or 3. Solidification - it involves the addition of binding those that are easily solubilized by root exudates. Most of the agents to a contaminated material to impart physical/ growth reduction in plants is due to reduced photosynthetic dimensional stability to contain contaminants in a solid activity, plant mineral nutrition, and reduced activity of some product and reduce access by external agents through a enzymes.[3] combination of chemical reaction, encapsulation, and

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S45 Kanashetti, et al.: Need of Cultivation

reduced permeability/surface area. Stabilization (also and microorganisms percentage of heavy metals in soil is referred to as fixation) involves the addition of reagents reduced. Other methods such as solidification, vitrification, to the contaminated soil to produce more chemically and soil washing can also be applied but they are cost- stable constituents.[8] effective and are practiced for commercialization purpose. 4. Vitrification - the mobility of metal contaminants can Focusing research on this issue may improve the safety and be decreased by high-temperature treatment of the efficacy of Ayurvedic medicine. contaminated area that results in the formation of vitreous material, usually an oxide solid. During this process, the increased temperature may also volatilize and/or destroy REFERENCES organic contaminants or volatile metal species (such as Hg) that must be collected for treatment or disposal.[9] 1. Jayakumar K, Rajesh M, Baskaran L, Vijayarengan P. 5. Soil washing - it is a volume reduction/waste Changes in nutritional metabolism of tomato minimization treatment technology based on physical (Lycopersicon esculantum Mill.) plants exposed to and/or chemical processes. With physical soil washing, increasing concentration ofcobaltchloride. Int J Food differences between particle grain size, settling velocity, Nutr Saf 2013;4:62-9. specific gravity, surface chemical behavior, and rarely 2. Shastri SS. Kalpasthana, Charaka Samhita of Agnivesha magnetic properties are used to separate those particles Revised by Charaka and Dridabala. 2009 edition. which host the majority of the contamination from the Varanasi: Chaukhambha Bharati Academy; 2005. p. 1-9. bulk which is contaminant-depleted. The equipment 3. Blaylockand MJ, Huang JW. Phytoextraction of metals. used is standard mineral processing equipment, which is In: Raskinand I, Ensley BD, editors. Phytoremediation of more generally used in the mining industry.[10] Toxic Metals: Using Plants to Clean up the Environment. NewYork, NY, USA: Wiley; 2000. p. 53-70. Need of Cultivation 4. Blaylock MJ, Salt DE, Dushenkov S, Zakharova O, Gussman C, Kapulnik Y, et al. Enhancedaccumulation Encouraging for the cultivation of medicinal plants can of Pb in Indian mustard by soil-applied chelating agents. diminish soil contamination and thus plant contamination Environ Sci Technol 1997;31:860-5. also. Points to be considered before going for large-scale 5. Schmoger ME, Oven M, Grill E. Detoxification of cultivation of medicinal plants: Gardening/growing the arsenic by phytochelatins in plants. Plant Physiol particular plant in small area to check suitability of the plant 2000;122:793-801. to that soil (applying horticulture methods), detection of 6. McCauley A, Jones C, Jacobsen J. Soil pH and organic presence of mineral content in soil, plantation of seeds of matter. In: Nutrient Management Module. Vol. 8. identified plant, organic farming, availability of water supply, Bozeman, Mont, USA, Montana State: University etc., benefits of cultivation include: Extension; 2009. • Biodiversity conservation. 7. Namgay T, Singh B, Singh BP. Influence of biochar • Poverty alleviation. application to soil on the availability of As, Cd, Cu, Pb • Safe and efficacious herbal medicines. and Zn to maize (Zeamays L.). Soil Res 2010;48:638-47. • Potent active principles. 8. Evanko FR, Dzombak DA. Remediation of Metals • Uniform and high-quality product. Contaminated Soils and Groundwater, Tech. Rep. • Prevent extinction of species. Pittsburg, PA, USA: TE-97-01, Groundwater Remediation Technologies Analysis Centre; 1997. 9. USEPA. Vitrification Technologies for Treatment of Hazardous and Radioactive Waste Handbook, Tech. CONCLUSION Rep. Washington, DC, USA: EPA/625/R-92/002, United States Environmental Protection Agency, Office of As per present trend cultivation practices of medicinal Research and Development; 1992. plants should be enhanced and supported. Preventive 10. Dermont G, Bergeron M, Mercier G, Richer-Laflèche M. measures should be undertaken. Organic fertilizers must be Soil washing for metal removal: A review of physical/ used to prevent chemical contamination of soil. Education chemical technologies and field applications. J Hazard regarding the importance of herbal medicine is necessary Mater 2008;152:1-31. to conserve natural resources. Plants growing in the area of contaminated soil have stunted growth and have less potency. Phytoremediation is a biological method using both plants, Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S46 Doctrine of eugenics, euthenics and euphenics in Ayurveda

Deepti Singh1, Shrikant Pandey2 1Department of Kriya Sharir, Jeevak Ayurveda Medical College and Hospital Research Centre, Akauni, Varanasi, Uttar Pradesh, India, 2Department of Siddhant Darshan, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

Traditional Indian medicine has served humanity since antiquity. Eight branches of Ayurveda have touched all the aspects of human life ranging from intra-uterine to geriatric age group to achieve and maintain “total health.”

REVIEW ARTICLE REVIEW Ancient science of India laid the foundation of eugenics, euphenics, and euthenics under the discipline of “Garbha Sharir.” Present work is an attempt to explore the knowledge and ideology of traditional Indian medicine to put positive health in future generations.

Key words: Ayurveda, eugenics, fetus, Garbha Sharir, traditional Indian medicine

INTRODUCTION of different body parts of a fetus, and also they were enough aware about the genetic inheritance of traits from parents to raditional Indian medicine has served progeny. humanity since antiquity. Ayurveda includes basically eight branches and Beeja is known as male and female gametes (shukra and T shonita, respectively). Chakrapani states that beejbhaga is that have touched all the aspects of human life ranging from intra-uterine to geriatric age group a collection of those materials in stri and pumbeeja which is to achieve and maintain “total health.” Ancient meant to generate different body parts in the course of fetal science of India laid the foundation of eugenics, development. euphenics, and euthenics under the discipline of “Garbha Sharir.” Despite essential elements of production of fetus, there are several factors which influence progeny which are Ayurveda advocates following factors as collectively termed as “Garbha utpattikar bhava,” namely, pre-requisite for the production of Garbha, Matrija, Pitraja, Atmaja, Satmyaja, Rasaja, and Satvaja. i.e., fetus-

Ritu, Kshetra, Ambu, and Beeja. Objective

鵍셁वंचतुर㔣車सान्ꄿध्यद㔗र्딃स्यद्वधिपूर्कमI् This work gives emphasis over knowledge and clinical practices of ancient Indian medicine to bring positive health ऋतु啍�配रम्बुीजानांसाम嵍र्दङ्क रोयथा II(Su Sha 2/33) in a future generation.

A healthy fetus is the outcome of the union of proper planning of right time for conception Address for correspondence: (Ritu), healthy uterus (Kshetra), adequacy of Deepti Singh, Department of Kriya Sharir, Jeevak nourishment (Ahar rasa), and healthy male and Ayurveda Medical College and Hospital Research female gametes (Beej). These all components are Centre, Akauni,Varanasi, Uttar Pradesh, India. very essential and qualitative and quantitative E-mail: [email protected] deficit of each of component alone or together will not be able to produce Garbha. Received: 23-01-2018 Revised: 26-02-2018 Our ancient scholars were well known to the role Accepted: 11-03-2018 of genes and chromosomes for the production

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S47 Singh and Pandey: Eugenics and Ayurveda

LITERATURE REVIEW transformations inside the fetal body. Jalamahabhuta unites various divisions of the fetal body to make organization Shukra Dhatu between various parts. Prithvimahabhuta gives the final form of the fetal body, and Akashmahabhuta is engaged in total Shukra dhatu (reproductive material of male) is capable of growth and development of fetal body in mother’s womb.[4] In producing garbha and, is composed of Panchabhuta and six this way, fetus undergoes growth and development in uterus types of Rasa namely madhur,amla, lavana etc. According over 9 months of gestational period, and when hand, foot, to Ayurveda each and every living entity comprises tongue, and various organs are manifested along with sensory panchmahabhuta, and all living individuals are the union of perceptions in the fetus, it is named as “Sharir (body). various manifestations of panchabhuta viz. tridosa, rasa, and guna, etc.; at structural, functional as well as psychological level. Thus, reproductive material of male individual (Shukra PREREQUISITE FOR GOOD PROGENY Dhatu) is said to be composed of panchmahabhuta and six rasa as described in Garbha Sharir.[1] Ayurveda Garbha Sharir states following components as a prerequisite for the healthy and fully developed fetus and its delivery.[5] Artava Shukra sampad - Qualitative and quantitative optimal of male reproductive material. Artava Raja and Shonita are some terms oftenly used Shonita sampad - Qualitative and quantitative optimal of synonymously to represent menstrual blood and ovum.Rajah female reproductive material. in female can be defined as a substance produced from Rasa, Atma sampad - Previous Karma and attributes of Atman having the color of Rakta, flowing every month through the combining during fertilization in the fetus. female genital tract for the duration of 3–7 days, commencing Ashaya sampad - Good health of uterus physiologically and at the age of 12 years, and completely ceasing at the age of anatomically. 50 years. Period of 12 days is called as Artavakala which is Kala sampad - Optimal season and external environment. denoted as that time duration in which Rajah or Artava have Upachar sampad - Incorporation of basic and essential capability to produce fetus if fertilized.[2] “garbhiniparicharya” procedure during whole gestational period. Garbha (Fetus): According to the principle of Ayurveda. Hita Anna - Intake of wholesome food during pregnancy. Developing Garbha in the uterus is the combination of Garbhakala - Delivery of fetus after a complete gestational following components: period. • Shukra and Sonita (reproductive materials of male and female individuals, respectively). Above list represents all factors which are essential for • Atma (Vitality). obtaining a healthy and fully developed fetus. Good quality • AshtaPrakriti (union of avyakt, mahan, ahankar, and sperm and ova will produce a healthy zygote. Various panchtanmatra, due to which whole substance on earth qualitative and quantitative deficits in the reproductive is manifested). [3] material do not result in a fetal form. The current increase • Vikaar (Panchmahabhuta and ekadash indriya). in incidences of infertility owes to improper semen quality and quantity. PCOS, pelvic infection resulting in salpingitis, Thus each of above factor will certainly influence the basic tubo-ovarian abscess, advanced age, etc., are the leading structural, physiological, and psychological aspect of Garbha causes in female infertility. Lack of sex education, lack of Sharir. Among preceding list of factors only sukra and sonita cheerfulness, and satisfaction of mind between spouses are can be attempted to be designed and regulated as par ones also a social and crucial reason.[6] Uterine abnormalities requirement. Rest three factors are inherent and depends on along with infection, hormonal imbalance, and some health previous Karma of the individual as Ayurveda, and other problems like diabetes are the causes of miscarriage.[7] A schools of Indian philosophy believes. study over pregnant women population of Bangladesh found seasonal fluctuations over birth weight and length. Infants born in colder months were found to be shorter than those EMBRYOLOGICAL DEVELOPMENT AND born in hot and dry climatic conditions.[8] Antenatal care ORGANOGENESIS IN GARBHA importantly plays a crucial role in the health of fetus as well as the mother. Identification of health issue in mother and After formation of the fetus, embryological development its treatment, nutrition, immunization, personal hygiene, is started under the influence of panchabhuta which and prevention of birth complication are some basic and were obtained through inherent combinations of parents necessary intervention done during the whole duration of reproductive material in fetus. Vayumahabhuta is responsible pregnancy. Carelessness during antenatal care may result for the division of various body parts along with dosha, in complications during labor, mortality, and morbidity of dhatu, and mala. Agni mahabhuta is responsible for various mother and child.[9] Proper food and regimen practice by the

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S48 Singh and Pandey: Eugenics and Ayurveda pregnant lady is an important component because fetus gets When Traditional system of India (Ayurveda) is interrogated nourishment from mother for its growth and development. with the ideology of Eugenics, we find different sets of A study of maternal nutrition over fetal metabolic profile thoughts. Although there is no terminology like eugenics, is found intake of whole grain increase glucose metabolism described in Ayurveda, there are scattered links which gives and reduce the risk of developing type 2 DM.[10] Delivery of hints of these principles practiced in India. For example, baby at completed 37 weeks of gestation prevent the risk of excellency of four factors (ritu, kshetra, ambu, and beeja) low birth weight, fetal distress, and neurological disorders, for production of fetus has been advocated. Shukra Dhatu etc., and thus assures fully developed and mature outcome is known to have the potential of fetus production and best of pregnancy. treatise on internal medicine, Charak Samhita has devoted four different chapters to achieve qualitative and quantitative excellency of shukradhatu. In author’s view, in Ayurveda, GARBH UTPATTIKARBHAVA AND THEIR Eugenics is not meant to practice selective breeding to have IMPACT OVER FETUS desirable trait in progeny rather it is the science of designing desirable quality of sperm and ova which could give birth to a Ayurveda Garbha Sharir describes following six factors healthy offspring when combining with other three important necessary as well as accessory for production of developed factors (ritu, kshetra, and ambu).[14] and mature fetal outcome and also explores the psychosomatic impact of the same over developing fetus which is as follows:[11] Ellen Richards was first to use the term “Euthenics” which Matruja Bhava - Maternal component give rise to the derived from the Greek word “eutheneo” which means “well development of skin, blood tissue, muscle tissue, heart, root to cause.” Richard in her book, Euthenics: The science of liver, kidney, etc., organs in the fetus. controllable environment (1910) argue benefits of euthenics Pitru Bhava - It includes the development of hairs, bones, principle in following manners[15] teeth, veins, and arteries in fetus. Atmajabhava - It affects form and complexion of body and “Human vitality depends on two primary conditions Heredity voice quality etc. and Hygiene - or conditions preceding birth and conditions SatmyajaBhava - Health, enthusiasm, and good quality of the during life. Eugenics deals with race improvement through reproductive material. heredity, while Euthenics deals with race improvement RasajaBhava - Body and organ development with continuity through the environment. Euthenics precedes eugenics, of life. developing better human now, and thus undoubtedly creating SatvajaBhava - Feeling of happiness or sadness, fear or a better race of human in the future.” courage, calmness, or instability of mind. Ayurveda exclusively believes and trust over euthenics Beside above concept phenomenon of “Dauhrida” in mother principles. A pregnant mother is advised to practice controlled states morbid and mortal effects over fetal growth because environment in terms of diet and regimen because growing of incompletion of maternal desires for particular food fetus lays fully dependent over mother for nourishment and and regimen during pregnancy. During whole months of pregnancy maternal practice of quality at mind and bodily life. Ayurveda describes how mother and child are connected level give same effects over mind and body of the fetus.[12] through rasavahanadi (umbilical cord) and further with apara (placenta) and garbhashaya (uterus) and interplay of mother and child activity affect each other physiology at [16] DISCUSSION body and mind level. After birth controlled environment in terms of proper sanitation, proper education, prevention of Idea of Eugenics was well created by Plato’s Republic contagious disease could lay the child with good health and (c. 378 bce) where selected mating was designed to sound mind and thus “total health.” have desirable traits in offspring and later well adapted in 19th century by Sir Francis Galton, who was inspired Euphenics refers to phenotypic improvements after birth. by Gregor John Mendel’s basic laws of Heredity and later This term was coined by Joshua Lederberg in the early “Social Darwinism” theorycame into existence which 1960s. In 1970 many productive efforts were done to develop believed improvement of human through selective breeding. euphenics as it was speculated as positive form of genetic During the early 1900s, eugenics became a serious scientific engineering. One such success was the use of folic acids study pursued by both biologists and social scientists. containing vitamins during pregnancy to combat neural tube However, after that anti-eugenics voices started when poor defect (spina bifida) which is a continuing application of and economically weak populations were subjected to euphenics principles till date.[17] In author’s view “Garbhini forced sterilization during the period of the 1930s. Now new Paricharya” during the whole gestational period of 9 months eugenics is more oriented to the identification of genetic might be understood to link with euphenics principle as par disorder (e.g., hemophilia) and its treatment.[13] modern science which needs extensive research.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S49 Singh and Pandey: Eugenics and Ayurveda

REFERENCES application of the basic antenatal care principles of good care and guidelines in pregnant women’s antenatal 1. Agnivesha, CharakaSamhita, Hindi Commentary, care records. Afr J Primary Health Care Fam Med Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, 2016;8:1016. Sharirasthana, Atulyagotriyaiyam-Adhyaya. (2; 4). 10. Tzanetakou IP, Mikhailidis DP, Perrea DN. Nutrition Varanasi: Chaukhambha Krishnadas Academy; 2013. during pregnancy and the effect of carbohydrates on the p. 1004. offspring’s metabolic profile: In search of the “Perfect 2. A Study of Certain Autonomic Responses in Maternal Diet.” Open Cardiovasc Med J 2011;5:103-9. Perimenopausal Women wsr to Dosha Prakriti, Singh 11. Agnivesha, Charaka Samhita, Hindi Commentary, Deepti, Thesis, Literature review of Literature Section, Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K. Department of Kriya Sharir, BHU; 2016. p. 8. Sharirsthana, Khuddikagar Bhavkranti Shariram- 3. Sushruta, Samhita S. Ayurveda Tattva Sandipika Hindi Adhyaya (3; 3). Varanasi: Chaukhambha Krishnadas Commentary, Shastri Ambikadutta, Sharirsthana, Academy; 2013. p. 1024. Sharirsnkhya Vyakarana Sharir-Adhyaya (5; 2). 12. Agnivesha, Charaka Samhita, Hindi Commentary, Varanasi: Chaukhambha Sanskrit Sansthan; 2014. p. 54. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, 4. Sushruta, Samhita S. Ayurveda Tattva Sandipika Hindi Sharirsthana, khuddikagar Bhavkranti Shariram- Commentary, Shastri Ambikadutta, Sharirsthana, Adhyaya (4; 15). Varanasi: Chaukhambha Krishnadas Sharirsnkhya Vyakarana Sharir-adhyaya (5; 3). Varanasi: Academy; 2013. p. 1060. Chaukhambha Sanskrit Sansthan; 2014. p. 54. 13. Available from: https://www.britannica.com/science/ 5. Agnivesha, Samhita C. Hindi Commentary, Dwivedi eugenics-genetics. Laxmidhar Dwivedi B.K. and Goswami P.K. 14. Sushruta, Sushruta Samhita, Ayurveda Tattva Sandipika Sharirasthana, atulyagotriyaiyam-adhyaya (2; 6). Hindi Commentary, Shastri Ambikadutta, Sharirsthana, Varanasi: Chaukhambha Krishnadas Academy; 2013. Sharirsnkhya Vyakarana Sharir-Adhyaya (2; 35). p. 1005. Varanasi: Chaukhambha Sanskrit Sansthan; 2014. p. 19. 6. Tabong PT, Adongo PB. Understanding the social 15. Available from: https://www.archive.org/details/ meaning of infertility and childbearing: A qualitative euthenicsscience00richrich. study of the perception of childbearing and childlessness 16. Agnivesha, Charaka Samhita, Hindi Commentary, in northern ghana. PLoS ONE 2013;8:e54429. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K. 7. Available from: https://www.webmd.com/baby/guide/ Sharirsthana, Mahatigar bhavkranti Shariram-Adhyaya. pregnancy-miscarriage. Varanasi: Chaukhambha Krishnadas Academy; 2013. 8. Rashid H, Kagami M, Ferdous F, Ma E, Terao T, 17. Available from: https://www.en.wikipedia.org/wiki/ Hayashi T, et al. Temperature during pregnancy Euphenics. influences the fetal growth and birth size. Trop Med Health 2017;45:1. 9. Ngxongo TS, Sibiya MN, Gwele NS. Evidence of Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S50 A critical review on therapeutic potential of Ashtanga ghrita

Sushmita Majumder1, Dev Nath Singh Gautam2* 1Department of Pharmacy Ayurveda, Ayurvedic Pharmacy Research Laboratory, Rajiv Gandhi South Campus, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Barkachha, Mirzapur, Uttar Pradesh, India, 2Department of Rasa Shastra, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

The world most ancient documented medical science is Ayurveda, which defines that a healthy body cannot

REVIEW ARTICLE REVIEW function without a healthy mind. Hence, for a healthy lifestyle a healthy mind is needed, and from this, the concept of psychosomatic disorders and psychiatric disease evolve. The study was done with the aim to review the central nervous system (CNS) protective and learning and memory enhancing activity of Ashtanga Ghrita. The ingredients of Ashtanga Ghrita have been found to be effective against various CNS disorders such as cerebral palsy, Parkinsonism, Alzheimer’s disease, and epilepsy. In the Ayurvedic literature consumption of Ghrita is highly recommended in the management of psychiatric disorders as it is having lipophilic action and it acts on the brain so it is well established that it can cross the blood–brain barrier. The toxicological analysis showed that the drug to be absolutely safe for use. The contents of Ashtanga Ghrita also possess properties of an effective nervine tonic by means of their endeavor in improving memory and intellect. Thus, Ashtanga Ghrita can prove to be a good learning and memory, CNS, depressant activity, anticonvulsant action, antinociceptive, and anti-amnestic action, its effect on depression and in attention-deficit/hyperactivity disorder children.

Key words: Anti-amnestic attention-deficit/hyperactivity disorder, antinociceptive, Ashtanga Ghrita, cerebral palsy

INTRODUCTION molecular, cellular, synaptic, network, and behavioral levels; in turn, treating a variety of neurological diseases. Ayurveda is a traditional approach to treatment Neuropharmacology is concerned with the interactions of practices by ancient Aryans which is based on neurotransmitters, neuropeptides, neuromodulators, enzymes, Atharva veda, one of the oldest scriptures of receptor proteins, second messengers, cotransporters and Hindu. Ayurvedic medicines are attracting global ion channels in the central and peripheral nervous systems. population to treat and prevent various diseases By studying the interactions of drugs with these targets, and disease conditions by their holistic approach scientists are developing numerous new drugs to treat many to heal since antiquity. It had developed itself different neurological diseases.[1,5] Ashtanga Ghrita is one in all branches and flourished immensely with of the most potential polyherbal ayurvedic preparations time and age. This system had got advantage which is mentioned as compound preparations in Ashtanga [1] over other medicines in many respects. Nature Hridayam[6] has been use in Ayurveda for Vaka (Speech), gifted us a superior gift in the form of medicinal Medha (Intellectual), Smruti (Memory), and Buddhi (Logical plants to humans to maintain a disease free Thinking) enhancement. Ayurveda, the Indian traditional [2] healthy life. The crucial responsibility herbal system of medicine can offer much in this regard if thousands medicine play in the treatment of human was of unexplored combinations are brought into limelight.[3,7,8] identified from the ancient and still in use To carry out literature review of Ashtanga Ghrita with regard in the modern era.[3] The world most ancient to the textual reference and critical analysis. Ashtanga Ghrita documented medical science is Ayurveda, which defines that a healthy body cannot be Address for correspondence: function without a healthy mind. Hence, for Dr. Dev Nath Singh Gautam, Department of Rasa a healthy lifestyle a healthy mind is needed, Shastra, Faculty of Ayurveda, Institute of Medical and from this, the concept of psychosomatic Sciences, Banaras Hindu University, Varanasi – 221 005, disorders and psychiatric disease evolve.[4] Uttar Pradesh, India. Mobile: +91-9450824065. Neuropharmacology deals with the study of how E-mail: [email protected] drugs affect nervous system functions from

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S51 Majumder and Gautam: A critical review on Ashtanga ghrita literature provided scientific evidence so that the information the seed), a hard seed coat and kernel. It had been found can be used for studied further clinically or in animal studies that the seeds contain an essential oil (0.05%), nonvolatile and it can be inculcated as major prescribed medication for terpenoid oil, a dark brown resin (8.6%), essential oil from CNS problems among children and adults both as curative seed 20.15%, and alkaloid (7.4%) substance.[16] In studies, it and preventive medication. found that P. corylifolia has a potent cytotoxic action which was studied on two cancer cell lines and their corresponding multidrug-resistant (MDR) cell lines. Analytical and METHODS pharmacological data suggest that P. corylifolia significantly inhibits proliferation of sensitive and MDR cancer cells Classical texts of Ayurveda as well as PubMed, Medline in vitro, psoralen and isopsoralen are responsible for the database were used for the search of relevant literature and anticancer activity.[17] Some study demonstrates that aqueous research papers. Papers published on the plants used to and solvent extracts of P. corylifolia were antifungal active formulate Ashtanga Ghrita are considered. The keywords against five Aspergillus species tested in vitro condition by used for the search was “Ayurveda,” “Nervous System,” poisoned technique.[18] “Nootropic activity,” and “Memory enhancer,” etc. In vitro analysis, experimental trials, as well as clinical studies, were Brahmi (Bacopa monniera) belong to the Scrophulariaceae included in the review to search out the reported therapeutic family, is creeping small herb with branches, small oblong potential of Ayurveda drugs. Only research articles published leaves, and light purple flowers. Bacopa’s traditional use as in the English language were considered. an anti-anxiety remedy in Ayurvedic medicine is supported by both animal and clinical research. Brahmi extract did not All contents in equal quantity with Cow ghee 4 times that of cause amnesia or side effects related to Lorazepam, instead [19] content and Cow Milk 4 times that of Cow ghee. of that, it has a memory-enhancing effect. B. monniera has potent activity in the amelioration of cognitive disorders, as well as prophylactic reduction of oxidative damage, NT [20] LITERATURE REVIEW modulation, and cognitive enhancement in healthy people. Brahmi has a great role as a neuroprotector. A study was also Ashtanga Ghrita ingredient has eight plants which are Vacha, done on hippocampus of the temporal lobe of epileptic rats Indulekha, Mandukparni, Sankhpuspi, Shatavari, Bramha which involve cortical GABA receptors in temporal lobe soma, Amruta, and Brahmi Table 1.[7] epilepsy, associated mood disorders, spatial learning, and memory deficit.[21] The study concluded that BME treatment potentiates the therapeutic effect by reversing the alterations Bakuchi (Psoralea corylifolia Linn.) in glutamate receptor binding and NMDA R1 gene expression that occurs during epilepsy.[22] The triterpenoid saponins and It belongs to Fabaceae family; it is an endangered and their bacosides are responsible for Brahmi’s ability to enhance medicinally important plant grows throughout India. It nerve impulse transmission. The bacosides help to repair the possesses important activities such as antibacterial, anti- damage caused in neurons by enhancing activity of a kinase, inflammatory, antiplatelet, antitumor, immunomodulatory, synthesis of neurons and restoration of synaptic activity and antioxidants have also been reported.[9-11] In studies its and nerve impulse transmission. The chemical constituent found that supercritical fluid extracts of P. corylifolia at a conc. responsible for the facilitatory effect of Brahmi on learning of 4 µg/ml, 4 µg/ml, 8 µg/ml, and 16 µg/ml show great growth schedules was identified as a mixture of two saponins inhibitory effects against Staphylococcus aureus.[12] Water designated as bacosides A and B.[23] A learning memory study Extract of P. corylifolia at a dose 20 mg/kg/day shows a good on male rats at a dose of 20 mg/kg, 40 mg/kg, and 80 mg/kg effect for anti-oxidative and anti-inflammatory. Ulcerative was done where animals were subjected to spatial learning colitis was induced using DSS in male mice and the dose of (T-maze) and passive avoidance tests. The behavioral study Bakuchi appease hemorrhagic erosion of the colon mucosa[13] shows that the treatment enhances the memory power of the P. corylifolia has Hemolytic and Mutagenic potential as in rats.[24] studies its found that antioxidant activity was shown by all extracts (crude and protein extracts) estimated by percentage Guduci (Tinospora cordifolia) has been extensively studied 1, 1diphenyl-2-picryl hydrazyl radical scavenging activity and reported to have potent immunostimulant action.[25,26] assay[14] Bakuchi seed contains various phytoconstituents In addition, T. cordifolia also found to have an antistress such as corylifolia, corylifolin, corylifolinin, bakuchic in, effect.[27] Ayurvedic literature recommends a rejuvenating psoralidin, isopsoralidin, bavachin, isobavachin, bavachinin, recipe where T. cordifolia being an important constituent bavachalcone, isobavachalcone, 7-O-methyl bavachin, to enhance the memory function.[28] It can be revealed that bavachromanol, corylin, corylidin, corylinal, 4-O-methyl the crude ethanolic extract of T. cordifolia stem possesses bavachalcone, neobavaisoflavone, bavachromene, and significant antinociceptive as well as antioxidant activities. neobavachalcone. These are mainly flavonoids.[15] The fruits The potential of the extract of T. cordifolia as antinociceptive of P. corylifolia consist of a sticky, oily pericarp (12% of and antioxidant agents may be due to the presence of

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S52 Majumder and Gautam: A critical review on Ashtanga ghrita phytoconstituents such as tannins and phenolics and might be bowel complaints. Leaves are rich in ascorbic acid which responsible for its activity and justify its use as a traditional accelerate nervous activity and also good for increasing folk remedy.[29] T. cordifolia is the best remedy for children memory.[39] Its parts used for the medicinal purpose are its suffering from upper respiratory tract infections. The leaves along with the petioles. The standardized extract at aqueous extract of T. cordifolia significantly lowered the 300 mg/kg and 500 mg/kg shows the effect on analgesic and serum cholesterol and moves the High-density lipoprotein antinociceptive and anti-inflammatory agent along with its cholesterol level to a basic value. It also possesses antioxidant, supportive CNS depression effect.[40] Several animal models anti-hyperglycemic, and antineoplastic and also it shows of anxiety and thus provides support to the ayurvedic claim hepatoprotective [30] and anthelminthic properties.[31] There are that C. asiatica has anxiolytic activity. The data reported various phytoconstituents found in T. cordifolia, belonging have an evidence for the anxiolytic activity of the crude plant to different groups such as alkaloids, glycosides, diterpenoid material and may affect certain mediators to reduce anxiety.[41] lactones, sesquiterpenoids, and steroids and it contains about Hydroalcoholic extract of C. asiatica at a dose of 2 mg/mL 11.2% protein and rich in Ca and phosphorus.[32] A study given to 20-month-old female mice and tested on an open shows that 50% ethanolic extract of T. cordifolia has potent field and Morris water maze model which show potential anxiolytic property and also prevent anxiety induced learning for conferring clinical benefit in Alzheimer Disease and its and memory impairment.[33] Antinociceptive study was done neuroprotective properties.[42] Furthermore, in another study on Swiss albino mice using the model of acetic acid at a dose C. asiatica ethanolic extract was studied on male Sprague of 25 mg/kg which shows a great effect on it. It also shows Dawley rats at a dose of 100, 200, and 400 mg/kg, (p.o) and good anti-oxidant activity as the stock solution of the plant tested on open field, elevated plus maze, and hole board and extract (10 mg/ml) used which was prepared in ethanol and gives a positive result against anxiety.[43] its serial dilution used in the study.[34] Sankhpuspi (Convolvulus pluricaulis) is used as a brain tonic. Mandukparni (Centella asistica) aqueous extract was The whole herb of Shankhpushpi was used medicinally in the reported to have cognitive-enhancing as well as antioxidant form of a decoction with cumin and milk in fever, nervous effects in rats.[35] It increases pentobarbitone-induced debility, and loss of memory.[44] Research into the chemical sleeping time and decreases immobility in rats tested constituents in Shankhpushpi had found the presence in force swim model.[36] About 0.1% essential oils and carbohydrate-D-glucose, maltose, rhamnose, sucrose and other volatile constituents, C. asiatica contains a wide starch, and certain other biochemicals which include glacial range of other substances.[37] The most biologically active acetic acid, scopoletin, three coumarins, β-sitosterol, tropane compounds isolated from C. asiatica is the terpenes, for alkaloids, kaempferol, convoline, convolidine, convolvine, example, asiaticoside, madecassic acid, madecassoside, and confoline, convosine, palmitic acid (66.8%), linoleic acid asiatic acid. In another study, it was found that asiaticoside (2.3%), and straight chain hydrocarbon hexatriacontane, is possessing wound healing activity by enhancing the 20-oxodotriacontanol, tetratriacontanoic acid, and stimulation of levels of antioxidant.[38] C. asiatica is a very 29-oxodotriacontanol6.[45] Alcoholic extract of plant yield well-recognized drug, and it’s 3–4 fresh leaves with 1–2 kaempferol, Di-oh-cinnamic acid and β-stosterolglucos black pepper are given to children to reinforce the memory. steroid of microphyllic acid.[46-51] Ethyl acetate and aqueous This plant is used in nervous, blood, and skin diseases. The fractions of the ethanolic extract of aerial parts of C. pluricaulis plant has antiseptic property also diuretic and used in leprosy, showed significant anxiolytic effect. The ethyl acetate psoriasis, syphilitic ulcer, fever, dysentery, rheumatism, and fractions reduced the neuromuscular coordination indicative

Table 1: Plant ingredients of Ashtanga Ghrita [10] Name Rasa Latin name Part used Ratio Vacha Katu, Tikta A. calamus Linn Rhizome 1 Indulekha Kashay, tikta P. corylifolia Linn Seed 1 Mandukparni Tikta, kashay, C. asiatica (Linn) Urban Whole 1 Madhur plant Shankhpushpi Katu, Tikta C. pluricaulis Choisy Whole 1 plant Shatavari Madhur, Tikta A. racemosus Willd Root 1 Brahmasoma Kashay, Tikta A. speciosa Sweet Heartwood 1 Amruta Katu, Tikta T. cordifolia (Willd) Stem 1 Miers Brahmi Kashay, Tikta B. monnieri (Linn) Whole 1 Pennell plant A. calamus: Acorus calamus, C. pluricaulis: Convolvulus pluricaulis, A. racemosus: Asparagus racemosus, A. speciosa: Argyreia speciosa, T. cordifolia: Tinospora cordifolia, C. asiatica: Centella asiatica

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S53 Majumder and Gautam: A critical review on Ashtanga ghrita of the muscle relaxant activity at a higher dose.[52] Another chronic constriction injury-induced behavioral, biochemical study showed nootropic and anxiolytic activity of an aqueous and histopathological changes in rats. These effects may be methanolic extract of C. pluricaulis[53] Sankhpuspi is a plant attributed to its potential anti-oxidative, anti-inflammatory, use in Medhya, digestive, appetite stimulant, and carminative neuroprotective, and calcium inhibitory actions.[71] A. for the digestive system. It also has cardioprotective property calamus may help in stress as in studies. It’s been observed and control hypertension. It also a good remedy for chronic that rhizome extract of the plant was dosed to male rats as cough in Ayurveda.[46] This plant has also been reviewed 100 mg/kg and 200 mg/kg body weight orally for 21 days and and reported for its potent anxiolytic, neurodegenerative, the result show a great impact on the stress reduction with the and antistress activity by various researchers.[52-55] Alcoholic help of Elevated plus-maze and Hebb-Williams maze models extracts of Evolvulus Alsinoides and C. pluricaulis at and the data are also collected by tissue processing in which 250 mg/kg body weight given to rats by making a suspension the oxidant anti-oxidant systems were measured in brain.[72] with 2% tween 80 and that gives a good result on learning memory.[56] Vidhara (Argyreia speciosa Linn) belongs to family Convolvulaceae has been used in the different system of Shatavari (Asparagus racemosus) is use mostly in the traditional medication for the treatment of diseases and treatment of stomach ulcers, lung abscess, menopause, herpes, ailments of human beings.[73] Vidhara root has potent power and chronic fevers and as a form of health food ingredients to improve the memory. Studies show 100 and 200 mg/kg in Ayurvedic formulations[57] A. racemosus root extract has aqueous extract of root successfully reverse amnesia induced good significant antibacterial activity against S. aureus, by diazepam, in aged animals.[74] The alcoholic extract of Bacillus subtilis, Staphylococcus werneri, Pseudomonas the root exhibited statistically significant anti-inflammatory putida, Pseudomonas aeruginosa, and Proteus mirabilis.[58,59] activity against granuloma formation technique in albino A. racemosus is widely used in Ayurveda for its medicinal rats which comparable to acetylsalicylic acid.[75] The properties, and it’s anticancerous property has been implicated hydroalcoholic extract of A. speciosa roots was tested for in the regulation of cell proliferation and apoptotic gene the presence of carbohydrates, proteins, alkaloids, saponins, products. Change in the control of the cell death processes tannins, and essential oils using standard procedures.[76] such as apoptosis and autophagy may extend the lifespan of Aqueous extract A. speciosa Linn at a dose of 100 mg/kg and cells and favor neoplastic expansion.[60] The plant has property 200 mg/kg was studied on mice and tested in Elevated Plus- to the treatment of neurodegenerative disorders. In Ayurveda, Maze and Passive avoidance model, and the result show a Shatavari used as a rasayana herb and has been used as an great impact on learning memory.[77] adaptogen to increase the non-specific resistance of organisms against a variety of stresses.[61] A. racemosus has studied, and its ethanolic extract showed very potent activity against CONCLUSION Alzheimer’s Disease, as its dosed at 2.5 mg/kg body weight (b.w.) to albino rats and tested in Elevated Plus Maze and also Ashtanga Ghrita is a classic Medhya rasayan drug and the plant studied the passive avoidance test.[62] drug used in it also has nootropic effect individually. The plant drug used in the formulation has some other potent activity Vacha (Acorus calamus) belong to Araceae family is a herb individually such as Bakuchi, Brahmi, and Guduchi have which is basically semiaquatic, perennial, aromatic herb with antioxidant property. Whereas Bakuchi and Shatavari have its rhizome being horizontal, rounded, somewhat vertically antibacterial activity, etc. This type of individual information compressed, spongy and leaves grass like and sword-shaped; about the plant may help to modify the formulation or in the grown all over India.[63] Rhizome is a useful part having further study so the formulation or the modified form may be Medhya quality. It has been used in Indian and Chinese used in other diseases. Hence, studying the classical formulation system of medicine for hundreds of years to cure diseases and its ingredients individually may help in future for further especially the CNS abnormalities.[64-66] A. calamus has a study and development. The modern concept of medicine and beneficial effect on the learning, memory process in mentally new advanced technology may help in the modification and challenged children.[67] The API indicates the use of the dried the theory given here may help to succeed it. rhizomes as a brain tonic in weak memory, psychoneurosis, and epilepsy.[68] Vacha is a brain tonic which promotes higher mental functions. It is an ideal herb for mediators, students, REFERENCES and musicians and all who need deep focus and attention in their work. Vacha penetrates deep into the brain tissues and 1. Jenner P, Elliott PN, Clow A, Reavill C, Marsden CD. scrapes toxins from the subtle channels in mind and opens the A comparison of in vitro and in vivo dopamine receptor nadis of the higher chakras. Vacha heating qualities stimulate antagonism produced by substituted benzamide drugs. the brain and increase alertness and focus. 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Assessment Report on Centella asiatica (L.) Urban, Uterine disorders. Fitoterapia 1993;64:463-5. Herba, Based on Article 10a of Directive 2001/83/ 52. Nahata A, Patil UK, Dixit VK. Anxiolytic activity of EC as Amended, 25 November 2010 EMA/ evolvulusalsinoides and Convolvulus pluricaulis in HMPC/291177/2009 Committee on Herbal Medicinal rodents. Pharm Biol 2009;47:444-51. Products (HMPC); 2010. 53. Malik J, Karan M, Vasisht K. Nootropic, anxiolytic and 38. Shukla A, Rasik AM, Jain GK, Shankar R, Kulshrestha CNS-depressant studies on different plant sources of DK, Dhawan BN. In vitro and in vivo wound healing shankhpushpi. Pharm Biol 2011;49:1234-42. activity of asiaticoside isolated from Centella asiatica. 54. Naveen K, Suresh C, Kumar SS, Chandra TR. J Ethnopharmacol 1999;65:1-1. Comprehensive literature review of mandukparni 39. Tiwari S, Gehlot S, Gambhir IS. Centella asiatica: (Centella asiatica) Wsr to its medicinal properties. A concise drug review with probable clinical uses. 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Traditional Indian herbs Convolvulus Appl Biol Pharm 2011;2:312-4. pluricaulis and its medicinal importance. J Pharmacog 60. Verma SP, Tripathi VC, Das P. Asparagus racemosus leaf Phytochem 2012;1:1. extract inhibits growth of UOK 146 renal cell carcinoma 45. Mishra SN. Review on ethnomedicinal uses and cell line: Simultaneous oncogenic PRCCTFE3 fusion phytopharmacology of memory boosting herb transcript inhibition and apoptosis independent cell Convolvulus pluricaulis. Aust J Med Herb 2010; death. Asian Pac J Cancer Prev 2014;15:1937-41. 22:19-25. 61. Sharma A, Sharma V. A brief review of medicinal 46. Naveen K, Suresh C, Kumar SS, Chandra TR. properties of Asparagus racemosus (Shatavari). J Pure Morphological, controversial and literary review of Appl Biosci 2013;1:48-52. shankhpushpi. Int J Ayurveda Pharm Chem 2016;4:10. 62. Uddin SM, Mamun AA, Iqbal MA, Wahid F, Rony RK. 47. Rastogi R, Mehrotra B. Compendium of Indian Neuroprotective activity of Asparagus racemosus Linn. 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Medicinal Plants used in Ayurveda, Vol. 1. New Delhi, 71. Muthuraman A, Singh N. Attenuating effect of Acorus India: Central Council for Research in Ayurveda and calamus extract in chronic constriction injury induced Siddha; 2000. p. 469. neuropathic pain in rats: An evidence of anti-oxidative, 64. Lai XY, Liang H, Zhao YY. A survey of the studies on anti-inflammatory, neuroprotective and calcium inhibitory chemical constituents and pharmacological activities effects. BMC Complement Altern Med 2011;11:24. of Acorus plants. Zhongguo Zhong Yao ZaZhi 72. Reddy S, Rao G, Shetty B, Hn G. Effects of Acorus 2002;27:161-5. calamus rhizome extract on the neuromodulatory 65. Shukla PK, Khanna V, Ali M, Maurya R, Khan MY, system in restraint stress male rats. Turk Neurosurg Srimal RC. Neuroprotective effect of Acorus calamus 2015;25:425-31. against middle cerebral artery occlusion-induced 73. Modi AJ, Khadabadi SS, Deokate UA, Farooqui IA, ischaemia in rat. Hum Exp Toxicol 2006;5:187-94. Deore SL, Gangwani MR. Argyreia speciosa Linn. f.: 66. Koo BS, Park KS, Ha JH, Park JH, Lim JC, Lee DU. Phytochemistry, pharmacognosy and pharmacological Inhibitory effects of the fragrance inhalation of essential studies. J Pharmacog Phytother 2010;2:34-42. oil from Acorus gramineus on central nervous system. 74. Joseph A, Mathew S, Skaria BP, Sheeja EC. Medicinal Biol Pharm Bull 2003;26:978-82. uses and biological activities of Argyreia speciosa Sweet 67. Asha V, Kumar AA. Phytochemical investigations, (Hawaiian Baby Woodrose)-An overview. India J Nat extraction and thin layer chromatography of Acorus Prod Resour 2011;2:286-91. calamus Linn. Int J Res Stud Biosci 2015;3:18-22. 75. Srivastava MC, Kant V, Tewari JP. Antiinflammatory 68. Ministry of Health, Government of India. The Ayurvedic activity of roots of Argyreia speciosa (Sumandrashokha). Pharmacopoeia of India. Part I., Vol. I to IV, (API). Mediscope 1972;15:219-2. New Delhi: Ministry of Health, Government of India; 76. Kokate CK. Practical Pharmacognosy. 4th ed. New Delhi: 2004. Vallabh Prakashan; 1994. p. 107-9. 69. Sharma AK, Sanghamitra D, Nigamanand B. Vacha 77. Joshi H, Kaur N, Chauhan J. Evaluation of nootropic (Acorus calamus Linn.): A valuable medicinal plant. Int effect of Argyreia speciose in mice. J Health Sci J Ayurveda Pharm Chem 2015;2:8. 2007;53:382-8. 70. Sharma AK, Sanghamitra D, Nigamanand B. Vacha (Acorus calamus Linn.): A valuable medicinal plant. Int J Ayurveda Pharm Chem 2015;2:1-15. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S57 A review on current trends of ayurvedic medicinal plants having antidiabetic activity and renal disorders

Devendra Nath, Sandhya Singh, Rajesh Verma, Pankaj Maurya, Ravi Tripathi, Shreya Kumari Department of Pharmacy, Ashoka Institute of Technology and Management, Varanasi, Uttar Pradesh, India

Abstract

Ayurveda and other Indian literature mentioned the use of plants in treatment of various human ailments. In the

REVIEW ARTICLE REVIEW last few years, there has been an exponential growth in the field of herbal medicine and gaining popularity both in developing and developed countries because of their natural origin and less side effects. Diabetes mellitus is a chronic heterogeneous disorder affecting the β-cells of endocrinal pancreatic gland nearly 10% of the population worldwide also the number of those affected is increasing day-by-day. Plant showing lowering the elevated glucose level mainly belongs to the family Leguminosae, Lamiaceae, Liliaceae, Cucurbitaceae, Asteraceae, Moraceae, Rosaceae, and Araliaceae. The most active plants have been known to cure and control diabetes without causing any side effects such as Allium sativum, Gymnema sylvestre, Citrullus colocynthis, Trigonella foenum greacum, Momordica charantia, and Ficus bengalensis. Chronic kidney disease is progressive forms of renal disorders associated with reduced renal function having no well-known etiopathogenesis. The available treatment modalities in conventional system of medicine are still evolving but peritoneal and hemodialysis along with nutritional supplements and renal transplant is the final step. In this regard, Ayurveda provides leads through its holistic line of management by incorporating dietary and lifestyle invention and bio-balancing effects of Ayurvedic drugs.

Key words: Chronic kidney disease, glucose ayurveadic drugs, insulin, natural products, β-cells diabetes mellitus

INTRODUCTION medicine is increasing rapidly in developed countries. TM is sometimes also the only affordable source of health care, iabetes is usually a lifelong (chronic) especially for the world’s poorest patients.[8] Insulin is the disease, in which there are high levels most common type of medication used in type 1 diabetes of sugar in the blood.[1] Diabetes treatment. It is also used in type 2 diabetes treatment. It is D given by injection and comes in different types. mellitus is a metabolic disorder initially characterized by a glucose level loss homeostasis, due to fat and protein metabolism Types of Diabetes Mellitus disturbances of carbohydrate, resulting from defects in insulin production, secretion, insulin The World Health Organization (WHO) classification of [2] action. Complications in some of these organs diabetes introduced in 1980 and revised in 1985 was based [3] can lead to death. More than 347 million on clinical characteristics. The two most common types of [4] people are affected by diabetes worldwide. diabetes were insulin-dependent diabetes mellitus (IDDM) The prevalence of diabetes has risen from 2.5% or (type I) and non-insulin-dependent diabetes mellitus [5] to 6.5% in the last 14 years. Diabetes-related (NIDDM) or (type II). WHO classification also recognized deaths are more common in the low- and middle- malnutrition-related diabetes mellitus and gestational income countries where more than 78%deaths diabetes Malnutrition-related diabetes was omitted from the occur.[6] The World Health Organization projects that diabetes will be the 7th leading cause of Address for correspondence: death in 2030.[7] Traditional and alternative Devendra Nath, medicines have been used since ancient times. Department of Pharmacy, Ashoka Institute of Technology Yet the use of traditional medicine (TM) and Management, Varanasi, Uttar Pradesh, India. remains widespread in developing countries, E-mail: [email protected] while the use of complementary and alternative

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S58 Nath, et al.: A review on current trends of ayurvedic medicinal plants having antidiabetic activity and renal disorders new classification because its etiology is uncertain, and it is Gestational Diabetes Mellitus unclear whether it is a separate type of diabetes.[9,10] Gestational diabetes, blood glucose elevation during pregnancy, is a significant disorder of carbohydrate metabolism due to Type I Diabetes Mellitus hormonal changes during pregnancy, which can lead to elevated blood glucose in genetically predisposed individuals. It is more The Type- I diabetes is dependent. It is a result of cellular common among obese women and women with a family history mediated autoimmune destruction of the insulin-producing of diabetes. It usually resolves once the baby is born, however, and secreting β-cells of the pancreas, which results in an after pregnancy, 5–10% of women with gestational diabetes are absolute deficiency of insulin for the body. Patients are more found to have type II diabetes, and 20% –50% of women have prone to ketoacidosis. It usually occurs in children and young a chance of developing diabetes in the next 5–10 years.[9-11,28,29] adults, usually before 40 years of age, although disease onset Gestational diabetes is a form of diabetes consisting of high can occur at any age. The patient with type I diabetes must blood glucose levels during pregnancy and goes away after the rely on insulin medication for survival. It may account for baby is born. It develops toward the treating diabetes without 5–10 % of all diagnosed cases of diabetes.[11] Autoimmune, any complication or any side effects is a challenging problem genetic, and environmental factors are the major risk factors in the medical community.[30] The medicinal plants used on for type I diabetes.[11-14] antidiabetic treatments possess pancreatic β-cells regenerating, insulin-releasing activity, and also fight the problem of insulin resist adipose tissue, and inhibit the glucose absorption from Type II Diabetes Mellitus the intestine.[31] The Type- II diabetes is independent. Two key features in the pathogenesis of type II diabetes mellitus are a decreased Testing for Hypoglycemic Activity ability of insulin to stimulate glucose uptake in peripheral tissues, insulin resistance, and the inability of the pancreatic The discovery of the oral synthetic hypoglycemic was a major in β- cell to secrete insulin adequately, β cell failure. The major the treatment of diabetes. Act by augmenting insulin secretion, sites of insulin resistance in type 2 diabetes are the liver, and the biguanides only workin the presence of residual insulin. skeletal muscle, and adipose tissue.[15] Both defects, insulin resistance, and β-cell failure, are caused by a combination There are many plant extract with proven hypoglycemic activity jambul, Syzygium cumini; fenugreek, Trigonella of genetic and environmental factors. Environmental factors foenum-graecum, garlic, A. sativum; onion. No isolated such as lifestyle habits (i.e., physical inactivity and poor compound from these plants have yet been developed for dietary intake), obesity, and toxins may act as initiating clinical use which are dietary compound have been tested in factors or progression factors for type II diabetes.[9,11,16-18] human diabetics and found to be hypoglycemic.

Factors Precipitating Lactic Acidosis in Patients The oral sulphonylureas in clinical use are hypoglycemic normal with Type 2 Diabetes Mellitus (i.e., non-diabetic) animals, and successful screening programs have been carried out using normal rabbits and rats; however, • Cardiac failurε. nowadays diabetic animals are usually employed clinical • Myocardial infarction. testing in human non-insulin dependent diabetics involves • Hepatic failure. measurement blood glucose levels after administering the test • Any hypoxic state. extract, after overnight fasting or preloading with glucose. • Clinical dehydration. • Shock (especially septic shock). Measurement of the Blood Insulin Levels • Severe sepsis and hemodynamiχ instabilitψ. • Major surgery. It may be useful to determine whether there is a rise in circulating insulin levels after glucose loading, and during treatment with plant extract. The usual methods are radio- EPIDEMIOLOGY immunoassay and enzyme-linked immunosorbent assay, available as kits, for example, from Boehringer, Mannheim; The prevalence of GDM in India varied from 3.8 to 21% in Novo Biolabs, Copenhagen; Pharmacia, Brussels, and others, different parts of the country, depending on the geographical for examples, see “Treatment of Results” locations and diagnostic methods used. GDM has been found to be more prevalent in urban areas than in rural areas.[19-26] Clinical Testing in Human Subjects For a given population and ethnicity, the prevalence of GDM corresponds to the prevalence of (Impaired Glucose Tolerance, Human non-insulin dependent diabetic volunteers can in non-pregnant adult) within that given population.[27] be used to test non-toxic plant extracts. However, the two

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S59 Nath, et al.: A review on current trends of ayurvedic medicinal plants having antidiabetic activity and renal disorders examples as hown in “treatment of results” also demonstrate Breakfast- 1 cup special k, 1 banana, 2 Table spoon the different mechanisms, there is the true hypoglycemic unsweetened Greek yoghurt, 5 Almonds, (sliced) herbal tea effect of the opuntia ficus-indica extract and the blunted insulin release and post-prandial glycemic profiles resulting Snack- 1 Date, oatmeal, and walnut ball, ice water w/lemon from ingestion of guar gum, Cyamopsis tetragonolobus. In the Opuntia experiment, this was not the case since the Lunch-baked chicken breast, 1 cup steamed vegetables, ½ patient did not receive a glucose load before the plant extract. cup cooked brown rice

Snack-celery w/homemade low-fat hummus Testing for Hypoglycemic Activity Dinner- Grilled salmon, ½ cup quinoa, 1 cup steamed The discovery of the oral synthetic hypoglycemic was a vegetables, herbal tea major in the treatment of diabetes. Act by augmenting insulin secretion, and the biguanides only work in the presence of residual insulin. Symptoms of Diabetes

There are many plant extract with proven hypoglycemic activity jambul, S. cumini; fenugreek, Trigonella foenum- graecum, garlic, A. sativum; onion. No isolated compound from these plants has yet been developed for clinical use, which are dietary compound have been tested in human diabetics and found to be hypoglycemic.

The oral sulfonylureas in clinical use are hypoglycemic normal (i.e., non-diabetic) animals and successful screening programs have been carried out using normal rabbits and rats; however, nowadays, diabetic animals are usually employed clinical testing in human non-insulin dependent diabetics involves measurement blood glucose levels after administering the test extract, after overnight fasting or preloading with glucose. • Fatigue or severe weakness. Diagnosis of GDM with 100‑g mg/dl mmol/l • Abnormal thirst. oral glucose load • Irritability. Fasting 94 5.4 • Unexplained weight loss. 1‑h 181 10.0 • Increased hunger. 2‑h 154 8.5 • Recurrent infections. 3‑h 141 7.7 • Blurred vision. • Increased urination and nocturnal.

Diagnosis of GDM with 75‑g mg/dl mmol/l In normal individuals, the liver acts a storehouse of oral glucose load carbohydrates and releases glucose whenever the need Fasting 94 5.4 arises. The pancreas produces insulin, which circulates the 1‑h 181 10.0 case of prediabetic patients; the pancreas does not produce enough insulin leading to increased levels of sugar in the 2‑h 154 8.5 blood up to 100–125 mg/dl. Nowadays, dial the number of adults suffering from diabetes is expected to increase Blood sugar Fasting Just ate 3 h after in threefold from 19.4 million in 1995 to 57.2 million level chart eating in 2025.[32] The three main important cl and polyphagia Normal 80–100 170–200 120–140 (increased hunger).[33] Pre‑diabetic 101–125 190–230 200+ Diabetic 126+ 220–300 200+ Methodology

Meal plan -1200 calories The study aimed to recollect and record, the information on antidiabetic plants from the hyperglycemic condition. After waking up-hot water/half squeezed lemon In this review, we have collected about 180 plants which

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S60 Nath, et al.: A review on current trends of ayurvedic medicinal plants having antidiabetic activity and renal disorders are effective for the reduction of hyperglycemic condition. Adhatoda vasica The plants have about medicinal plants with antidiabetic The methanolic extract from the leaves of A. vasica Nees activity. (Acanthaceae) showed a sucrose inhibitory activity with sucrose as a substrate. Compounds vasicine and vasicinol

Important Medicinal Plants Explored as showed a high sucrose inhibitory activity, and the IC50 Anti-Diabetic [Table 1] values were 125 μM and 250 μM, respectively. Kinetic data revealed that the compounds vasicine and vascinol inhibited Acacia arabica sucrose-hydrolysing activity of rat intestinal α- glucosidase competitively with Ki values of 82 μM and 183 μM, Acacia Arabica (babul) is used as home remedy in Indian respectively. This is the first report on the mammalian system of medicine for reducing the complications of diabetes. α-glucosidase inhibition of A. vasica and the inhibitory effect It is found that this plant extract acts as an antidiabetic agent on sucrase by vasicine and vascinol from this herb species. by acting as secretagouge to release insulin. It induces These results suggest the use of the extract of A. vasica as hypoglycemia in control rats but not in alloxanized animals. an antidiabetic agent and also show the possibility that Powdered seeds of Acacia arabica when administered the compounds, vasicine, and vascinol could be a useful (2, 3, and 4 g/kg body weight) to normal rabbits, induced treatment for metabolic disorders.[36] hypoglycemic effect by initiating release of insulin from pancreatic beta cells.[34] Aegle marmelos Adansonia digitata A. marmelos leaf extract is being used in Indian system of medicine as an antidiabetic agent. A methanolic extract of Leaves bark and fruits of A. digitata are traditionally A. marmelos was found to reduce blood sugar in alloxan- employed in several African regions as food, and for induced diabetic rats. Reduction in blood sugar could be seen medicinal purposes, and for the letter use, it is also named from 6th day after continuous administration of the extract and “the small pharmacy or chemist tree.[35] Hypoglycemic on 12th day sugar levels were found to be reduced by 54%. activity of methanolic stem bark extract of A. digitata in This result indicates that A. marmelos extract effectively Wister rats has been investigated in streptozotocin-induced reduced the blood glucose in diabetes induced by alloxan and diabetes. Treatment of streptozotocin-induced diabetic it also showed antioxidant activity.[37] Wister rats with the extract caused a significant reduction in the blood glucose levels when compared with control. The dose of 100 mg/kg showed a significant decrease Aloe Barbadensis after 1, 3, 5 and 7 h of extract administration, compared to control normal saline. In addition, the dose of 200 mg/kg Aloe, a popular houseplant, has a long history as a shown a significant decreased after 3, 5, and 7 h of extract multipurpose folk remedy. The plant can be separated into administration. The dose of 400 mg/kg also showed a two basic products: gel and latex. Aloe vera gel is the leaf significant decrease of blood glucose after 5 and 7 h of pulp or mucilage, Aloe latex, commonly referred to as extract administration, compared to control normal saline. “aloe juice,” is a bitter yellow exudate from the pericyclic These results suggest that the methanolic stem bark of tubules just beneath the outer skin of the leaves. Extracts A. digitata possesses antidiabetic effect on streptozotocin- of aloe gum effectively increase glucose tolerance in both [38] induced diabetic Wistar rats [35]. normaland diabetic rats. Treatment with prolonged but

Table 1: Medicinal plants having antidiabetic activity Plant activity Family Parts used Type of extract Alangium lamarckii Alangiaceae Leaves Alcoholic Albizia odoratissima Antidiabetic Mimosaceae Bark Methanol Axonopus compressus Antidiabetic Poaceae Leaves Methanol Berberis vulgaris Hypoglycemic Berberidaceae Root Aqueous Brassica juncea Hypoglycemic Cruciferae Seed Aqueous Caesalpinia digyna Antidiabetic Fabaceae Root Methanol Catharanthus roseus Hypoglycemic Apocynaceae Leaf Methanol Centaurium erythrea Antidiabetic Gentianaceae Leaf Aqueous Chaenomeles sinensis Rosaceae Fruits ethyl acetate Antidiabetic Costus speciosus Costaceae rhizome Hexane Antidiabetic A. compressus: Axonopus compressus, C. erythrea: Centaurium erythrea, C. sinensis: Chaenomeles sinensis

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S61 Nath, et al.: A review on current trends of ayurvedic medicinal plants having antidiabetic activity and renal disorders not single dose of exudates of aloe barbadensis leaves Azadirachta indica showed hypoglycemic effect in alloxanized diabetic rats. Single as well as prolonged dose of bitter principle of the Hydroalcoholic extracts of this plant showed same plant also showed hypoglycemic effect in diabetic antihyperglycemic activity in streptozotocin-treated rats. The rats. This action of A. vera and its bitter principle is through extract caused an increase in glucose uptake and glycogen stimulation of synthesis and/or release of insulin from deposition in isolated rat hemi diaphragm. Apart from pancreatic beta cells.[39] having antidiabetic activity, this plant also has antibacterial, antimalarial, antifertility, hepatoprotective and antioxidant effects.[42] Andrographis Paniculata

The chloroform extract of A. paniculata roots has been tested Boerhavia Diffusa for its antihyperglycemic activity in alloxan-induced diabetic rats using chronic and acute studies. Significant reductions in B. diffusa (Nyctaginaceae) is known as punarnava and is blood glucose levels were observed in both acute and chronic used as diuretic, hepatoprotective and for treatment of other studies. The extract significanly inhibited the induction of diseases in the Indian medicinal system. A study was designed albuminuria, proteinemia, and uremia. Activity with the to investigate the effects of daily oral administration of aqueous chloroform extract of A. paniculata roots and supports the solution of B. diffusa leaf extract (BLEt) (200 mg/kg) for traditional usage of the plant by Ayurvedic physicians for the 4 weeks on blood glucose concentration and hepatic enzymes control of diabetes.[40] in normal rats and alloxan-induced diabetic rats. A significant decrease in blood glucose and significant increase in plasma insulin levels were observed in the normal and diabetic rats Anthocephalus Indicus treated with BLEt. An oral glucose tolerance test was also performed in the same groups, and there was a significant A. indicus (family, Rubiacae: Hindi name- Kadam) is one improvement in glucose tolerance in rats treated with BLEt. such Ayurvedic remedy that has been mentioned in many A comparison was made between the action of BLEt and ancient Indian medical literatures to possess antidiarrheal, antidiabetic drug - glibenclamide (600 μg/kg). The effect of detoxification, analgesic, and aphrodisiac properties. A study BLEt was more prominent when compared to glibenclamide, was carried out to evaluate the hypoglycemic, lipid lowering, suggesting it was a more potent antidaibetic agent.[43] and antioxidant activities in root extract of A. indicus in alloxan-induced diabetic rats. Oral administration of ethanol Butea Monosperma extract of root (500 mg/kg body weight) for 21 days resulted in significant decrease in the levels of blood glucose, The plant B. monosperma belongs to the family Fabaceae. triglycerides, total cholesterol, phospholipid and free fatty It is also known as Butea frondosa, (Hindi- Dhak, Palas) acids. Furthermore, the root extract (100–400 μg/kg) inhibited and is found throughout India. A methanol extract of the generation of superoxide anions and hydroxyl radicals, in B. monosperma seeds, tested in vitro showed a significant both enzymic and non-enzymic systems, in vitro. The result anthelmintic activity, anticonvulsive, and hepatoprotective. of this study demonstrated hypoglycemic, lipid-lowering, In light of the traditional claim on the use of B. monosperma and antioxidant activities in root extract of A. indices, which in the treatment of diabetes, investigations were carried could help in the prevention of diabetic dyslipidemia and out to evaluate the effects of extract from the bark of [40] related diseases. B. monosperma on normal mice and alloxan-induced diabetic mice. The studies indicated that the crude aqueous Artanema Sesamoides extract exhibited statistically significant hypoglycemic and anti-hyperglycemic activities in normal and alloxan-induced [44] The methanolic extract of A. sesamoides was investigated diabetic albino rats, respectively. for its antidiabetic activity in streptozotocin-induced diabetic rat models. Administration of this extract Caesalpinia Bonducella significantly reduced the fasting blood glucose level and increased the glycogen level in liver, compared to a control C. bonducella F. (Leguminosae) is a medicinal plant, widely group. The extract also diminished the elevated level of distributed throughout India, and the tropical regions of the serum glutamic pyruvic transaminase, serum glutamic world. Four extracts (petroleum ether, ether, ethyl acetate, oxaloactetic transaminase, and serum alkaline phosphatase and aqueous) of the seed kernels were prepared and tested and also exhibited anti-oxidant activity. This study for their hypoglycemic potentials in normal rats as well as indicates the antidiabetic potential of Artanema sesamoides alloxan-induced diabetic rats. In diabetic rats, both polar and provides the basis for further research to isolate and to extracts (ethyl acetate and aqueous) similar to glibenclamide, identify the active constituents responsible for the reported showed significant hypoglycemic effect, besides, reversing activities.[41] the diabetes induced changes in lipid and liver glycogen levels.

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As far as the non-polar extracts were concerned, it was only long-term form of kidney disease and is differentiated from the ether extract that showed a marginal antidiabetic activity. acute kidney disease in that the reduction in kidney function Since both polar extracts were, through phytochemical must be present for over 3 months. It is an internationally analysis, found to contain triterpenoid glycosides, it can be recognized public health problem affecting 5%–10% of world presumed that they might be the active principles contributing population.[47] CKD is identified by blood test for creatinine, to the antidiabetic actions.[45] which is a breakdown product of muscle metabolism. Higher level of creatinine indicate a lower glomerular filtration rate and as a result a decreased capability of the kidneys to Cassia Auriculata excrete waste products. The modern management of CKD is C. auriculata (Family: Cesalpinaceae) is a common plant not satisfactory, and the ultimate goal is renal transplant. It in Asia, profoundly used in Ayurvedic medicine as a tonic, seeks attention from nephrologists and researchers to find out astringent, and as a remedy for diabetes, conjunctivitis, and suitable remedial measure from other alternative resources, ophthalmia. It is one of the principal constituents of ‘‘Avaarai Ayurveda is one of them. The management diseases in panchaga chooranam”- an Indian herbal formulation used Ayurveda are based on its totalistic effect of drugs and in the treatment of diabetes to control the blood sugar level. measures with minimal unwanted and side effects. Ayurveda The antidiabetic activity of aqueous extract of C. auriculata proclaims that naming of diseases is not necessary, but the flowers has been documented previously. Therefore, in a mainstay is to assess the Dosha, dushya, adhishthana along study, the antidiabetic potential of aqueous and ethanolic with strength of disease and patient, then incorporate the extracts of C. auriculata was assessed in alloxan-induced appropriate therapeutic interventions. The disease CKD is not diabetic rats. Both extracts gave significant reduction in blood fairly known in Ayurveda, but on the basis of pathogenetic glucose level because of presence of antidiabetic compounds events we can assess and plan the management. In this regard, such as flavonoids and phenolic acids. The antidiabetic we share our clinical experience of a 60 years old female who potential of ethanolic extract was more than that of aqueous was suffering from CKD since last 10 months. extract. The typical dose was found to be 0.25–0.5 g per kg body weight.[46] CKD, The global burden of noncommunicable diseases is of grave concern and has recently been highlighted by the WHO and a plethora of publications in prominent journals.[48-50] Medications for Type 1 Diabetes CKD has often been indicated as a major contributing factor to this burden, especially in low- and middle-income Insulin lispro (Humalog), Insulin aspart (NovoLog), Insulin countries.[51] Initial figures stated that CKD was present in glulisine (Apidra). 10% of the world’s population. Recently, this figure has risen to 14% in the USA, and by 2030, 27% of North Americans [51] Medications for Type 2 Diabetes >30 years of age are predicted to have CKD. An added burden to the recent number of people with CKD >45 years Sulfonylureas, Glimepiride (Amaryl), Glipizide (Glucotrol), old will be markedly increased, taking into consideration that Glyburide (DiaBeta, Micronase, Glynase). the estimated glomerular filtration rate (eGFR) decreases by 0.75–1.00 mL/min and, for example, 50% of UK children The older sulfonylureas are as follows: Acetohexamide. born in 2007 will live to the age of 103 years.[52] Chlorpropamide (Diabinese), Tolazamide (Tolinase), Tolbutamide (Orinase). ADVANCES IN IDENTIFYING FACTORS Chronic kidney disease (CKD) is progressive loss in renal THAT PREDICT DEVELOPMENT OF CKD function over a period of months or years. It is also called AND ITS PROGRESSION as chronic kidney failure. Signs and symptoms of kidney disease are often nonspecific, meaning they can also be caused by some other illnesses because kidneys are highly Hypertension adaptable organ in the body and able to compensate for its lost function. The signs and symptoms may appear at the stage Hypertension is one of the modifiable comorbid variables of irreversible damage, which includes nausea, vomiting, that should be evaluated and managed properly in loss of appetite, fatigue and weakness, sleep problems, children with CKD. An increase in BP causes increase changes in urine output, decreased mental sharpness, muscle intraglomerular pressure and hyperfiltration that leads to twitches and cramps, hiccups, swelling of feet and ankles, progressive deterioration of renal function.[53] The CKiD persistent itching, shortness of breath, high blood pressure study has shown that as high as 64% of pediatric CKD (BP) (hypertension) etc.[47] Often, it is diagnosed as a patients required antihypertensive medications to control result of screening of people known to be at risk of kidney their BP.[54] Furthermore, comparing between the patients problems, such as those with high BP or diabetes and those with uncontrolled BP and controlled BP, uncontrolled group with a blood relative with renal disorders. It is considered as used significantly less renin-angiotensin antagonists than the

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S63 Nath, et al.: A review on current trends of ayurvedic medicinal plants having antidiabetic activity and renal disorders controlled group. Some pediatric CKD patients may have CKD.[57] The nature of cardiovascular death in children normal BP in the clinic but they have elevated BP over the is different than that in adults. In adults, coronary artery period of 24 h. disease and congestive heart failure are the leading causes, while in children, cardiomyopathy and arrhythmia are The optimal target of BP in pediatric CKD patient has also most prevalent.[58] Recently, the CKiD study found that been studied in the randomized control study “Effect of pediatric CKD patients with HT also had decreased heart strict BP control and ACE inhibition on progression of CKD rate variability and increased BP variability. Both findings in pediatric patients” also known as “ESCAPE trial”.[55] It are signs of sympathetic nervous system over-activity.[59] has shown that intensified BP control showed a substantial Dyslipidemia is also a known risk factor of cardiovascular benefit on slowing CKD progression in pediatric patients disease. Saland et al.[60] have shown that 45% of pediatric [Tables 2 and 3]. CKD patients had dyslipidemia.

Cardiovascular Disease CKD-Mineral and Bone Disorder (MBD)

Children with CKD are at an increased risk to develop CKD causes disordered regulation of mineral metabolism cardiovascular disease.[56] Parekh et al.[42] has shown that with subsequent alterations in skeletal and cardiovascular pediatric patient with CKD who were on dialysis had cardiac biology which is now referred to as CKD-MBD.[61] death rate as high as 20 per 1,000 patient-year. Increase Hyperparathyroidism in advanced CKD is secondary to the in sympathetic activity has been associated with increase deficiency of 1, 25 -dihydroxy vitamin D (1,25 (OH)2D) in cardiovascular risk as shown in the adult patient with combined with hyperphosphatemia leading to abnormal bone turnover and mineralization. Fibroblast growth factor 23 (FGF23) is a bone-derived circulating hormone that Table 2: Clinical stages of CKD inhibits renal phosphate reabsorption and suppresses the Stage Glomerular filtration Comments synthesis of 1,25 (OH)2D thereby acting as a phosphaturic rate (mL/min) hormone. Circulating FGF23 was significantly elevated in CKD 1 90–110 Normal function patients with CKD and its concentration correlated with [62] CKD 2 60–89 Asymptomatic renal creatinine clearance. FGF23 normalizes serum phosphate and decreases 1,25 (OH)2D levels in early stage CKD 3a 45–59 Subclinical symptoms CKD, and suggests a pathological sequence of events for the development of secondary hyperparathyroidism triggered by CKD 3b 30–44 Mild clinical increased FGF23, followed by a reduction of 1,25 (OH)2D symptoms and calcium levels, thereby increasing parathyroid hormone CKD 4 15–29 Moderate‑to‑ severe secretion.[63] Portale et al.[64] found that serum FGF23 is the symptoms earliest detectable abnormality in mineral metabolism, and CKD 5 <15 At or nearly at levels are highest in glomerular diseases. Serum phosphorus CKD: Chronic kidney disease levels, adjusted for age, were significantly lower at GFR of 60–69 ml/min per 1.73 m2 than higher GFR, but thereafter they became higher in parallel with FGF23 as GFR Table 3: Recent advances in slowing the declined.[63] progression of CKD Modality Method and mode of functional Recent studies have shown that the induction of vascular stabilization calcification begins in early normophosphatemic CKD Type 2 diabetes Safety data on the use of MF in by the reduction of vascular Klotho and increased diabetes in CKD stages FGF23 secretion.[65] Studies of the vasculature in CKD ADPKD Slowing CKD with statin therapy indicate the presence of osteoblastic differentiation in the Acidosis Early treatment of mild acidosis vessel wall suggesting that uremic serum and high phosphate using bicarbonate (oral) stimulate osteoblastic differentiation of calcifying vascular cells and vascular smooth muscle cells.[66] Gut metabolites TMAO in CKD reduced by red meat avoidance from CKD stage 3b onward International Society for Peritoneal Dialysis (ISPD) Uric acid Allopurinol to slow down progression from CKD stage 3b onward ISPD is an International society aimed to advanceknowledge Exercise From CKD stage 3 onward of peritoneal dialysis and to promote advancement of such CKD: Chronic kidney disease, MF: Metformin, ADPKD: knowledge through scientific meetingsand publications. In Autosomal‑ polycystic kidney disease, TMAO: Trimethylamine 2012, ISPD developed practice guideline for the management N‑oxide of peritonitis in pediatric patients with peritoneal dialysis.[67]

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Diet DISCUSSION

Patient was advised to restrict salty, fried, spicy, heavy, The body cannot produce enough insulin, in which the and oily food items. She was restricted for fluid intake and diabetes is a chronic disease that occurs when or cannot use take fluid as per 24 h urine output and protein rich diet. The insulin effectively.[68] The diabetes disease by the year 2025, treatment response was assessed on the basis of clinical it is projected that 300 million people will have diabetes symptomatology after a course of medicines for 15 days patient.[69] and it may reach to 366 million diabetes patient in and significant improvement was found in the associated the year 2030.[70] Type 2 diabetes is a common condition and symptoms. The patient was then discharged and advised to a serious global health problem. In most countries, diabetes continue the following medicine for 15 days and asked to has increased alongside rapid cultural and social changes: report. ageing populations, increasing urbanisation, dietary changes, reduced physical activity, and unhealthy behaviors.[71] A In first follow-up (after 15 days) it was found that patient got person’s risk of developing Type 2 diabetes mellitus has been 50% improvement. The improvement in term of the patient’s shown to be highly linked to obesity and any family history [72] view in clinical symptoms was as follows: of diabetes. The hyperglycemic condition causes increased • Reduction in breathlessness. glycosylation leading to biochemical and morphological • Reduction in facial and pedal edema. abnormalities due to altered protein structure and develop the [73] • Improvement in desire of intake of food. neuropathy, retinopathy, neuropathy, and cardiomyopathy. In 2005, Diabetes patient kills 1.1 million and more than 220 • Improvement in bowel function. million people worldwide have diabetes mellitus. • Improvement in weakness. It would be right to say that modern system of medicine is Relevant investigations capable of offering reasonably effective treatment for so many diseases. The diagnostic tools to find out disease- CBC: Hb-8.0g/dl RFT: Na+ -135.2meq/l causing factors are also equally good. However, here, in this case, neither the investigations nor the treatment helped much TC-7030/μl K+ -4.1meq/l for considerable period. The patient was not satisfied by modern management. In this case, we observed that the given DC- N68, L22, E4, M 6 Cl- -108.1meq/l Ayurvedic drugs were significantly reduced the blood urea, sr. creatinine level and improved the hemoglobin level. This RBC: 257000/μl Sr. Creat-5.8 mg/dl is probably due to renoprotective and nephrogenetic effect of Punarnawa,[3-7] which is the major part of current Ayurvedic HCT: 24.4% Sr. Cal: 10.4 mg/dl prescription. The hemoglobin level was also improved from 7.5 g/dl to 9.2 g/dl, without any conventional hemetinic drugs MCV: 94.0fl Blood urea- 202 mg/dl and blood transfusion because of using Tablet Abhralauha and punarnava mandoor which provides sufficient nutrition MCH: 31.0pg Phosphate-3.7mg/dl at the level of Saptadhatus and helps in the blood formation by directly or indirectly. After thorough interrogation and physical and systemic examination the following medicines advised for another 15 days: CONCLUSION

Treatment advised: Gokshuradi gugglu (125 mg)-2 Among many disease or disorders of carbohydrate, fat and BD, Punarnawastaka kwath -40 ml BD, Prawal pishti protein metabolism, diabetes is a serious disorder effecting (125 mg) -1TDS, Punarnawa mandoor (500 mg) 1TDS & large population of the world. It is associated with decreased Haritaki Churna- 1tsf/HS with warm water. insulin production or resistance toward its action. Plants have been traditionally used to treat diabetes patients, both insulin dependent and non insulin dependent diabetes. They Drug Sources have also been reported to be used in associated conditions of diabetes such as diabetic peripheral neuropathy, diabetic 1. Punarnavastaka kwath (Bhaishajyaratnawali). retinopathy. Recent scientifically carried out research 2. Punarnava mandoor (Bhaishajyaratnawali). work has justified the role of herbs in the management of 3. Praval pishti tab (Dhutapapeswara). diabetes, however, it would be unwarranted to assure that 4. Green punarnava syrup (Dhanwantri pharmaceuticals). all these plants can be blindly used in diabetic patients. 5. Gokshuradi gugglu (Bhaishajyaratnawali). Authors feel that still there these plants have to go a long 6. Haritaki Churna (Bhaishajyaratnawali). way in terms assessment parameters such as toxic effects,

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S65 Nath, et al.: A review on current trends of ayurvedic medicinal plants having antidiabetic activity and renal disorders herb-herb; herb-drug interaction and ongoing exploration 12. Abebe D, Debella A, Urga K. Illustrative Checklist: regarding pharmacological actions and isolation of bioactive Medicinal Plants and Other Useful Plants of Ethiopia. compounds should be continued. Although there is an increase Nairobi, Kenya: Camerapix Publisher International, in the number of patients suffering from diabetes in every age EHNRI; 2003. p. 188-94. group during the last decade. Herbs are highly esteemed for 13. Cavallerano JO, Cooppan R. Optometric clinical practice millennia as a rich source of therapeutic agents for prevention guideline care of the patient with diabetes mellitus. and treatment of diabetes and its ailments. Although the 3rd ed. U.S.A, Lindbergh Blvd., St. Louis, MO: American contribution of modern synthetic medicine for elevating the Optometric Association 243 N; 2002. p. 63141-7881. human sufferings cannot be underestimated, equally true is 14. Trachtenbarg DE. Diabetic ketoacidosis. Am Fam the fact that most of them leave unwanted harmful side/toxic Physician 2005;71:1705-14. effects on the human system disturbing the basic physiology? 15. Ostenson CG. The pathophysiology of Type 2 During the last three decades or so, there has been serious diabetes mellitus: An overview. Acta Physiol Scand realization of these problems associated with synthetic drugs 2001;171:241-7. and as a result the world has started looking towards the herbs 16. Lindstrom J, Eriksson JG, Valle TT, Aunola S, Cepaitis Z, as agents of therapy which, apart from being comparatively Hakumaki M, et al. Preventionof diabetes mellitus in economical and easily available, are relatively free from the subjects with impaired glucose tolerance in the Finnish problems of side effects, toxicity, and developing resistance diabetes prevention study: Results from a randomized toward causative organisms. clinical trial. J Am Soc Nephrol 2003;14:S108-13. 17. Uusitupa M. Lifestyles matter in the prevention of Type 2 diabetes. Diabetes Care 2002;25:1650-1. REFERENCES 18. Li WL, Zheng HC, Bukuru J, Kimpe ND. Natural medicines used in the traditional Chinese medical system 1. Waugh A, Grant A. Ross and Wilson Anatomy and for therapy of diabetes mellitus. J Ethnopharmacol Physiology and Illness. 12th ed. UK: Elsevier Health 2004;92:1-21. Sciences; 2014. p. 236-8. 19. Seshiah V, Balaji V, Balaji MS, Selvam AP, Kapur A. 2. Barcelo A, Rajpathak S. Incidence and prevalence of Pregnancy and diabetes scenario around the World: diabetes mellitus in the Americas. Am J Public Health India. Int J Gynaecol Obstet 2009;104 suppl 1:S35-8. 2001;10:300-8. 20. Seshiah V, Balaji V, Balaji MS, Selvam AP, Arthi T, 3. Par L, Saravanan R. Antidiabetic effect of diasulin, an Thamizharasi M, et al. Prevalence of GDM in South herbal drug, on blood glucose, plasma insulin and hepatic India (Tamil Nadu)-A community based study. J Assoc enzymes of glucose metabolism in hyperglycaemic rats. Physicians India 2008;56:329-33. Diabetes Obesity Metab 2004;6:286-92. 21. Zargar AH, Sheikh MI, Bashir MI, Masoodi SR, 4. Danaei G, Finucane MM, Lu Y, Singh GM, Cowan MJ, Laway BA, Wani AI, et al. Prevalence of gestational Paciorek CJ, et al. National, regional, and global trends diabetes mellitus in Kashmiri women from the Indian in fasting plasma glucose and diabetes prevalence since subcontinent. Diabetes Res Clin Pract 2004;66:139-45. 1980: Systematic analysis of health examination surveys 22. Grewal E, Kansra S, Khadgawat R, Kachhawa G, and epidemiological studies with 370 country-years and Ammini AC, Kriplani A, et al. Prevalence of GDM 2·7 million participants. Lancet 2011;378:31-40. Among Women Attending a Tertiary Care Hospital 5. Anonymous. Diabetes Atlas. 3rd ed. Brussels: AIIMS Presented at DIPSI 2009 and 5th DIP Symposium. International Diabetes Federation; 2006. Sorrento, Italy; 2009. 6. Mathers CD, Loncar D. Projections of global mortality 23. Singh ID, Devi B, Devi I, Singh P. Scientific Presentation and burden of disease from 2002 to 2030. PLoS Med Volume of the First National Conference of the DIPSI. 2006;3:e442. Chennai; 2006. 7. World Health Organization. Global Status Report on 24. Yuvaraj MG. Data Presented at the First National Non Communicable Diseases 2010. Geneva: WHO; Conference of DIPSI. Chennai; 2006. 2011. p. 7-176. 25. Swami SR, Mehetre R, Shivane V, Bandgar TR, 8. World Health Organization. Traditional Medicine Menon PS, Shah NS. Prevalence of Carbohydrate Strategy. Geneva: WHO; 2002-2005. p. 1-3. intolerance of varying degrees in pregnant females in 9. Holt RI. Diagnosis, epidemiology and pathogenesis Western India (Maharashtra)-A hospital-based study. of diabetes mellitus: An update for psychiatrists. Br J J Indian Med Assoc 2008;106:712-4. Psychiatry 2004;184:s55-63. 26. Divakar H, Tyagi S, Hosmani P, Manyonda IT. Diagnostic 10. Tiwari AK, Rao JM. Diabetes mellitus and multiple criteria influence prevalence rate for gestational diabetes: therapeutic approaches of phytochemicals: Present Implications for interventions in an Indian pregnant status and future prospects. Curr Sci 2002;83:30-8. population. Perinatology 2008;10:155-61. 11. National Diabetes Fact Sheet (NDFS). United States; 27. Yogev Y, Ben-Haroush A, Hod M. Pathogenesis of 2005. Available from: http://www.cdc.gov/diabetes/pubs/ gestational diabetes mellitus. In: Hod M, Jovanovic L, Di pdf/ndfs_2005.pdf. [Last accessed on 2009 Nov 10]. 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Diabetes and Pregnancy. 1st ed. London: Martin Dunitz, diffusa L. effect on hepatic key enzymes in experimental Taylor & Francis Group plc; 2003. p. 46. diabetes. J Ethnopharmacol 2004;91:109-13. 28. Worthley LI. The Australian Short Course on Intensive 44. Deore SL, Khadabadi SS, Daulatkar VD, Deokate UA, Care Medicine. South Australia: Handbook, Gillingham Farooqui IU. Evaluation of hypoglycemic and Printers; 2003. p. 31-55. antidiabetic activity of bark of Butea monosperma. 29. Conn EE, Stumph PK. Outline of Biochemistry. Pharm Mag 2008;4:134-8. New York: 5th ed. John Wiley & Sons;1987. 45. Parameshwar S, Srinivasan KK, Rao CM. Oral 30. Maruthupandian A, Mohan VR, Kottaimuthu R. antidiabetic activities of different extracts of Caesalpinia Ethnomedicinal plants used for the treatment of diabetes bonducella seed kernels. Pharm Biol 2002;40:590-5. and jaundice by Palliyar tribals in Sirumalai hills, 46. Hakkim FL, Girija S, Kumar RS, Jalaludeen MD. Effect Western G; 2011. of aqueous and ethanol extracts of Cassia auriculata L. 31. Kavishankar GB, Lakshmidevi N, Mahadeva MS, flowers on diabetes using alloxan induced diabetic rats. Prakash HS, Niranjana SR. Diabetesand medicinal Int J Diabetes Metab 2007;15:100-6. plants-A review. Int J Pharm Biomed Sci 2011;2:65-80. 47. Longo D, Fauci A, Kasper D, Hauser S, Jameson J, 32. Jayaprasad B, Thamayandhi D, Sharavanan PS. Loscalzo J. Harrison’s Principles of Internal Medicine. Traditionally using antidiabetic medicinal plants in Chronic Kidney Disease. 18th ed., Vol. 02. New York, Tamil Nadu. Int J Res Pharm 2011;2:18. NY: Mcgraw-Hill; 2012. p. 2310-7. 33. Kumar A, Illavarasan R, Jayachandran T, Deecaraman M, 48. Jha V, Garcia-Garcia G, Iseki K, Li Z, Naicker S, Aravindan P, Padmanabhan N, Krishnan MR. Anti- Plattner B, et al. Chronic kidney disease: Global diabetic activity of Syzygium cumini and its isolated dimension and perspectives. Lancet 2013;382:260-72. compound against Streptozotocin-Induced diabetic rats. 49. Couser WG, Remuzzi G, Mendis S, Tonelli M. The 34. Wadood A, Wadood N, Shah SA. Effects of Acacia arabica contribution of chronic kidney disease to the global and Carallum edulis on blood sugar levels of normal and burden of major noncommunicable diseases. Kidney Int alloxan diabetic rabbits. J Pak Med Assoc 1989;39:208-12. 2011;80:1258-70. 35. Tanko Y, Yerima M, Mahdi MA, Yaro AH, Musa KY, 50. World Health Organization. Preventing Chronic Mohammed A. Hypoglycemic activity of methanolic Diseases: A Vital Investment. Geneva: WHO; 2005. stem bark of Adansonnia digitata extract on blood 51. Hoerger TJ, Simpson SA, Yarno BO, Pavkov ME, glucose levels of streptozocin-induced diabetic wistar Burrows NR, Saydah SH, et al. The future burden of rats Int J Appl Res Nat Prod 2008;1:32-6. CKD in the United States: A simulation model for the 36. Gao H, Huang YN, Gao B, Li P, Inagaki C, Kawabata J. CDC CKD Initiative. Am J Kidney Dis 2015;65:403-11. Inhibitory effect on α- glucosidase by Adhatoda vasica 52. Select Committee on Public Service and Demographic Nees. Food Chem 2000;108:965-72. Change, House of Lords, London, UK. Ready for 37. Sabu MC, Ramadasan K. Antidiabetic activity of Aegle ageing? 2013. Available from: http://www.publications. marmelos and its relationship with its antioxidant parliament.uk/pa/ld201213/ldselect/ldpublic/140/14003. properties. Indian J Physiol Pharmacol 2001;48:81-8. htm. [Last accessed on 2017 Apr04]. 38. Awadi FM, Gumaa KA. Study on the activity of the 53. Schaefer B, Wuhl E. Educational paper: Progression in individual plants of an antidiabetic mixture. Acta chronic kidney disease and prevention strategies. Eur J Diabetol Lat 1987;24:37-41. Pediatr 2012;171:1579-88. 39. Ajabnoor MA. Effect of aloes on blood glucose level 54. Flynn JT, Mitsnefes M, Pierce C, Cole SR, Parekh RS, in normal and alloxan diabetic mice. J Ethnopharmacol Furth SL, et al. Blood pressure in children with chronic 1990;8:215-20. kidney disease: A report from the chronic kidney disease 40. Kumar V, Khanna AK, Khan MM, Singh R, Singh S, in Children study. Hypertension 2008;52:631-7. Chander R, et al. Hypoglycemic, lipid lowering and 55. Wuhl E, Trivelli A, Picca S, ESCAPE Trial Group, antioxidant activities in root extract of Anthocephalus Litwin M, Peco-Antic A. Strict blood-pressure control indicus in alloxan induced diabetic rats. Indian J Clin and progression of renal failure in children. N Engl J Biochem 2009;24:65-9. Med 2009;361:1639-50. 41. Selvan VT, Manikandan L, Kumar GP, Suresh R, 56. Muscheites J, Meyer AA, Drueckler E, Wigger M, Kakoti BB, Gomathi P, et al. Antidiabetic and antioxidant Fischer DC, Kundt G, et al. Assessment of the effect of methanol extract of Artanema sesamoides in cardiovascular system in pediatric chronic kidney Streptozotocin-induced Diabetic rats. Int J Appl Res Nat disease: A pilot study. Pediatr Nephrol 2008;23:2233-9. Prod 2008;1:25-33. 57. Converse RL, Toto RD, Jost CM, Jacobsen TN, 42. Chattopadhyay RR, Chattopadhyay RN, Nandy AK, Cosentino F, Fouad-Tarazi F, et al. Sympathetic over Poddar G, Maitra SK. The effect of fresh leaves of activity in patients with chronic renal failure. N Engl J Azadirachta indica on glucose uptake and glycogen Med 1992;327:1912-8. content in the isolated rat hemi diaphragm. Bull Calcutta 58. Mitsnefes MM. Cardiovascular complications of pediatric Sch Trop Med 1987;35:8-12. chronic kidney disease. Pediatr Nephrol 2008;23:27-39. 43. Pari L, Satheesh MA. Antidiabetic activity of Boerhaavia 59. Barletta GM, Flynn J, Mitsnefes M, Samuels J,

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Friedman LA, Ng D, et al. Heart rate and blood The CKD-mineral bone disorder (CKD-MBD). Pediatr pressure variability in children with chronic kidney Nephrol 2010;25:769-78. disease: A report from the CKiD study. Pediatr Nephrol 67. Warady BA, Bakkaloglu S, Newland J, Cantwell M, 2014;29:1059-65. Verrina E, Neu A. Consensus guidelines for the prevention 60. Saland JM, Pierce CB, Mitsnefes MM, Flynn JT, Goebel J, and treatment of catheter-related infections and peritonitis Kupferman JC, et al. Dyslipidemia in children with inpediatric patients receiving peritoneal dialysis: chronic kidney disease. Kidney Int 2010;78:1154-63. 2012update. Perit Dial Int 2012;32 Suppl 2:S32-86. 61. Kidney Disease: Improving Global Outcomes (KDIGO) 68. Zimmet P, Cowie C, Ekoe JM, Shaw J. Classification CKD-MBD Work Group. KDIGO clinical practice of diabetes mellitus and other categories of glucose guideline for the diagnosis, evaluation, prevention, and intolerance. In: International Textbook of Diabetes treatment of chronic kidney disease-mineral and bone Mellitus. New York: Wiley; 2004. disorder (CKD-MBD). Kidney Int Suppl 2009;8:S1-130. 69. King H, Aubert RE, Herman WH. Global burden of 62. Larsson T, Nisbeth U, Ljunggren O. Circulating diabetes 1995-2025: Prevalence, numerical estimates, concentration of FGF-23 increases as renal function and projection. Diabetes Care 1998;21:1414-31. declines in patients with chronic kidney disease. Open 70. Oyedemi SO, Adewusi EA, Aiyegoro OA, Akinpelu DA Urol Nephrol J 2015;8:117-23. Antidiabetic and haematological effect of aqueous 63. Hasegawa H, Nagano N, Urakawa I, Yamazaki Y, extract of aqueous extract of stem bark of Afzelia african Iijima K, Fujita T, et al. Direct evidence for a causative (Smith) streptozotocin-induced diabetic Wister rats. role of FGF23 in the abnormal renal phosphate handling Asian Pac J Trop Biomed 2011;1:353-8. and vitamin D metabolism in rats with early-stage 71. World Health Organization. Prevention of Diabetes chronic kidney disease. Kidney Int 2010;78:975-80. Mellitus: Report of a WHO Study Group. Geneva: 64. Portale AA, Wolf M, Juppner H, Messinger S, Kumar J, WHO; 1994. Wesseling-Perry K, et al. Disordered FGF23 and mineral 72. Sandoval S. Pima Indian diabetes susceptibility metabolism in children with CKD. Clin J Am Soc differs significantly from susceptibility. Biochemistry Nephrol 2014;9:344-53. 2009;118:1-8. 65. Paoli S, Mitsnefes MM. Coronary artery calcification 73. Arky RA. Clinical Correlates of Metabolic Derangements and cardiovascular disease in children with chronic of Diabetes Mellitus. Complications of Diabetes kidney disease. Curr Opin Pediatr 2014;26:193-7. Mellitus. Philadelphia: W.B. Saunders; 1982. p. 16-20. 66. Hruska KA, Choi ET, Memon I, Davis TK, Mathew S. Cardiovascular risk in chronic kidney disease (CKD): Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S68 Antioxidant activity of Rajatachandrodaya rasa

Dinesh Kumar Verma1 , Santosh Kumar Maurya2 1Department of Rasa Shastra, Shanti Ayurvedic Medical College and Hospital, Ballia, Uttar Pradesh, India, 2Department of Dravyaguna, Shanti Ayurvedic Medical College and Hospital, Ballia, Uttar Pradesh, India

Abstract

Background: Ayurveda is a system of Indigenous Medicine which systematizes and applies the knowledge about health and disease. After the development of Rashasatra Ayurveda made a land mark in the history of medicine by making judicious use of Herbo-Mineral preparations in the treatment of many diseases without any untoward effects with high degree of safety and efficacy. Rajatachandrodaya is a Herbo- mineral preparation. It is being prepared by Kupipakva method. Hence in the present study Experimental evaluation of Antioxident activity is conducted to ORIGINAL ARTICLE ORIGINAL interpret its basis of pharmacological properties. Method: Radical Scavenging by DPPH Method and Nitric Oxide Scavenging Activity method were used for evaluation of antioxidant properties with Ascorbic acid as standard. Result: IC50 values were found to be 1256.52 µg/ml and 793.80 µg/ml in Nitric oxide Scavenging Activity and DPPH Method respectively. Conclusion: The current study shows that Rajata Chandrodaya Rasa exhibits antioxidant effects which may be responsible for therapeutic application in sexual problems and low sperm count.

Key words: Rajatachandrodaya Rasa, Ayurveda, Kupipakva, Antioxidant

INTRODUCTION agents, chelating agents for transition metals, quenchers of singlet oxygen molecules, and/or activators of antioxidative An antioxidant is a molecule that inhibits the defense enzyme system to suppress the radical damages oxidation of other molecules. Oxidation is a in biological systems.[2] Therefore, inhibition of free chemical reaction that transfers electrons or radical-induced oxidative damage by supplementation of hydrogen from a substance to an oxidizing antioxidants has become an attractive therapeutic strategy for agent. Oxidation reactions can produce free reducing the risk of these diseases. In recent years, it has been radicals. In turn, these radicals can start chain investigated that many plant species are serving as a source reactions. When the chain reaction occurs in a of antioxidants and received therapeutic significance. Several cell, it can cause damage or death to the cell. antioxidants of plant origin are experimentally proved and Antioxidants terminate these chain reactions used as effective protective agents against oxidative stress. by removing free radical intermediates and They play an important role in major health problems such inhibit other oxidation reactions. They do this as cancer, cardiovascular diseases, rheumatoid arthritis, by being oxidized themselves, so antioxidants cataracts, Parkinson’s disease, Alzheimer’s disease, and are often reducing agents such as ascorbic acid degenerative diseases associated with aging.[3] A great deal or polyphenols. In general, free radicals are of research has been carried out to evaluate scientific basis produced in large amounts during metabolic for the claimed antioxidant activity of herbal agents as in the disease conditions and have been implicated form of formulation. The aim of the present study is to and to in the causation of several problems such as evaluate the antioxidant activity of Rajatachandrodaya Rasa atherosclerosis, ulcers, asthma, cancer, cataract, (RCR). liver disease, and other inflammatory process.[1] Reactive oxygen species (ROS) are continuously The Rasausadhis are the backbone of the Ayurvedic produced during cell metabolism and under therapeutics.[4] These chiefly include metals, minerals, normal conditions; they are scavenged and converted to non-reactive species by different intracellular enzymatic and non-enzymatic Address for correspondence: antioxidant system. Antioxidants thus play an Dinesh Kumar Verma, Shanti Ayurvedic Medical College important role in the protection of the human and Hospital, Ballia, Uttar Pradesh, India. body against damage by ROS. Antioxidants Phone: +91-9140804759. may act as free radical scavengers, reducing E-mail: [email protected]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S69 Verma and Maurya: Antioxident activity of Rajatachandrodaya rasa

Table 1: In vitro antioxidant activity of RCR

Tablet IC50 value RCR µg/mL IC50 value of standard ascorbic acid µg/mL Nitric oxide (% inhibition) 1256.52 865.44 DPPH (% inhibition) 793.80 511.61 RCR: Rajatachandrodaya Rasa

Previously, we have reported the beneficial effect of RCR on spermatogenesis.[8] In the present study, we evaluate the RCR for its antioxidant properties.

MATERIALS AND METHODS

The RCR was obtained from the Department of Postgraduate Studies in Rasashastra, Ayurveda Mahavidyalaya, Hubli, Karnataka.

Methods

The antioxidant activity of RCR was evaluated by different in vitro methods which are given as follows. Figure 1: Effect of Rajatchandrodaya Rasa on nitric oxide scavenging activity Procedure for Nitric Oxide Scavenging Activity

The nitric oxide scavenging activity of RCR was determined according to the method (Green et al., 1982). Aqueous solution of sodium nitroprusside spontaneously generates nitric oxide (NO) at physiological pH, which interacts with oxygen to produce nitrate ions and which was measured colorimetrically. 3 mL of reaction mixture containing 2 mL of sodium nitroprusside (10 mM) in phosphate buffered saline and 1 mL of various concentrations of the RCR were incubated at 37°C for 4 h. Control without test compound was kept in an identical manner. After incubation, 0.5 mL of Griess reagent was added. The absorbance of the chromophore formed was read at 546 nm. The percentage inhibition of nitric oxide generation was measured by comparing the absorbance values of control and those of test compounds. Figure 2: Effect of Rajatchandrodaya Rasa on 2,2-diphenyl- Vitamin E (10, 50, 100, 200, 400, 800, and 1000 µg/mL) was 1-picrylhydrazyl free radical scavenging activity used as standard. The percentage nitric oxide inhibition was calculated from the following formula.[9] herbo-mineral and marine products, known for their quick action, tastelessness, and effective in minute dose.[5] In classical % nitric oxide inhibition = OD of control-OD of test ×100 age, herbal products were extensively used in all 8 branches of OD of control procedure for free radical scavenging by Ayurveda, and later during post-classical age, extensive research 2,2-diphenyl-1-picrylhydrazyl (DPPH) method was carried out by then Ayurvedic scholars, as a result potent and safe remedies were explored from metals and minerals. DPPH scavenging activity was measured by the spectrophotometric method. A stock solution of 25 mg of RCR is a one of Kupipakwa Rasayanas a unique method DPPH (150 µM) was prepared in 100 mL of ethanol. To the of preparation.[6] RCR is one such imperative Kupipakwa 0.2 mL of RCR of different concentrations, 3.8 mL of DPPH Rasayana, used for sexual disorder particularly erectile was added. Control without test compound was prepared in dysfunction (ED). It is formulated by two fundamental an identical manner. In case of blank, DPPH was replaced by substances of Rasashastra, i.e., Shudha Parada and Shudha ethanol. The reaction was allowed to be completed in the dark Gandhaka and Shudha Rajata. Several reports were published for about 20 min. Then, the absorbance of test mixtures was regarding beneficial effects of different antioxidants on ED.[7] read at 517 nm. The percentage inhibition was calculated and

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S70 Verma and Maurya: Antioxident activity of Rajatachandrodaya rasa expressed as percent scavenging of DPPH radical. Vitamin E CONCLUSION (10, 50, 100, 200, 400, 800, and 1000 µg/mL) was used as standard. The percentage DPPH inhibition was calculated The current study shows that RCR possesses antioxidant from the following formula.[9] effects which may be responsible for therapeutic application in sexual problems and low sperm count. % DPPH Inhibition = OD of control-OD of test ×100/OD of control REFERENCES

RESULTS 1. Lobo V, Patil A, Phatak A, Chandra N. Free radicals, antioxidants and functional foods: Impact on human Scavenging activity of RCR was enumerated in Table No., health. Pharm Rev 2010;4:118-26. Figure 1 and Figure 2. The composition of hydrogen peroxide 2. Lü JM, Lin PH, Yao Q, Chen C. Chemical and molecular into water may occur according to the antioxidant property mechanisms of antioxidants: Experimental approaches present in the RCR as it may be a good electron donors, they and model systems. J Cell Mol Med 2010;14:840-60. may accelerate the conversion of H2O2 to H2O. IC50 values 3. Lien AP, Hua H, Chuong PH. Free radicals, antioxidants were found to be 1256.52 µg/ml and 793.80 µg/ml in Nitric in disease and health. Int J Biomed Sci 2008;4:89-96. oxide Scavenging Activity and DPPH Method respectively 4. Gokarn RA, Rajput DS, Yadav P, Galib, Patgiri B, Prajapati PK, et al. Pharmaceutical standardization of svarṇa vaṅga. Anc Sci Life 2013;33:97-102. DISCUSSION 5. Chaudhary A, Singh N. Herbo mineral formulations (Rasaoushadhies) of ayurveda an amazing inheritance of RCR is one among the Dhatu sindhura. While mentioning ayurvedic pharmaceutics. Anc Sci Life 2010;30:18-26. about Chandrodaya with Swarna, there is mentioning that in 6. Gujarat Rajya Bhaisajya Semite. Swasth Mantralaya Gujarat similar way silver and other metals can also be used instead Rajya Ahmadabad, Bhaisajya Samhita. Ahmadabad: of gold and we can call it respective Dhatu Chandrodaya. We Supridentdense Press and Publication, I.A.S R; 2008. p. 268. get reference of RCR in Bhaisajya samhita,[6] he explains the 7. Zhang Q, Radisavljevic ZM, Siroky MB, Azadzoi KM. preparation in Sharava. Rajatachandrodaya also has been Dietary antioxidants improve arteriogenic erectile explained in Rasendra Sambhava along with other Dhatu dysfunction. Int J Androl 2011;34:225-35. Sinduras. Bhaishajya Sara Samgraha explains the Anubhuta 8. Joshi BB, Agnihotri P, Joshi A, Dinesh BS. Spermatogenic Yoga of Rajata Sindura, special feature in this reference, activity of rajatachandrodaya rasa. Int J New Tech Res quantity of Rajata is 4 times to that of Parada. Other than above, 2016;2:67-72. we do not get any classical references for the preparation of 9. Gupta DK, Maurya SK, Seth A. Effect of bhavana with Rajata Sindura, and by this, the procedure of Swarna Sindura amla juice on in-vitro Antidiabetic and antioxidant may be applicable to Rajata also. RCR is used in Jwara (fever), activity of Amalaki Emblica officinalis Gaertn. Indian J Dhwaj bhang (ED), Rajayaksma (tuberculosis), Rasayana Agric Allied Sci 2015;1:151-6. (rejuvenating agent), and Vajikarana (aphrodisiac). 10. Pirincci N, Yıldırım S, Tas A, Kuscu Y, Ozan T, Firdolas F, et al. Evaluation of prolidase activity, oxidative stress Oxidative stress plays an important role ED and sperm and antioxidant enzyme levels in testicular and penile generation. This affected more than about 150 million tissues after human chorionic gonadotropin treatment individuals worldwide.[10] Modern drugs used to cure ED and in rats by predicting infertility and erectile dysfunction. low sperm count have major systemic effects and produced Med Princ Pract 2018. several side effects. Therefore, alternative therapy is required nowadays. RCR shows antioxidant activity in both the assay. Its antioxidant potential may be responsible for therapeutic application of RCR. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S71 Review article on quality and safety of Ayurvedic formulation

Garima, Anoop Kumar Singh Department of Agadtantra, Rishikul Campus Haridwar, Uttarakhand Ayurved University, Harrawala, Uttarakhand, India

Abstract

Ayurveda, the divine science of healing has always for the well-being of the people and society. Classical formulations are amended from time to time according to the need of the sufferers. This flexibility has ensured its existence until today. Inclusion of Agadtantra in therapeutics further strengthened Ayurveda. Agadtantra

REVIEW ARTICLE REVIEW deals with Ayurvedic pharmaceutics, with the safety, efficacy, and quality preparation of drugs from metals and poisonous herbal drugs. According to WHO guideline, government of India prepared separate monograph of herbal drugs along with standard method of preparation of drug and guidelines in “Ayurvedic Pharmacopoeia of India,” everyone concerned to herbal drugs should compulsory have to follow these monographs of herbal drugs ensuring quality, safety, and efficacy nothing but quality control while preparation and identification and use of medicinal plants. WHO has given guidelines for general limits of contaminants of herbal drugs such as percentage of foreign matter, heavy metals, microbial load for crude drug, specific for internal or external use. Each drug not crosses these limits. If any drug reported similar character or values accordingly, then the drug is supposed to be a standard or quality drug. The prime objective of the pharmaceutical research is to produce a safe, effective, and quality drug. Worldwide the hazards of the drugs are monitored stringently to reduce the patient’s mortality or the untoward, adverse effects or unwanted effects of the drugs or therapeutic procedures. For the regulation of safety, and efficacy issue the control and check on the ASU drugs through the pharmacovigilance programmed was essential.

Key words: Agadtantra, Ayurveda, Ayurvedic formulation, drugs, herbal formulation, pharmacovigilance, safety

INTRODUCTION taken in formulation form using the traditional system to made formulations. In developed or undeveloped countries found he WHO defines an herb as being fresh more use of Ayurvedic drugs over last few decades. Quality of or dried, fragmented or powdered plant Ayurvedic and herbal medicine is practiced on their experiences Tmaterial, which can be used in this crude for proper identification of plants; gradually regulation was state or further processed and formulated to put into force and the first organization. Regulation of this become the final herbal product. Ayurveda is a product first organized regulatory publication on herbal drug medical system primarily practiced in India that has been known for nearly 5000 years. It includes quality was the drugs and cosmetic acts 1940 and drugs and diet and herbal remedies while emphasizing the cosmetic rules 1945. Several reports are documental proven body, mind, and spirit in disease prevention that herbal drugs are not saved when not to be taken on the and treatment (Morgan, 2002). WHO has also proper formulation and purification procedures. Some are issued Guidelines for the Assessment of Herbal quite toxic in nature these drugs not to be purified properly Medicines (WHO, 1996). These guidelines it may cause harmful effects to the person. As a result, to find defined the basic criteria for the evaluation the quality, safety, and efficacy of Ayurvedic, as well as herbal of quality, safety, and efficacy of herbal formulations, is important for both consumers and health medicines with the goal of assisting national authority throughout the world.[1] regulatory authorities, scientific organizations and manufacturers in assessing documentation, submissions, and dossiers in respect of such Address for correspondence: products. Herbal medicine is abundantly available Dr. Garima, Department of Agadtantra, Rishikul Campus in India due to its various climatic zones. India Haridwar, Uttarakhand Ayurved University, Harrawala, has many species of plants, of which 20,000– Uttarakhand, India. Phone: +91-9410594950. 25,000 plants proven as medicinal values when E-mail: [email protected]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S72 Garima and Singh: Review article on quality and safety of Ayurvedic Drug formulations

Objectives Some adverse events reported in association with herbal products are attributable to problems of quality. Major The objectives are as follows: causes of such events are an adulteration of herbal products 1) Importance of the drug quality, safety, and efficacy of with undeclared other medicines and potent pharmaceutical Ayurvedic and herbal formulations. substances, such as corticosteroids and nonsteroidal anti- 2) To described the pharmacovigilance in form of drug inflammatory agents. Adverse events may also arise from adverse effects. the mistaken use of the wrong species of medicinal plants, 3) To described the shelf life of the drugs. incorrect dosing, errors in the use of herbal medicines both by health-care providers and consumers, interactions with According to the WHO guideline, government of India other medicines, and use of products contaminated with prepared separate monograph of herbal drugs along with potentially hazardous substances, such as toxic metals, standard method of preparation and guidelines in “Ayurvedic pathogenic microorganisms, and agrochemical residues. Pharmacopoeia of India,” everyone concerned to herbal Misidentification of the medicinal plant species, plant drugs should compulsory have to follow these monographs materials were used for manufacturing herbal products, which of herbal drugs ensuring quality, safety, and efficacy nothing caused severe kidney failure in patients in several countries.[4] but quality control while preparation and identification and use of medicinal plants. Side Effect WHO has given guidelines for general limits of contaminants Any unintended effect of a pharmaceutical product occurs of herbal drugs such as percentage of foreign matter, heavy at doses normally used in humans that are related to the metals, microbial load for crude drug, specific for internal pharmacological properties of the drug. Herbal formulation or external use. Each drug not crosses these limits. If any which contains heavy metals is cause kidney failure and drug reported similar character or values accordingly, then liver damage in some consumers because they contain toxic the drug is supposed to be a standard or quality drug.[2] chemicals or react harmfully with other drugs. This is due to the lack of systematic observation has meant that even Good Manufacturing Practices (GMP) serious adverse reaction, such as the kidney damages.

It is a production and testing practices that help to ensure Adverse Event/Experience a quality product. Manufacturing processes are clearly defined and controlled. All critical processes are validated Any untoward medical occurrence that may present during to ensure consisting and compliance with the specification. treatment with a pharmaceutical product but that does not Manufacturing processes are controlled; any changes to the necessarily have a causal relationship with this treatment. process are evaluated. Changes that have an impact on the Serious adverse event of any untoward medical occurrence quality of the drugs are validated as necessary.[3] It ensured that, at any dose such as results in death, requires inpatient that consistently produced and control safety standard hospitalization or prolongation of existing, hospitalization, and minimizes the risks involved in any pharmaceutical results in persistent or significant disability/ incapacity. production. It also ensured the aspect of production from the starting materials, equipments and training and hygiene of the staff present in the pharmaceutical company. Adverse Reaction

Drug which has noxious and unintended was taken in the doses Safety form used in human for the prophylaxis, diagnosis, therapy of diseases for the modification of physiological function. Safety is a fundamental principle in the provision of herbal These are causes adverse drug reaction i.e. harmful to human. medicines and herbal products for health care and a critical An adverse reaction, the nature or severity of which is not component of quality control. These guidelines provide consistent with domestic labeling or market authorization, or practical technical guidance for monitoring the safety of expected from the characteristics of the drug. herbal medicines within pharmacovigilance systems. A recent study indicated that more than 70% of the German population reported using “natural medicines” and that, for Quality Assurance and Control most of them, herbal medicinal products were the first choice in the treatment of minor diseases or disorders. Quality assurance and control measures, such as national quality specification and standards for herbal materials, GMP for herbal Among consumers, there is a widespread misconception that medicines, labeling, and licensing schemes for manufacturing, “natural” always means “safe,” and a common belief that imports, and marketing, should be in place in every country remedies from natural origin are harmless and carry no risk. where herbal medicines are regulated. These measures are vital However, some medicinal plants are inherently toxic. for ensuring the safety and efficacy of herbal formulations.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S73 Garima and Singh: Review article on quality and safety of Ayurvedic Drug formulations

WHO guidelines are provided for safety and monitoring of The Prevention of Food Adulteration Act, 1954 herbal medicines under the pharmacovigilance system. Weak regulation and quality control may result in a high incidence Laws existed in a number of states in India for the prevention of adverse reactions attributable to the poor quality of herbal of adulteration of foodstuffs, but they lacked uniformity having medicines, in particular resulting from adulteration with been passed at different times without mutual consultation undeclared potent substances and/or contamination with between states. The need for central legislation for the whole potentially hazardous substances and residues. country in this matter has been felt 1937 when a committee appointed by the central advisory board of health recommended The quality control and standardization of raw drugs in “Adulteration of foodstuff and other goods” is now included process drugs and to worldwide acceptance of herbal drugs, in the constitution of India. This act related when contains any World Health Organization, have done compulsion of use poisonous and other ingredient which renders it injurious to of the standard drug to ensure, quality, safety, and efficacy health, if any colorings matter other than prescribed in respect of the drug which is long lasting and need of the time. thereof is present in the article, or if the amount of the prescribed The quality control and standardization of raw drugs, in colorings matters which present in the article are not within process drugs and finished products, are necessary. It can the limit of variability. The quality or purity of the article in be done with the help of modern scientific techniques for standard or its constituents are presents in quantities not within that purpose; different countries prepared the pharmacopeias the limit of variability, but which renders it injurious to health.[8] which include “monograph” of drugs indicating quality parameters and high standard for most of the herbal drugs Food Safety and Standard Authority of India and their products.[5] It is an autonomous body established under the ministry of health and family welfare, government of India. The FSSAI CENTRAL GOVERNMENT ACTS RELATED has been established under the food safety and standard act, TO DRUG 2006. Which is a consolidating statute related to food safety and safety and regulation in India. It contains the guideline for food safety research such as generate new knowledge Drug and Cosmetic Act 1940 that would help in continuously updating and upgrading food safety standard which is compatible with international It is an act of parliament of India which regulates the organizations. To carried out evidence-based studies for import, manufacture, and distribution of drugs in India. improving or building policies. They described the different The primary objective of an act is to ensure that the drugs standard for the different product such as dairy products and and cosmetics sold in India are safe, effective, and confirm analogs, fats, oils and fat emulsions, fruits and vegetables to state quality standards. The related drugs and cosmetic products, fish and fish products, salt, and spices. rules 1945 contain a provision for classification of drugs under given schedules, and there are guidelines for the storage, sale, display, and prescription of each schedule.[6] Pharmacovigilance All medicines for internal and external use of human being or animals and all substances intended to be used for or in WHO defines pharmacovigilance as “the science and the diagnosis, treatment, mitigation, or prevention of any activities related to the detection, assessment, understanding, disease or disorder in human being or animals, including and prevention of adverse effects or any other medicine- [9] preparation applied on the human body for the purpose of related problems” (WHO 2004, 1). repelling insects and mosquitoes. Pharmacovigilance is the science and activities relating to the detection, assessment, understanding, and prevention Section 157 in the Drugs and Cosmetic Rules, 1945 of adverse effects of drugs or any other possible drug- related problems such as Lack of efficacy reports and use The manufacture of be Ayurvedic and herbal drugs should of medicines for indications that are not approved and for be carried out in such premise and under such hygiene which there is the inadequate scientific basis. Somethings are conditions as are specified in schedule T(1A) for getting related to the pharmacovigilance like Case report of acute certificate of GMP of Ayurvedic drugs.[7] A graduate in and chronic poisoning, assessment of drug related mortality, pharmacy or pharmaceutical chemistry or chemistry or Drug abuse and misuse of medicine etc.[10] botany or a university recognized by the central government with experience of at least 2 years in the manufacture of Since 2003, national pharmacovigilance is functioning in India drugs pertaining to the Ayurvedic medicines. A qualified and it is under the central drug standard organization. They pharmacist in Ayurvedic system of the medicine possesses published the guidelines for the safety monitoring of herbal drugs experience of not <8 years in the manufacture of Ayurvedic in 2004. Worldwide the hazards of the drugs and medical therapies drugs as may recognized by the central government. are monitored stringently to reduce the patient’s mortality or the

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S74 Garima and Singh: Review article on quality and safety of Ayurvedic Drug formulations untoward, adverse or unwanted effects of the drugs or the drugs drugs. For quality drug and drug product, quality control or therapeutic procedures. Due to the popularity of the ASU techniques or standardization according to Ayurveda and drugs and due to increase in demand for these drugs from the modern is very necessary. However, practically due to the large community, the chances of adulteration and malpractice in the diversity in nature as well as the physical and mental buildup manufacturing and distribution are increased. Commercialization of human being different standard are applicable for a different in ASU drugs put forward the issue of safety and efficacy. The condition which is very difficult. The solution or a need of need to develop the national pharmacovigilance center for ASU time is that the ultimate objective of any herbal drugs is to drugs was addressed in the monitoring of the programmed perform a specific function according to its nature. Guidelines centrally. This program aims to keep the data of adverse drugs defined the basic criteria for the evaluation of quality, safety, reaction of herbal, mineral and metallic product.[11] and efficacy of herbal medicines with the goal of assisting national regulatory authorities, scientific organizations and manufacturers in assessing documentation, submissions, EXPIRY DATE OF AYURVEDIC DRUGS and dossiers in respect of such products. Herbal medicine is abundantly available in India due to its various climatic zones.

The Expiration Described in Ancient Ayurvedic Text Like REFERENCES 1. Churn (powder)- 2–4 months 1. Herbal formulations- shodhganga. Available from: • Lepa (Ointments) - 2 years shodhganga.inflibnet.ac.in>bitstream. • Danta manjana (tooth powder) - 2 years 2. Subhash R. Research Methodology and Medical 2. Gutika/tablet 5 years (herbal and mineral preparation) Statistics. 2nd ed. Printed. Pune-411033: Manakarnika • Gutika (herbal preparation) - 3 years Publication; 2013. p. 115. • Gutika (mineral preparation) - 10 years 3. Subhash R. Research Methodology and Medical 3. Guggulu tablets - 5 years Statistics. 2nd ed. Printed. Pune-411033: Manakarnika 4. Aveleha/Leham/Herbal jam/Paka - 3 years Publication; 2013. p. 120. • Khanda paka (haridra khand) - 3 years 4. WHO guidelines on safety monitoring of herbal 5. Lauha preparation - 10 years medicines in pharmacovigilance systems, WHO Geneva 6. Ghrita (herbal ingredient) - 2 years 2004, Available from-aaps.who.int>s7148e>s7148e. 7. Taila (herbal oil) - 3 years 5. Subhash R. Research Methodology and Medical 8. Arka (distilled herbal extract) - 1 year 12.[12] Statistics. 2nd ed. Printed. Pune-411033: Manakarnika Publication; 2013. p. 115-6. FINISHED PRODUCT 6. Drugs and Cosmetic act. 1940. Wikipedia. Available [13] STANDARDIZATION from: https:>en.m.wikipedia.org>wiki>Drugs. 7. The prevention of food Adulteration Act. 1954. Indian • Ayurvedic method - organoleptic features (panchbhautika) kanoon. Available from: https://indiankanoon.org>doc. • Shabda - short/long/even or uneven 8. The prevention of Food Adulteration Act. 1954. • Sparsh - internal/external Introduction. Available from: htpps://www.medindia.net/ • Roop - color indian_health_act/the-prevention-of-food-adulteration- • Ras - taste act-1954-introduction.htm. • Gandha - odor. 9. Research guidelines for evaluating the safety and efficacy of herbal medicines, essential medicines and Modern perspective - juice percentage, specific gravity, ph., health product information portal. 1993. p. 94. Available viscosity in form of property of liquid, time required to flow from-apps.who.int/medicinesdocs/en/d/jh2946e. from specific distance to specific distance. 10. Available from: http://www.apps.who.int>medicinedocs >documents. 11. Subhash R. Reaserch Methodology and Medical CONCLUSION Stastistics. 2nd ed. Printed. Pune-411033: Manakarnika Publication; 2013. p. 163. Ayurveda, the divine science of healing has always for the 12. Shelf life or expiration date of Ayurvedic medicine- well-being of the people and society. Classical formulations Easy Ayurveda, Available from: htpps://easyayurveda. are amended from time to time according to the need of the com>2010/12/05. sufferers. This flexibility has ensured its existence until today. 13. Subhash R. Research Methodology and Medical Inclusion of Agadtantra in therapeutics further strengthened Statistics. 2nd ed. Printed. Pune-411033: Manakarnika Ayurveda. Agadtantra, the unique Ayurvedic pharmaceutics, Publication; 2013. p. 108. deals with the safety, efficacy, and quality preparation of drugs from metals, minerals, animal products, and poisonous herbal Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S75 Treatment of migraine with indigenous medicinal plants: A review

Harendra Pathak, Ambrish Kumar Singh Department of Pharmacy Ayurveda, Pharmacy Ayurveda, Rajiv Gandhi South Campus, Banaras Hindu University, Barkachha, Mirzapur, Uttar Pradesh, India

Abstract

Migraine is one of the most severe types of neurological disorder. Common symptoms of migraine are blurred vision and vibration in sound. Some symptoms appear before the attack of migraine such as allergic reactions. The prevention of migraine involves mediation, yoga, use of herbal formulas, lifestyle modification, panchakarma, and

REVIEW ARTICLE REVIEW other holistic modalities to create a balanced physiology. This state of complete balanced in healing the body and mind can allow the illness to resolve and disappear the symptoms of migraine. Attack of migraine occurs due to the disbalance in Vata, Pitta, and Kapha (Tridosha) condition, but it can also be triggered by any one of the individual Doshas. Several indigenous medicinal plants are used for the treatment of migraine such as Mentha piperita, Brassica nigra, Calotropis procera, Cassia tora, Helianthus annuus, Moringa oleifera, Ocimum basilicum, and Piper longum.

Key words: Migraine, Menthapiperita, Surajmukhi

INTRODUCTION Asanas for migraine are Savasana, Urdhva Mukha Svanasana, Matsyendrasana, Paschimottanasana, Janusirsasana, igraine is a neurological disorder Uttanasana, Prasarita Padottanasana, Adho Mukha which originated half side severe pain Svanasana, and Virasana.[4] Meats, dairy products, and eggs Min head with various symptoms.[1] The are the best left off your plate permanently. Aside from being symptoms of migraine are feeling of blurred among the worst migraine triggers, they also tend to disturb vision, vibration sounds, colds of hands, mental your natural hormone balance, which contributes to migraines. confusion, nausea, vomiting, and dizziness. These symptoms may occur before the attack of the migraine. There are various factors such as Chrysanthemum indicum allergic reactions, bright lights, loud noises and C. indicum belongs to the family Compositae have several certain odors or perfumes, physical or emotional stress, changes in sleep patterns, smoking or vernacular names as Chrysanthemum (English), Shatapatri exposure to smoke, skipping meals, alcohol or (Sanskrit), and Chandramallika, Sphaeranthus indicus. [5,6] caffeine, fluctuations in menstrual cycle, birth Leaves of this plant showed antimigraine property. control pills, and headaches.[2] These are mainly two types of migraine. Most common type is Areca catechu “migraine without aura.” Pain will be one side (or) both side of head with symptoms of mood A. catechu belongs to the family Arecaceae have several slowing, nausea, photophobia, vomiting, and vernacular name as Betel Nut (English), Puuga (Sanskrit), fatigue. The second type of migraine with aura and Supari (Hindi). Its useful part is dried seed. The seed’s and this type of migraine symptoms raised before mainly contains tannin, alkaloids, terpenoids, flavonoids, 10–30 min of attack. This is a neurological amino acids, peptides, and phenols. Ethanol and aqueous phenomenon and it effects mainly on locomotors. extract of the seeds of A. catechu showed antimigraine The second type of migraine is depend on optic property.[7] stress and stages of migraine.[3] The prevention of migraine is learn to relax and reduces stress Address for correspondence: – try progressive muscles relaxation (contracting Dr. Ambrish Kumar Singh, Pharmacy Ayurveda, Rajiv and releasing muscles throughout your body), Gandhi South Campus, Banaras Hindu University, meditation, biofeedback, or joining a support Barkachha, Mirzapur - 231 001, Uttar Pradesh, India. group, avoid smoking, caffeine, alcohol, exercise E-mail: [email protected] regularly, and enough sleep each night. Different

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S76 Pathak and Singh: Indigenous medicinal plants for migraine

Mentha piperita for Cucurbitacins colosynthosides. Oil cooked root bark fruit juice, leaves applied on head to cure for migraine.[15,16] M. piperita belongs to the family Lamiaceae have several vernacular name as Peppermint (English), Vilayati Cassia tora (Sanskrit), and Pudina (Hindi). The volatile contains of menthol, menthone, and cineole showed migraine property. [8] C. tora belongs to the family Caesalpiniaceae have several The oil is used dhumpam. Mint essential oils are generally vernacular name as Ringworm plant (English), Chakramarda used externally for antipruritic, astringent, antiseptic, and (Sanskrit), and Panvad (Hindi). Seeds of this plant contained antimicrobial purposes, and for treating neuralgia, headaches, [9,10] phytochemical Cassiside, toralactone. 25 g seeds are made into and migraines. Topical (-)-menthol induces a sensation of paste with the help of water seeds are ground in “kanji” (gruel coldness by which itching (urticaria and pruritus) and pain is of beans) and applied on forehead to get relief from migraine. It reduced. This effect is mediated by the activation of TRPM8 plays a powerful role in the internal absorption of electrolyte in the receptors topically applicated peppermint oil is also used body. Its defect in man includes severe diarrhea and migraines.[17,18] against migraine and tension headache.[11]

Helianthus annuus Achyranthes aspera H. annuus belongs to the family Asteraceae have several A. aspera belongs to the family Amaranthaceae have vernacular name as Sunflower (English), Surajmukhi several vernacular name as Prickly chaff flower (English), (Sanskrit), and Hurhul (Hindi). Leaves and seeds of the plant Apaamaarga (Sanskrit), and Chichdha (Hindi). Seed of this contained diterpenoids, kaurenoic acid. Seed magnesium is plants contained phytochemicals, achyranthes oleanolic important for maintenance of nerve and muscle tone in body. acid glycosides, and amino acids. It is inhaled for relief Sunflower seeds contain substantial amounts of magnesium, to headache of migraine as well as stiffness. Apamarga hence, predicting their potential usefulness in bronchial asthma, Navanita, a preparation of Achyranthes aspera is used for the muscle cramps, hypertension, and migraine. Leaves juice is [12] treatment of migraine (Suryavarta). grinded together applied on head to relief for migraine.[19]

Brassica nigra Sesbania grandiflora

B. nigra belongs to the family Brassicaceae have several S. grandiflora belongs to the family Fabaceae have several vernacular names as Black mustard (English), Banarasi vernacular name as Sesbane (English), Munitaru (Sanskrit), Raai (Sanskrit), and Raee (Hindi). Seeds of this plant and Agastya (Hindi). Flower or leaf of the plant contained contained major chemical constituent gallic acid and leucocyanidin, cyanidin, and triterpenoids. Few drops of leaf quercetin. Pigeon’s and seed’s droppings, after grinding, or flower extract are put in the opposite nostril of migraine are applied on forehead relief for migraine. The leaves, pain giving immediate relief.[20] seeds, and stems have been shown to reduce the severity of asthma and high blood pressure, restore normal sleep attacks and prevent heart attack in patients suffering Sapindus mukorossi from atherosclerosis or patterns in women experiencing S. mukorossi belongs to the family Sapindaceae have several symptoms of menopause, and reduce the frequency of vernacular name as Soap nut tree (English), Arishtaka migraine.[13] (Sanskrit), and Reetha (Hindi). Fruits of the plant contained triterpenoid, sesquiterpenoid, saponin, and glycosides. The Calotropis procera solution made from the fruits of Sapindus species has been found to decrease behaviors associated with migraine in C. procera belongs to the family Asclepiadaceae have mice. Its fruits are ground with black pepper and few drops several vernacular name as Swallow wort (English), Tapana are poured in the nostrils to get relief from migraine pain.[6,21] (Sanskrit), and Madar (Hindi). Yellowish dried leaves of this plant mainly contain of ursane, triterpenoids. Mix few drops Moringa oleifera of latex in ash of cow dung; inhale the smoke to reduce the pain it is used as “nasya” for migraine.[14] M. oleifera belongs to the family Moringaceae Drumstick (English), (Sanskrit) Shigru, and Shajan (Hindi) leaves Citrullus colocynthis of the plant contained Vitamins A and C, proteins, amino acids, flavonoids, phenolics, glucosinolate, isothiocyanates, C. colocynthis belongs to the family Brassicaceae have several and thiocarbamates (niczinin A and B and niczimicin). It is vernacular name as Bitter apple (English), Chitraa (Sanskrit), initial trigger of migraine can be due to an increased release and Indrayan (Hindi). They are main chemical constituent of serotonin. This is a neurotransmitter, to cause localized

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S77 Pathak and Singh: Indigenous medicinal plants for migraine ischemia. There is also an increase in dopamine levels (Sanskrit), and Vana-Tulsi (Hindi). Leaf grinded with garlic as implicated by associated symptoms such as yawning, oil, is given topical.[26,27] nausea, vomiting, and gastrointestinal disturbances, as a result of which dopamine receptor antagonists are effective Clitorea ternatea therapeutic agents in migraine. It is used in laves juice.[22] C. ternatea belongs to the family Papilionaceae have Ocimum basilicum several vernacular name as Butterfly pea (English name), Vishnukranta (Sanskrit), and Aparajita (Hindi). They are main O. basilicum belongs to the family Labitate have several chemical constituent for inositol, hirsutene. In Ayurveda, the vernacular name as Sweet Basil (English), Barbari (Sanskrit), juice of root used in migraine the lepa of seed root when take and Tulsi (Hindi). Fruits of the plant contained estragole an equal quantity and applied as nasal or recommends the methyl chavicol, linalool, cineole, and germacren D. Flower dried leaf. They are showed migraine property.[28] powder is administered with honey.[23,24] Syzygium aromaticum Daucus carota S. aromaticum belongs to the family Myrtaceae have several D. carota belongs to the family Apiaceae have several vernacular name as Clove (English), Devakusum (Sanskrit), vernacular name as Carrot (English), Garjara (Sanskrit), and Lavang (Hindi). Major chemical constituents of clove are and Gajar (Hindi). Leaves of the plant contained carvacrol, thymol, and eugenol. Cloves are grinded in water [23] carotenoids, α-Pinene, and sabinene. Pure ghee is applied and the lepa is applied on the earlobes to cure migraine. on leaves and warmed over heat and crushed into paste. Two or three drops of its extract are put into nostrils and Terminalia chebula ear cures headache due to migraine. Leaves extracted with warm “ghee” and given in nose and ears to cure migraine T. chebula belongs to the family Combretaceae have several through sneezing.[25] vernacular name as Chebulic Myrobalan (English), Haritaki (Sanskrit), and Harad (Hindi). Seeds of the plant contained oleanolic acid; glycoside seeds are crushed hot in water and Eclipta alba applied for forehead relief for migraine.[29] E. alba belongs to the family Asteraceae have several vernacular name as Trailing eclipta (English), Bhringa (Sanskrit), and Bhangraiya (Hindi). The main chemical CONCLUSION constituent for wedelolactone and glycoside mixing black pepper powder in its juice, it is applied on forehead for Migraine is a disabling disease. Migraines are frequently relief in migraine 5 mL juice of fresh leaves is mixed prescribed multiple preventive therapy medications to deal with 5 mL goat milk. It is Luke warmed and two drops of with recurrent headaches. The curing Ayurveda opens new mixture are put in both nostrils twice a day for 5 days cures doors for the treatment of migraine and other type of headaches. migraine.[25] Ayurvedic treatments are holistic therapies that are tailored to the individual since according to Ayurvedic medicine; everyone is a unique combination of five elements and three Piper longum life source energies (vata, pitta, and kapha). In Ayurveda, various techniques are used such as nutrition, lifestyle P. longum belongs to the family Piperaceae have several modifications, herbs, panchakarma, yoga, meditation, color vernacular name as Long pepper (English), Maagadhi therapy, and gem therapy to relief from migraine headaches. (Sanskrit), and Peepal (Hindi). Fruits of the plant contained These treatment approaches create a balanced physiology. piperine, P. longumine. Piperine is the major alkaloid of This state of complete balance in healing the body and mind peppers. Peppers and “bach” are given in milk to cure migraine can allow the illness to resolve and symptoms disappears. pain. Chandramallika, Sphaeranthus indicus One teaspoonful Synthetic drugs used for the treatment of migraine have juice of flower and fruit is taken and four grinded black pepper several side effects but indigenous medicinal plants are free are added to it and it is taken twice for 5 days with the help of of all these side effects. water; it cures chronic headache as well as migraine.[25]

Ocimum Canum, Ocimum americanum REFERENCES

Ocimum canum belongs to the family Labitate have several 1. Pearce JMS. Historical aspects of migraine. J Neurol vernacular name as Hoary Basil (English), Kali-Tulsi Neurosurg Psychiatri 1986;49:1097-103.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S78 Pathak and Singh: Indigenous medicinal plants for migraine

2. Kasper DL, Braunwald E, Hauser S, Longo D, Jameson JL, HPLC method for determination of colocynthin in Fauci AS. Harrisons Principles of Internal Medicine. colocynth. Res J Pharm 2015;2:39-48. 16th ed. New York: McGraw Hill Professional; 2006 17. Okwu DE. Evaluation of the chemical. composition of 3. DeMaagd, G. The pharmacological management of indigenous spices and. flavouring agents. Glob J Pure migraine, part 1: overview and abortive therapy. Pharm Appl Sci 2001;7:455-9. Ther 2008;33:404. 18. Deshpande HA, Bhalsing SR, Recent advances in 4. Singh R. Swasthvritta Vigyana. Varanasi: Chaukhambha the phytochemistry of some medicinally important Sankrit Pratisthana; 2004. Cassia species: A Review. Int J Pharm Med Biol Sci 5. Raja Gopal PL, Herbs in Inflammation- A Review. Int J 2013;2:60-78. Ayurvedic Herbal Med 2013;3:1289-307. 19. Vogt TM, Ziegler RG, Graubard BI, Swanson CA, 6. Sridhar C, Krishnaraju AV, Subbaraju GV. Greenberg RS, Schoenberg JB, et al. Serum selenium Antiinflammatory constituents of Teramnus labialis. Int and risk of prostate cancer in U.S. blacks and whites. Int J Pharm Sci Res 2006;68:111-4. J Cancer 2003;103:664-70. 7. Bhandare A, Kshirsagar A, Vyawahare N, Sharma P, 20. Janani M, Aruna A. Review on Neutraceutical Valueof Mohite R. Evaluation of anti-migraine potential of Sesbania Grandiflora. World J Pharm Res 2017;6:804-16. areca catechu to prevent nitroglycerin-induced delayed 21. Arulmozhi DK, Veeranjaneyulu A, Bodhankar SL, inflammation in rat meninges: Possible involvement of Arora SK. Effect of Sapindus trifoliatus on hyperalgesic NOS inhibition. J Ethnopharmacol 2005;136:267-70. in vivo migraine models. Braz J Med Bio Res 8. Garg SC, Essential Oils as Therapeutics. Nat Prod 2005;38:469-75. Radiance 2005; 4:18-26. 22. Upadhye KP, Rangari VD, Mathur VB. Antimigraine 9. Foster S. Menthapiperita. In: Botanical Series. Austin: activity study of Moringa oleifera leaf juice. Int J Green American Botanical Council; 1990. p. 306. Pharm 2012;6:204-12. 10. Cowan MM. Plant Products As Antimicrobial Agents. 23. Das SK Vasudevan DM. Tulsi the Indian holy power Clin Microbial Rev 1999;12:564-82. plant. Natural Product Radiance 2006;5:279-83. 11. Heimes K, Hauk F, Verspohl EJ. Mode of action of 24. Nishida R, Bowers WS, Evans PH. Synthesis of highly peppermint oil and (-)-menthol with respect to 5-HT3 active juvenile harmones analogsm juvocimene Iand receptor subtypes: Binding studies, cation uptake by II, from the oil of sweet basil (Ocimum basilicum) L. J receptor channels and contraction of isolated rat ileum. Chem Ecol 1984;10:1435-1450. Phytother Res 2011;25:702-8. 25. Sahani S, Mall TP. Diversity of potent ethno-medicinal 12. Prasad PV, Subhaktha PK. APAMARGA (Achyranthes flora for headache from North-Tarai Forests of (U. P.) aspera Linn.) A medico-historical review. Bull Ind Inst India. Int J Interdiscip Multidiscip Stud 2013;1:33-46. Hist Med 2001;31:11-24. 26. Smita R, Sangeeta R, Kumar SS, Soumya S, Deepak P. 13. Ufelle SA, Neboh EE, Achukwu PU, Ghasi S. The An ethnonotanical survey of medicinal plants in effects of crude methanol seed extract of Brassica Semiliguda of Koraput District, Odisha, India. Bot Res juncea on hematological parameters in wistar rats. Br J Int 2012;5:97-107. 2011;2:123-6. 27. Chetty KM, Sivaji K, Rao KT. Flowering Plants of 14. Deepak P, Soumya S, Kumar SS, Raut S, Raut S. An Chittoor District, Andhra Pradesh, India. Students Offset ethno botanical survey of medicinal plants in semiliguda Printers 2008;256: 1-600. of Koraput District, Odisha, India. J Botany Res Int 28. Maity N, Nema NK, Sarkar BK, Mukherjee PK. 2012;5:97-107. Standardized Clitoria ternatea Leaf extract as 15. Khattak MI, Hameed RJ, Arfat Y. A study of some heavy hyaluronidase, elastase and matrix-metalloproteinase-1 metals found in medicinal plants (Euphorbia cornigera, inhibitor. Indian J Pharm 2012;44:584-7. Rhazya stricta and Citrullus colocynthis) in Turbat 29. Lokesh N. Versatile ayurvedic approaches for treating region of Balochistan with reference to prevention of migraine: A review. J Innov Pharm Biol Sci 2015;2: 68-7. environmental pollution. Pak J Bot 2015;47:1511-6. 16. Shekarchi M, Ramezany F, Shams Ardekani MR, Lamshöft M, Rastegar H, Eftekhari M, et al. An improved Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S79 Botanical pesticides from plants: The sustainable approach to pest management

Jai P. Rai1, S. K. Goyal1, Alok Kumar Singh2 1Department of Mycology and Plant Pathology, BHU-KVK, Institute of Agricultural Sciences, Banaras Hindu University, RG South Campus, Barkachha, Mirzapur - 231 001, Uttar Pradesh, India, Department of Plant Pathology, Faculty of Agriculture, Udai Pratap Autonomous College, Varanasi - 221 002, Uttar Pradesh, India

ABSTRACT

Plants are attacked by some organisms. Initially, the man attempted to annihilate or eradicate these organisms from the ecosystem itself, but soon we learnt that the task that we are pursuing is impossible to achieve as the

REVIEW ARTICLE REVIEW organisms have their own means and ways to survive almost any harsh situation they are exposed to. Considering nontarget hazardous effects of chemical pesticides the scientists sought for a safer alternative to this problem and one of them that seems to be promising is the use of pesticidal principles. The use of pesticides prepared from plant extracts and products of biotic origin is not a new thing to India. It dates as back as 4000 years, and this fact makes it quite probable that the knowledge and exploitation of toxicological properties of herbs have even older history. Much before Surpala’s authored “Vrikshayurveda,” which dates back to 1000 AD when fertilizers and pesticides were unknown; there remain Vedas which have ample description of sustainable agriculture and forestry. Botanical pesticides are more popular in developing countries where they are being used in their crude forms, without much refinement of the active principle. The higher cost of synthetic molecules for pest control is one of the major reasons for this. Majority of the farmers of this unorganized sector in developing countries cannot afford these pesticides and hence resort to their botanical alternatives for pest and disease control. Although, it is too early to declare botanical pesticides a replacement of synthetic ones, suitability of these pesticides in integrated pest management strategies is making them popular among people who are aware of the hazards of synthetic pesticides and are keen to pay higher for organic produce. Such economic drive behind botanicals seems to contribute substantially to not only their acceptance but also to make them a popular input for produce of prime quality.

Key words: Botanicals, integrated pest management, pest management, pesticides, plant protection, Sustainable agriculture

INTRODUCTION learnt that the task that we are pursuing is impossible to achieve as the organisms have their own means and ways to survive lants face several kinds of stress in their almost any harsh situation they are exposed to. It took almost entire lifespan. These may originate from more than half a century to realize the fact that what we need to biotic, abiotic, and mesobiotic agents. As do in not eradicate the “organism” responsible for or involved P directly or indirectly in the crop loss, but to manage the ‘loss’ much as biotic stress is concerned, plants are attacked by a number of organisms. These harmful itself. As soon as we realized the truth, our focus shifted from organisms come from both, the prokaryotic and the “organism” to the “loss.” But unfortunately, during this the eukaryotic category. Among prokaryotes, period of almost more than five decades, we had synthesized bacteria, and mollicutes are the principal chemical pesticides which were treated as “panacea” for all organisms that cause diseases in plants. Among kinds of ailments of plants. Owing to its quick and miraculous eukaryotes, fungi, nematodes, and insects are the major group of organisms that cause considerable Address for correspondence: loss to the plants and economic parameters Dr. Jai P. Rai, Department of Mycology and Plant thereby. This has compelled the people involved Pathology, BHU-KVK, Institute of Agricultural Sciences, in agriculture to resort to the measures that Banaras Hindu University (RG South Campus), can mitigate the aggressiveness and reduce the Barkachha, Mirzapur - 231 001, Uttar Pradesh, India. activity of these deleterious agents. Initially, the Phone: +91-9415816734. man attempted to annihilate or eradicate these E-mail: [email protected] organisms from the ecosystem itself, but soon we

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S80 Rai, et al.: Botanical pesticides for pest management effects this chemical option was so injudiciously exercised that momentum. The scientists of the world are cheering up for our entire ecosystem had to face its negative repercussions and any measure of pest control which gives some sustenance to quite paradoxically, the reports of pest resurgence increased agriculture. During the past quarter of a century, the scientific with increasing use of chemical pesticides due to the higher literature has revealed an array of secondary plant metabolites sensitivity of natural enemies to these chemicals. Moreover, is that exhibit promising toxicity to various plant pests and has been a harsh reality that handling of the synthetic pesticidal pathogens. Some of them have been isolated and their active molecule by private companies was used to fulfil their own principle is characterized across world laboratories. These vested marketing interests and, therefore, had little to do with principles have been formulated into pesticides much like ethics and safety of the society. This has been the reason that synthetic ones regarding ease of their applicability. Botanical banning a molecule by the governments always followed its pesticides are more popular in developing countries where extensive usage and losses to the ecosystem which could never they are being used in their crude forms, without much be compensated. Furthermore, incidences of development refinement of the active principle. The higher cost of of resistance in pests to chemical pesticides also increased synthetic molecules for pest control is one of the major substantially. The scientists, therefore, sought for a more reasons for this. Majority of the farmers of this unorganized safe alternative to this problem and one of them that seems sector in developing countries cannot afford these pesticides to be promising is use of pesticidal principles (also called as and hence resort to their botanical alternatives for pest and botanicals) from plants which not only favor natural enemies disease control. Although it is too early to declare botanical of the pest but also have long-term impact on pests negating pesticides a replacement of synthetic ones, suitability of the chances of development of resistance in pests against them. these pesticides in IPM strategies is making them popular among people who are aware of the hazards of synthetic pesticides and are keen to pay higher for organic produce. SOURCE OF INFORMATION/ Such economic drive behind botanicals seems to contribute METHODOLOGY substantially to not only their acceptance but also to make them a popular input for the produce of prime quality. The information on plants useful in management of crop pests has been collected from exhaustive survey of literature Plants and their Roles in Pest and Disease available across books, monographs, research papers, Management research papers, and review articles. Selective parts of such literature were carefully taken into account for preparation Plants are being used for pest control since inception of of the manuscript to avoid ambiguity and misinterpretation agriculture particularly following identification of potential of any kind. pests and realization of the losses owing to them. However, scientific studies on this aspect have been intensified since the last 150 years. The number of plant species which can be Historical Perspective useful in pest management is as much as 2121 and 1005 of them are known to exhibit insecticidal properties.[2] Further, Use of pesticides prepared from plant extracts and products 384 species have shown promising antifeedant properties for of biotic origin is not a new thing to India. It dates as back harmful insects and 297 species exhibited repellent properties. as 4000 years and this fact makes it quite probable that the However, 31 species possessed growth inhibiting properties knowledge and exploitation of toxicological properties and 27 species had exhibited attractant properties. Marigold of herbs has even an older history. Much before Surpala’s (Tagetes erecta) is known for its antinemic properties and root authored “Vrikshayurveda,” which dates back to 1000 AD[1] extracts of marigold or asparagus has been found nematicidal when fertilizers and pesticides were unknown, there remain in nature. Tobacco is credited to be as such the first botanical Vedas which have ample description of sustainable agriculture pesticide and during seventeenth Century and nicotine and forestry. Surpala’s recommendation to remove pests obtained from its leaves has been shown to kill plum beetles. (worms-krimi) gathered on a tree, smoking the infested tree Vegetable oils have been used since long against stored with mixture of white mustard, ramantha, vidanga, vaca, products pests. Neem and Tulsi/Basil (Ocimum sanctum) usana and water mixed with beef, horn of a buffalo, flesh of had been the plants which are recommended for household a pigeon and the powder of bhillata (bhallataka?) can help. cultivation in ancient Indian literature. It is, perhaps, their Similarly, creepers eaten away by insects should be sprinkled pesticidal properties that have been the prime reason for such with water mixed with oilcake. Worms on plant leaves can be recommendation. destroyed by sprinkling the powder of ashes and brick dust. Like Ayurveda, the oldest system of medicine, the wisdom Neem (Azadirachta indica) of ancient India is being welcomed by researchers who have realized the impermanence of the agrochemicals (majority Neem (A. indica A. Juss. syn. Melia azadirachta L.: Meliaceae) of which are based on petroleum products and are soon to or Indian lilac, has azadirachtin as its principal insecticidal be exhausted) and the trend to test the ancient knowledge of ingredient, which is a tetranortriterpenoid limonoid.[3] agricultural pest management in modern times has gained Although almost all parts of neem contain azadirachtin but

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S81 Rai, et al.: Botanical pesticides for pest management its highest concentration (0.2–0.6%) is found in its seeds,[4] Quassia (Quassia amara) popularly called Nimboli in Northern India. Apart from Quassia or bitterwood tree (Q. amara L.: Simaroubaceae), these principles, some other limonoids including meliantriol, a tropical forest shrub indigenous to Northern Brazil is nimbin, nimbidin and salanin are also found in traces[5] and another plant with pesticidal properties which has been contribute to overall bioactivity. Azadirachtin works against utilized effectively since before the development of synthetic pests in a number of ways and is known to express including insecticides.[13] Pesticidal sprays are traditionally formulated insect growth regulatory, antifeedant, repellent, fecundity, and by boiling quassia wood in water; the wood, depending on [6] fitness reducing and anti-ovipositional properties against a the age, containing 0.14–0.28% quassinoids that exhibit number of pests. Azadirachtin is effective against more than insecticidal activity. 500 species of insects[7] and primarily the orders Lepidoptera, [8] Diptera, Homoptera, Coleoptera, and Hemiptera. Apart Ryania (Ryania speciosa) from its insecticidal properties, azadirachtin has also been found to be antifungal, antibacterial, and antiprotozoan in R. speciosa Vahl., a member of Family-Flacourtiaceae is nature.[3] This is perhaps the most exploited plant product for native to South America, the woody stems of which contain plant protection and more than 100 commercial formulations alkaloids showing insecticidal activity. These alkaloids are of neem are being used worldwide.[9] collectively called ryanoids, the most active of them being ryanodine and 9,21-dehydroryanodine.[14] <1% of ryanoide is found in ground stem wood.[9] The insecticidal principle Pyrethrum (Tanacetum cinerariifolium) is active against a number of insect pests including corn Powder of dry pyrethrum (T. cinerariifolium: Compositae) earworm (Helicoverpa zeae), citrus thrips, and leaf-eating has been used for delousing children since 400 BC. Rotenone, beetles being effective by contact, by ingestion or both. obtained from the roots of a plant called timbo or jicama vines (Pachyrhizus erosus) was introduced around 1850. It is Essential oils from plants a broad spectrum insecticide and piscicide. It is an odorless, Essential oils chiefly from the Lamiaceae, Apiaceae, colorless crystalline isoflavone, and occurs naturally in the Myrtaceae, Laureaceae, Rutaceae, and Asteraceae families stems and seeds of several plants and also in roots of several have shown great insecticidal potential. These are the plants of Fabaceae family. For centuries, it has been used secondary plant metabolites being mixtures of volatile to kill fish by poisoning and had notoriety of strong “fish organic compounds. They are not only easy to extract but poison.” However, the first instance of its use as pesticide also are broad-spectrum in nature possessing antifungal, dates back to 1848 when plants containing rotenone were antibacterial, and antiviral properties apart from being used to kill leaf-eating caterpillars. Emmanuel Geoffroy, a French botanist, isolated the active principle in 1895 and called it “nicouline.” In 1902, Nagai Nagayoshi, a chemist Table 1: Number of plant species with properties from Japan isolated the compound in pure crystalline form useful in pest and disease management from Derris elliptica (called roten in Japanese), and he named Action against Number of plant the compound “rotenone.” Later, researchers established that pests species nicouline and rotenone were chemically the same compound. Insecticidal 1053 Sabadilla (Schoenocaulon officinale) Antifeedant 384 Repellent 297 Sabadilla being another plant of lily family (S. officinale Schltdl. and Cham.), a tropical plant from Central and Growth inhibitor 32 South America which Indian have been using against Attractant 27 various pests for centuries. Its seeds are grounded to yield Rodenticidal 29 insecticidal dusts. The alkaloids produced in sabadilla are Acaricidal 02 [10] collectively known as “veratrine.” Ripe and aged sabadilla Nematicidal 58 seeds contain alkaloids as much as 0.3% and it is known to Fungicidal 100 affect the membrane of nerve cells, causing a loss of nerve function, paralysis and death.[10] It becomes effective against Bactericidal 04 leafhoppers, caterpillars, thrips, squash bugs and stink Molluscicidal 06 bugs either by contact or by ingestion. Although, sabadilla Herbicidal 15 degrades rapidly when exposed to air and sunlight, has little Antiseptic 35 residual toxicity and considered among the least toxic of Piscicidal (Fish 147 botanical insecticides with an oral lethal dose50 of 4000– poison) 5000 mg/kg body weight[11] the major limitation of sabadilla Arrow poison 90 being used as pesticide in agriculture is that it is highly toxic to honeybees.[12] Poisonous 69

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S82 Rai, et al.: Botanical pesticides for pest management

Table 2: Important trees/shrubs and plants showing pesticidal properties Common Name Scientific name Family Plant parts used Active principle Neem A. indica A. Juss. Meliaceae Leaves, seeds, oil, Azadirachtin, Meliantriol, bark Nimbidin, Salanin, Nimbin Dharek Melia azedarach L. Meliaceae Leaves, fruits, bark Nimbolin A. Nimbolin B, Meliatoxin A1 Pongam Pongamia glabra Vent. Leguminosae Leaves, fruits, Pongamol, pongapin, P. pinnata L. seeds, oil, roots and pongaglabrone, flowers pongallone, pongone Custard Apple Annona squamosa L. Annonaceae Leaves and bark Annonin, squamocin Mahua Madhuca indica (Koenig) Sapotaceae Oil and cake α and ß‑amyrin, quercetin, Macbride M. longifolia Koen saponin‑A Derris Derris chinensis Leguminosae Roots Rotenone Quassia Q. amara Simarubaceae wood and bark Quassin, isoquassin, neoquassin and quassimarin Ardusa Ailanthus excels Rutaceae Leaves Ailanthone Eucalyptus Eucaluptus globulus Labill Myrtaceae Leaves and oil Camphene, limonene, linalool, α and ß‑ pinenes, α‑terpinol Moringa Moringa oleifera Lamk Moringaceae Flowers and Leaves Moringyne Khejri Prosopis juliflora (Sw.) Dc. Mimosaceae Leaves and seeds Juliprosopine, julifloridine, juliflorinine, prosopidione Nirgundi Vitex nigundoI Linn. Verbenaceae Flowers, leaves and Vitexin, Negundoside V. trifolia Linn. roots Pink oleander Nerium oleander L. Apocynaceae Leaves, flowers Oleanderol, oleanderin, yellow oleander Thevetia neriifolia Juss. ex seeds and whole oleanderolicacid Steud plants Clerodendron Clerodendron Verbenaceae Leaves Trans‑decalin, clerodin indicum (L. inn.) Kuntze Ipomoea Ipomoea fistulosa Mart. Ex Convolvulaceae Whole plant, leaves, Isopomin, ergine, Choisy I. cornea and flowers isoergine, ipalbidinium Murraya Murraya koenigii (L.) Rutaceae Leaves and bark Curryanine, cuyyrangine, murraxonin, murraynone Ryania R. speciosa Flacourtiaceae Roots, leaves, and Ryanodine stalks Glircidia Glircidia sepium (Jacq.) Leguminosae Leaves and bark Glericidin, sepinol, Kunth gliricidol Jatropha Jatropha curcas L. Euphorbiaceae Leaves, seed, seed Curcusone, jatrophol, cake, oil jatrophin Euphorbia Euphorbia tirucalli L. Euphorbiaceae Branch Euphorbosterol, euphorbol Bougainvillea Bougainvillea spectabilis Nyctaginaceae Leaves Isohamnetin, quercetin Willd B. glabra Datura Datura stramonium Linn. Solanaceae Leaves, roots, fruits, Hyoscyamine, atropine, dried seeds scopolamine (hyoscine) Tobacco Nicotiana tabacum L. N. Solanaceae Leaves, whole plant Nicotine, nornicotine, rustica L. anabasine Sweet flag Acorus calamus L. Araceae Rhizomes Calamol, β‑asarone, α asarone Lantana Lantana camera L. L. Verbenaceae Leaves, whole plant Lantalonic acid, lantic trifolia L. acid, ursolic acid stearoylglucoside (UASG) (Contd...)

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S83 Rai, et al.: Botanical pesticides for pest management

Table 2: (Continued) Common Name Scientific name Family Plant parts used Active principle Indian Aloe Aloe vera (L.) Burn. Aloe Liliaceae Leaves, rhizomes Aloesin, aloin barbadensis Mill. Calotropis Calotropis gigantean Ait. Asclepiadaceae Leaves, roots Calatropin, calatoxin Chrysanthemum Chrysanthemum Asteraceae/ Flowers, leaves, Pyrethrin I, Pyrethrin cinerariifolium (Trev.) Vis. Compositae roots II, Cinerin I, Cinerin II, Jasmolin I, Jasmolin II Adhatoda Adhatoda vasica Ness. Acanthaceae Leaves Vasicine, vasicinone, adhatodin Mint Mentha spicata L. Mentha Lamiaceae Leaves, flowers, Menthole, limonene, arvensis DC whole plant, oil dihydrocarvone, menthone Tulsi/basil Ocimum sanctum L. O. Lamiaceae Leaves, flowers, Juvocimene‑I, basilicum L. stems, whole plant, juvocimene‑II, ocimin oil Parthenium Parthenium hysterophorus Asteraceae Leaves, flowers, Parthenin L. whole plants Onion Allium cepa L. Alliaceae Bulb Oleic acid, cepocide‑D, α and ß‑tocopherols Garlic Allium sativum L. Alliaceae whole plant, bulbs, Allicin, diallyl sulfide and leaves, flowers diallyl disulfide Chillies Capsicum annum L. C. Solanaceae Leaves, fruits Capsicin frutescens L. Sabadilla Sabadilla officinarum L. Liliaceae Seeds Ceavadine, veratridine Tephrosia Tephrosia vogelii H. T. Papilionaceae Roots, pods Purpurin, pupurenone purpurea L. Pers. T. purpuretenin A and B candida (Roxb.) Marigold Tagetes erecta L. T. minuta Compositae Flowers, leaves, Mycene, tagetone, L. roots alljupatuletin Matsyagandhati Gynandropsis pentaphylla Capparidaceae Leaves, flowers, Kaempferol, α and DC whole plants ß‑amyrins, ß‑sistosterol Bhoyringani Solanum surrattense Solanaceae Roots leaves, Solasodine, solanolone, Burms. F. flowers, fruits, whole solasonine plant Lemon grass Cymbopogon marginatus, Gramineae Leaves, roots Cymbopogone, C. nardus (L.) Rendle cymbopogonol Turmeric Curcuma longa Linn. Zingiberaceae Rhizomes Curcumol, curcumin Ginger Zingiber officinalis Rosc. Zingiberaceae Rhizomes Gingerols, α‑Zingiberine, arcurcumene Vinca Catharanthus roseus (L.) Apocynaceae Leaves, roots whole Vincristine, vinblastine, G. Don plants vindesine Vilayati Tulsi Hyptis suaveolens L. Lamiaceae Leaves Hyptolide Sida Sida acuta Burm. F. S. Malvaceae Leaves, roots shoot Vasicinol, vasicine, cordata (Burm. F.) Waalkes vasicinone Kubi Leucas aspera (Wild) Lamiaceae Whole plant, leaves, Spreng flower Castor Ricinus communis L. Euphorbiaceae Leaves, oil Ricin, Ricinnie Chirata Swertia chirata Gentianaceae Leaves Mahogany Swietenia mahogoni Meliaceae Seeds A. indica: Azadirachta indica, Q. amara: Quassia amara, R. speciosa: Ryania speciose, T. cinerariifolium: Tanacetum cinerariifolium

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S84 Rai, et al.: Botanical pesticides for pest management insecticidal in nature. Since the compounds quickly Azadirachta indica (A. Juss.). Integr Pest Manage Rev biodegrade in the soil, these are considered environmentally 2000;5:57-66. friendly[15] and relatively non-toxic to fish and mammals.[16] 6. Schmutterer H. Properties and potential of natural These compounds have shown various activities including pesticides from the neem tree, Azadirachta indica. Annu insecticidal, larvicidal, ovicidal, antifeedant, and repellent Rev Entomol 1990;35:271-97. against a number of insect pests.[17,18] 7. Schmutterer H, Singh RP. In: List of Insects Susceptible to Neem Products. New York, USA: VCH Publication; 1995. Thus, we can see that the plant kingdom is the rich storehouse 8. Sadre NL, Deshpande VY, Mendulkar KN, Nandlal of biologically active compounds and various plant products DH. Male Azadirachta indica in different species. Proc. are in use for over a century in India and other countries to 2nd International Neem Conference Rauischholzhausen; minimize losses in crops and grain storage.[19] A database 1983. p. 482. of plants with various properties that are helpful in pest 9. Khater HF. Prospects of botanical biopesticides in insect management [Table 1] has been prepared.[20] pest management. Pharmacologia 2012;3:641-56. 10. Grdiša M, Gršić K. Botanical insecticides in plant This is a small list as compared to the projections being done protection. Agric Conspectus Sci 2013;78:85-93. after the first decade of twenty-first century. In Table 2, a 11. Dayan FE, Cantrell CL, Duke SO. Natural products in list of important plants/trees/shrubs is presented which have crop protection. Bioorg Med Chem 2009;17:4022-34. exhibited promising pesticidal activity.[18,21,22] 12. Weinzierl RA. Botanical insecticides, Soaps and Oils. In: Rechcigl JE, Rechcigl NA, editors. Biological and Future Prospects Biotechnological Control of Insect Pests. Boca Raton, New York, USA: Lewis Pubishers; 2000. p. 110-30. As we can see the growing awareness about hazardous 13. Macenbo F, Hilje L, Mora GA, Salazar R. Antifeedant effects of synthetic pesticidal molecules on ecology and activity of Quassia amara (Simaroubaceae) extracts on environment, one can very easily foresee the fact that the Hypsipyla grandella (Lepidoptera: Pyralidae) larvae. future of plant pest control is much more dependent on Crop Prot 2000;19:301-5. the plant community itself. Plants have evolved with their 14. Jeffries PA, Toia RF, Brannigan B, Pessah J, Casida JE. respective pests and pathogens and they have developed more Ryania insecticide: Analysis and biological activity of 10 or less a mechanism to fight these agents for their survival natural ryanoids. J Agric Food Chem 1992;40:142-6. and in this course of action, they have started biosynthesis 15. Misra G, Pavlostathis SG, Perdue EM, Araujo R. of some molecules that have different effects on different Aerobic biodegradation of selected monoterpenes. Appl kinds of organisms based on their relationship with the Microbiol Biotechnol 1996;45:831-8. host plant. However, this mechanism need to be employed 16. Koul O, Walia S, Dhaliwal GS. Essential oils as green with due knowledge of the active principle, its effects on pesticides: Potential and constraints. Biopestic Int target organisms and also, on nontarget species. Extensive 2008;4:63-84. toxicological studies are required to find suitably effective 17. Cetin H, Yanikoglu A. A study of the larvicidal activity yet safer molecules and plants seem to be a great resource of of Origanum (Labiatae) species from Southwest Turkey. these agents which have to play a pivotal role in designing J Vector Ecol 2006;31:118-22. the strategy of plant protection in the future. 18. Isman MB. Plant essential oils for pest and disease management. 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Azadirachtin: An update. potential of using indigenous pesticidal plants for insect J Insect Physiol 1993;39:903-24. pest control to small scale farmers in Africa. Am J Plant 4. Govindchari TR. Chemistry and biological investigations Sci 2015;6:3164-74. on Azadirachta indica (the neem tree). Curr Sci 1992;63:117-22. 5. Akhtar M. Nematicidal potential of the neem tree Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S85 Medicinal and nutritional benefits of oyster mushroom

K. K. Maurya, S. K. Goyal, Jai P. Rai, Sant Prasad, S. N. Singh Department of Krishi Vigyan Kendra, Banaras Hindu University-Krishi Vigyan Kendra, Institute of Agricultural Sciences, Banaras Hindu University, RG South Campus, Barkachha, Mirzapur, Uttar Pradesh, India

Abstract

Oyster mushroom is an edible fungus and has been classified as a vegetable in world foods. It belongs to genus Pleurotus. Mushroom fits in very well with sustainable farming systems with huge medicinal and nutritional importance. Oyster mushroom cultivation involves many steps, i.e., selection of substrate and suitable mushroom

REVIEW ARTICLE REVIEW strain, substrate preparation, its filling in polythene bags, growing the crop, and harvesting. The yield of oyster mushroom can be obtained 1–2 kg per bag from 45 to 60 days of crop duration. Oyster mushroom is the rich source of protein, vitamins, minerals, fiber, and other antioxidants such as selenium protect body cells from damage that might lead to chronic diseases and help to strengthen the immune system. Oyster mushroom is low in calories, fat free, cholesterol free, gluten free, and very low in sodium. Increasing the consumption of oyster mushroom appears to decrease the risk of obesity, diabetes, cancer, and heart disease and increase the immunity system of the body.

Key words: Dhingri, edible fungi, medicinal value, nutritional benefits, oyster mushroom, Pleurotus

INTRODUCTION and health. Subtropical and tropical climate of India is good for the growth of oyster mushroom as it thrives quite well in ushrooms are fleshy, spore-bearing a wide variation of temperature and moisture. reproductive structures of fungi. MThey are edible fungi of commercial In India, oyster mushroom is becoming a unique, non- importance, and their cultivation has emerged traditional cash crop under protected cultivation or being as a promising agro-based land-independent grown indoors. Scientifically, oyster mushroom is known enterprise.[1] Mushrooms are known to play an as Pleurotus ostreatus. In the local language, it is popularly important role in human health owing to their known as Dhingri. Bihar and UP are the emerging states in nutritional and medicinal properties. They oyster mushroom production. Its cultivation has increased are known to be a good source of protein, tremendously throughout the world during the past few vitamins, and minerals. In India, three types decades. Of total 6,161,000 tonnes edible mushroom produced of mushrooms are being cultivated, viz., white worldwide, oyster mushroom (875,600 tons) accounted for a button mushroom (Agaricus bisporus), paddy good share of 14.2% in 1997.[3,4] straw mushroom (Volvariella volvacea), and the oyster mushroom (Pleurotus spp.). However, Oyster mushrooms are the third largest cultivated mushrooms. white button mushroom being most popular of China is the largest producer of oyster mushroom and it these three is the most widely grown mushroom alone contributes to nearly 85% of the global production of on a commercial scale. approximately a million tonnes. The other countries which are known to produce oyster mushrooms include Taiwan, Oyster mushrooms are one of the most popular Japan, Korea, Italy, Philippines, and Thailand. Currently, edible mushrooms and belong to the mycological genus Pleurotus of the family Pleurotaceae. Address for correspondence: These mushrooms are a diverse group of Dr. Jai P. Rai, Department of Mycology and Plant saprotrophic fungi.[2] They were first cultivated Pathology, Banaras Hindu University-Krishi in Germany as a means of subsistence during Vigyan Kendra, Institute of Agricultural Sciences, World War I and are now grown commercially Banaras Hindu University, RG South Campus, around the world as food. Its cultivation is Barkachha, Mirzapur - 231 001, Uttar Pradesh, India. becoming increasingly popular in India with the Phone: +91‑9415816734. E-mail: [email protected] growing awareness of people about their food

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S86 Maurya, et al.: Medicinal and nutritional benefits of oyster mushroom

India produces only around 1500 tonnes of Oyster mushroom smooth being often somewhat lobed or wavy. The flesh of owing to low domestic demand. Another inhibiting factor in the mushroom is white in color, firm in texture, and varies its production in India is that export demand orders are quite in thickness owing to stipe arrangement. The gills of oyster large and cannot be met unless a linkage between producer, mushroom are white to cream in color and descend on the cooperatives, and exporters is developed. stalk if present.

Oyster mushroom can be cultivated on any type of lignocellulosic material such as paddy straw, sugarcane Cultivation of Oyster Mushroom leaves, banana leaves, sawdust, and rice hull. It can grow at Oyster mushroom is being cultivated in India, and with moderate temperatures, ranging from 20 to 30°C, couples with a relative humidity of 55–70%, on various agricultural growing awareness of food and nutrition in view of human waste materials used as substrate. Due to its flexible nature, health, it has been found to be promising in production and the Pleurotus genus is more cultivated than any other consumption across the country in the coming days. A brief mushroom species.[5] summary of its cultivation is being presented below.

Nutritional Value of Oyster mushroom and its Materials Required Health Benefits Substrate Mushrooms are a good source of protein, vitamins, and ‘Straw of wheat, paddy, jowar and bajra can be used as the minerals and are known to have a broad range of uses both as substrate for cultivation of oyster mushroom. food and as medicine. Oyster mushrooms are no exception to this, and they also offer much important nutritive and Mushroom spawn medicinal benefits to human body and health. A high nutritional value of Oyster mushrooms has been reported Good quality spawn of suitable strain should be purchased with protein (25–50%), fat (2.5%), minerals (potassium, from universities, Government mushroom spawn-producing phosphorus, calcium, and sodium) of about 8–12%, and centers, or other reliable sources. Vitamin D, C, B1, B5, and B6). P. ostreatus as a health promoter and environmental restorer is gaining more Substrate supplementation importance as compared to other medicinal mushrooms, Common supplements are wheat bran, rice bran, soybean resulting in an upsurge in their research and development cake, groundnut cake, maize meal, etc. Supplements are [6] activities during the past two decades. The inclusion thoroughly mixed with straw after pasteurization while of mushrooms in a regular diet may help significantly to spawning. overcome protein deficiency in the developing countries where good quality proteins from animal sources are Polythene bag either unavailable or unacceptable because of religious beliefs.[7] Mushrooms can be a good supplement to cereals[8] Transparent polythene bags of 80 cm × 40 cm or 60 cm × in enriching the human diet. Owing to their good nutritional 40 cm size are used for the purpose. and high digestibility values, mushrooms are gaining importance in today’s healthy diet. Methodology of Mushroom Production[13]

These mushrooms are a good source of non-starchy Substrate preparation carbohydrates, with a high content of dietary fiber and moderate quantity of proteins including most amino acids, Oyster mushroom can be cultivated on a large number of minerals, and vitamins.[9] The protein content varies from agro-wastes including straw of paddy, wheat, and ragi, etc. 1.6 to 2.5%, and the niacin content is about ten times Freshly procured good quality substrates are cut into small higher than that of any other vegetables.[10] However, oyster (2–3 cm) pieces with chaff cutter and are soaked in potable mushrooms have been reported to be rich in Vitamin B water contained in a drum for about 4–6 h. Afterward, the complex, Vitamin C, and several minerals vital for human substrate is dried in the shade for few hours to bring the health [Table 1].[11] moisture level down to 50–60%.

Making the polythene bags ready for filling Biology of Oyster Mushroom The polythene bags of 80 cm × 40 cm size or 60 cm × 40 cm Oyster mushroom has a broad, fan, or oyster-shaped cap size are taken and two holes of 10–12 cm diameter are made spanning 5–25 cm. Natural specimens of the mushroom in the center of the bag on each side. The bottom of the bag is have been found to vary from tan to dark-brown or white tied with jute thread to make the circular bottom flat for bed to gray in color. When young, the margin is in rolled and is when prepared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S87 Maurya, et al.: Medicinal and nutritional benefits of oyster mushroom

Table 1: Proximate composition of fresh and dried mushroom slices (%)[12] Mushroom samples Moisture content Crude protein Crude fat Crude fiber Total ash Carbohydrate Fresh 88.75 28.85 2.47 12.87 9.76 48.16 Dried 8.45 25.91 2.18 10.41 10.91 42.14

Spawning Mushrooms and Human Health The substrates such as wheat straw, paddy straw, and Mushrooms are rich source of protein, minerals, and other banana leaves (cut into small pieces) are filled in the antioxidants being almost perfect food for everyone. Often bottom of polythene bags to a height of about 5 cm. For grouped with vegetables, mushrooms provide many of the filling a single polythene bag, 1–1.5 kg of dry straw, 200 g nutritional attributes of produce as well as attribute more of each mushroom spawn, and supplement are used. Spawn commonly found in meat, beans, or grains. A growing is sprinkled uniformly over the surface of the substrate number of studies confirm that eating a variety of plant- after filling its first layer in the polythene bags. Then, next based foods is linked with reduced risk of lifestyle-related layer of substrates is spread to a height of approximately health problems. Mushrooms are low in calories, fat-free, 10 cm and an appropriate portion of spawn is sprinkled cholesterol-free, gluten-free, and very low in sodium, yet they over it. Thus, four layers of substrate and spawn are filled provide important nutrients including selenium, potassium in each polythene bag. Finally, the fourth layer of spawn is (8%), riboflavin, niacin, Vitamin D, and more. Mushrooms covered with substrates bits to a height of 5 cm and the tip are among those plant-based foods that help us avoid obesity, of the bag is tied with jute thread. In a bag 15–20, small cancer, heart disease, and mortality in general. holes (0.5 cm diameter) are made on all sides to facilitate gas exchange. Mushroom as a source of vitamins[14] Crop Management Oyster mushroom is a rich source of vitamin D, B1, B2, B3, B5, B9 and biotin’ with and as the following: Spawned bags, trays, or boxes are arranged in a dark • Vitamin D: Mushrooms are one of the few natural cropping room on raised platforms or shelves for spawn sources of Vitamin D, which is essential for healthy run (mycelial colonization) of the substrate. The optimum bones and teeth. temperature for mushroom production lies between 20 and • Vitamin B1 - Thiamin: Vitamin B1 controls the release 25°C and relative humidity is maintained to 70–80%. When of energy from carbohydrate, which is needed for the the mycelium has fully colonized the substrate, the fungus normal functioning of the brain and nervous system. is ready to form fruiting bodies. Contaminated bags with • Vitamin B2 - Riboflavin: Mushrooms are high in molds may be discarded while bags with patchy mycelial riboflavin that helps to maintain healthy red blood cells growth may be left for few more days to complete mycelial and promotes good vision and healthy skin. growth, and good ventilation should be maintained in the • Vitamin B3 - Niacin: Niacin helps to control the release cropping room. Bags are watered twice daily depending on of energy from protein, fat, and carbohydrate, which the weather condition. keeps the body’s digestive and nervous systems in good shape. Harvesting • Vitamin B5 - Pantothenic acid: It plays a number of essential metabolic roles in the human body, including The right shape for picking can be judged by the shape and providing assistance with the production of hormones, size of the fruiting body. Primordia appear within 6–8 days found naturally in mushrooms. of opening the bag that came to the harvestable stage • Vitamin B9 - Folate: Folate is an important factor in 5–6 days later. The mushrooms should be harvested when the healthy growth and development: pregnant women are cap begins to fold inward. Picking is done by twisting the encouraged to increase their folate to assist with growth. mushroom gently without disturbing the surrounding fruit • Vitamin H – Biotin: Biotin is essential in the metabolism bodies. Crop should not be watered before harvesting. The of proteins and carbohydrates and is just another second crop appears after 7–10 days. Hence, within 45–60- B-vitamin found in mushrooms. day crop period, 4–5 crops are expected. Mushroom as Source of Fiber and Minerals[14] Yield per bag Mushrooms are a valuable source of dietary fiber: A 100 g 1 kg - 2.0 kg fresh mushroom can be obtained from 45 to serving of mushrooms contains more dietary fiber (2.5 g) 60 days of crop duration. than 100 g of celery (1.8 g) or a slice of wholemeal bread

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S88 Maurya, et al.: Medicinal and nutritional benefits of oyster mushroom

(2.0 g). Mushrooms contain virtually no salt. The following Technol ;37:133-7. minerals are found in mushroom which plays an important 2. Kong WS. Description of Commercially Important role in growth and development of human body: Pleurotus Species. In: Choi KW, editor. Mushroom • Selenium: Mushrooms are one of the richest, natural Growers’ Handbook 1: Oyster Mushroom Cultivation. sources of selenium. This mineral works as an Seoul: Mush World; p. 54-61. antioxidant, protecting body cells from damage that 3. Pathmashini L, Arulnandhy V, Wijeratnam RS. might lead to heart disease and some cancers. Cultivation of oyster mushroom (Pleurotus ostreatus) on • Potassium: This important mineral aids in the sawdust. Cey J Sci (Bio Sci) ;37:177-82. maintenance of normal fluid and mineral balance, which 4. Chang ST. World production of cultivated and medicinal helps to control blood pressure. Mushrooms contain mushrooms in 1997 with emphasis on Lentinus edodes. more potassium than most other fruit and vegetables. Int J Med Mushrooms ;1:291-300. • Calcium: Calcium provides the structure for our teeth and 5. Rosado FR, Carbonero ER, Kemmelmeier C, Tischer CA, bones. 100g of mushrooms contains 2 mg of calcium. Gorin PA, Iacomini M. A partially 3-0-methylated (1→4) • Iron: Mushrooms are a source of iron, which is essential linked α‑d‑galactan and α‑d‑mannan from Pleurotus to most life forms and normal human physiology. ostreatoroseus sing. FEMS Microbiol Lett ;212:261-5. • Zinc: Found in almost every cell of your body, zinc 6. Patel Y, Naraian R, Singh V. Medicinal properties of stimulates the activity of approximately 100 enzymes, Pleurotus species (oyster mushroom): A review. World and among other things, supports a healthy immune J Fungal Plant Biol ;3:1-12. system. Zinc is found in mushrooms. 7. Dunkwal V, Jood S, Singh S. Physico-chemical properties • Magnesium: Magnesium helps to maintain normal and sensory evaluation of Pleurotus sajor caju powder muscle and nerve function, keep heart rhythm steady, as influenced by pre-treatments and drying methods. Br and improve healthy immune system; 100 g of raw Food J ;109:749-59. mushrooms contain 9 mg of magnesium. 8. Chang S, Buswell J. Mushroom nutriceuticals. World J Microbiol Biotechnol;12:473-6. 9. Croan SC. Conversion of conifer wastes into edible and CONCLUSION medicinal mushrooms. Forest Prod J ;54:68-76. 10. Ahmed M, Abdullah N, Ahmed KU, Bhuyan MH. Yield Mushrooms being a rich source of protein, vitamins, and and nutritional composition of oyster mushroom strains minerals essential for human health are now known as newly introduced in Bangladesh. Pesq Agropec Bras functional foods. Among the major kinds of mushrooms Bras ;48:197-202. produced in India, oyster mushroom is gradually becoming 11. Randive SD. Cultivation and study of growth of oyster popular since it can be produced at a small scale without the mushroom on different agricultural waste substrate and need of much detailed infrastructure and technical support. its nutrient analysis. Adv Appl Sci Res ;3:1938-49. The substrate or inputs for its production are usually farm 12. Tolera DK, Abera S. Nutritional quality of oyster wastes and locally available material which can be turned into mushroom (Pleurotus ostreatus) as affected by osmotic good profits by growing oyster mushroom. Oyster mushroom pretreatments and drying methods. Food Sci Nutr has important nutritive and medicinal properties that can well ;5:989-96. be utilized in keeping our society healthy and disease free. 13. Kannahi M, Sangeetha R. Production and nutritional status of oyster mushroom using agricultural wastes. World J Pharm Pharm Sci ;4:1876-84. REFERENCES 14. Anonymous. Available from: http://www. cairnsmushrooms.com.au/nutrition.html. 1. Shivhare U, Arora S, Ahmed J, Raghavan G. Moisture adsorption isotherms for mushroom. LWT Food Sci Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S89 Safety aspects of Ayurvedic formulations

Kavita Saini1, Usha Sharma Rasa-shastra and Bhaishajya Kalpana, Uttarakhand Ayurved University, Rishikul Campus, Haridwar, Uttarakhand, India

Abstract

Quality and safety are the most essential aspects and are the denominators in case of the drug. Drug safety is a basic and fundamental concept in medical practice. Ayurveda which is a holistic system of medicine has elaborated the causes and methods of drug-induced consequences along with preventive measures the available data in classical texts are scattered. The drug which is going to be administered into the human body should be standard and should not produce any kind of untoward effects after its administration. Since past decade, few scientists from different

REVIEW ARTICLE REVIEW corners of the globe started to raise concerns about the safety of these time-tested drugs and opined that there have been numerous reports of clinically significantly. The compilation an analysis along with modern concept drug safety is need of the hour. The present article deals with a review on evidence of different safety aspects of the Ayurvedic formulation.

Key words: Ayurvedic formulation, denominator, drug safety, quality

INTRODUCTION are added, and that of the finished product is of uniform size, weight, and content. Furthermore, the finished product afety is the state of being “safe” the should meet the labeled claim and deliver the expected and condition of being protected from harm promised physiological effect. The safety and benefits of the Sor other non-desirable outcomes. Safety new formulation, if significantly different from traditional of medicines and treatments has always been preparation, should be established by appropriate in vitro and on high priority in the tradition of Ayurveda. or in vivo testing. Ayurvedic system of medicine does not require any evidence to substantiate its efficiency since Formulation and manufacturing protocols should conduct all the fundamentals and principles are well according to strict GMP standards. At each step, from the documented in great treatises such as Charak acquisition of raw material to packaging finished product, samhita, Sushrutsamhita, Ashtanga granthavali, rigorous quality of control processes and standards should be and Anubhut yog. Although its richness and applied to ensure quality, purity, and consistency. wholesomeness are unquestionable, yet the issues on the safety of drug should be taken note of so It should be ascertained that unacceptable adulterants, as to ensure the quality, safety, and efficacy of the contaminations, and residues are not present in the raw Ayurvedic formulations and to protect the interests materials as well as extracts. of the consumers. Quality, safety, and benefit are issues which still pose a great challenge to the Development of Ayurvedic formulation was based on wide- Ayurvedic pharmaceutical industry. The quality ranging experiment and experiences. There was no need to of the product is dependent on the quality of validate the safety of these products but in current times, extraction, formulation, and manufacturing quality of drugs has been effected due to many factors processes. The safety of a product is directly related such as adulteration, contamination, and shortcuts being to its quality.[1] Hence, there is a need to modify followed instead of following the recommended methods regulatory guidelines for Ayurvedic formulation, of manufacturing so there is a need of evidence of safety of for example, good agricultural practices (good Ayurvedic formulations. laboratory practices [GLP]), good manufacturing practices (GMP), and GLP. New guidelines should embody the principle for Ayurvedic therapeutics Address for correspondence: and guidelines to encourage the global acceptance. Kavita Saini, Rasa-shastra and Bhaishajya Kalpana, Uttarakhand Ayurved University, Rishikul Campus, Manufacturers need to verify that the correct Haridwar, Uttarakhand, India. amounts of an ingredient of the formulation E-mail: [email protected]

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Evidence of Safety of Ayurvedic Medicine[2] need of the hour in Ayurveda. Pharmacovigilance plays an important role in optimizing drug safety and improving Traditional use treatment outcomes. It describes the possible side effects that can occur with different therapeutically useful Ayurvedic medicines have been traditionally used for drugs.[4] thousands of years in India. About 80% of the population in India depend on traditional medicines. Out of which Toxicity studies[5,6] 70% people do not go to physician and use these traditional medicines in the form of home remedies on their own. It The predominant concern of all national and international means that they use Ayurvedic medicines on a daily basis drug regulation is to ensure the safety of marketed in some other form. This is important evidence of safety medicinal product during a normal condition of use. The of Ayurvedic medicine going by their traditional usage goal of toxicity testing is to identify the hazardous agents, pattern. to define the condition (dose, time, route of exposure, the susceptible species, etc.) under which they will exert Method of preparation[3] their toxicity and estimate the potential effect on human health. Standard packages are there for preclinical safety The herbo-mineral products are processed in a way that evaluation studies expected to be performed before a eliminates the toxic properties of the metals. Most of the candidate drug can be evaluated in humans. Organization mineral/metals are used only after they are converted into for economic cooperation and development (OECD, bhasma by Marana. Before Marana, mineral/metals are 1981) and committee on the proprietary medicinal product thoroughly purified by classical process called Shodhana. (Charles worth and Griffin, 1989) have been established to By Shodhana process, mineral/metals lose the physical help harmonize the data requirement for different countries impurities present in them and became available in pure form with regard to regulation of drugs. OECD member for further processing. countries have recognized the unique opportunity for international harmonization of test methods. Besides, this [3] Objectives of Shodhana since government and industry are increasingly concerned • To convert the inorganic substances into organo-chemical with quality of studies on which hazards assessment are or herbo-mineral so that bhasma process become easy. based, several OECD member countries have to establish • To enhance the existing medicinal properties and criteria for the performance of these studies and then reducing harmful properties. with the changing regulatory climate the introduction of • To reduce toxicity of drugs. “GLP” have a major impact on the modern approach to • To make bhasma process easy. toxicological investigation. • To remove water of crystallization e.g, alum, borax and making them lighter. Ayurvedic formulations do contain toxic substance metals, • To remove adulterants e.g kampillak. etc., which if not used according to principles may show symptoms of toxicity.

Adverse Drug Research Monitoring Manufacturing of Ayurvedic medicine is controlled by drugs and cosmetic act of India. However, there are certain ADRs play an important role in assessing patient safety. In conditions, which a manufacturer has to meet before being fact, the classics emphasize the importance of drug processing granted manufacturing permission. As such there are no in ensuring the safety of the drug. Otherwise, also drug safety guidelines to conduct toxicity studies on Ayurvedic medicines is inherently related to its structure and composition may in India. Recently, Department of Ayush has issued draft it be a plant, animal, mineral sourced, or a synthetic drug. guidelines for conducting safety studies on Ayush drugs. Structure and composition of the drug, in turn, are a result However, Indian Council of Medical Research has issued of the processing through which the drug (final product) has preliminary guidelines as below.[7] been produced. Deviation is, however, small it may appear it is likely to result in a structural change in the final product Acute and repeated dose toxicity studies for the different which may compromise the safety of the drug. Hence, it is dose patterns of different herbo-mineral formulations were very necessary that the manufacturers must be very much carried out on both the sexes of different species of animals careful in the processing of drug. as per guidelines of schedule Y of the drug and cosmetic act 1940, in the accredited laboratories by reputed pharmacies of Pharmacovigilance is a science related to the detection, India. Administration of the dose was done through different assessment, understanding, and prevention of adverse routes in the animals. The results obtained from these studies effects or any other drug-related problems. One of its show that the aforesaid products are totally safe for human aims is early detection of unknown adverse reactions use in the prescribed dosage. In few animals treated with and detection of an increase in the frequency of (known) very higher dosage (10 times the prescribed dose) of the adverse reactions. Practice of pharmacovigilance is the formulations, minor changes were observed in hematological

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S91 Saini and Sharma: Evidences of the safety of ayurvedic medicines parameter, but these changes were found reversible within a Adulteration stipulated period.[8,9] As far as safety issues Rasaushadhi is concerned they are more a result of adulterants/contaminations and improper Factors Responsible for Toxicity of Ayurvedic processing and microbial load. These issues can be definitely Medicines tackled successfully if the operating procedures are standardized and monitored carefully. Improper manufacturing process The Charak Samhita has classified physician into three Ayurvedic products sometimes are adultered with similar categories; genuine physicians, feigned physician, and looking cheaper alternatives also. This can easily be pseudo-physician.[10] Due to socioeconomic reasons quackery controlled by strict GMP norms implementation. in the name of indigenous system of practitioners is also one important factor in certain parts of India. Ayurvedic pharmacology describes the possible side effects that can occur with different therapeutically useful drugs. Ayurvedic products sometimes are adulterated with similar Further, it also describes ways, including manufacturing looking cheaper alternatives also. These practices though not techniques, to minimize these side effects. common can easily be controlled by strict GMP norms. Ayurvedic literature prescribed various texts for proper Contaminants preparation of bhasmas such as Varitar, Rekhapoorn, Apunarbhav, Uttam, Niruttha, Nischandra, and Nisswadu. lrrational use of Ayurvedic medicine It reflects that our ancient Manishish were fully aware Following factors are very important with respect to rational of the toxicity of Rasaushadhis; hence, they have paid consumption of Ayurvedic medicine. attention to their safety profile. Not only this but also • The vehicle, for example, honey and water. they have described equipments for the manufacture of • Relationship with food - there are 10 different timing of such preparation. In spite of following all prescribed taking the medicine as per Ayurveda.[11] procedure strictly, there is possibility of toxicity due to a. Abhukta (early morning empty stomach) use of improper raw material and processing observation. b. Pragbhukta (immediately before food) Moreover, one problem arise in the form of toxicity due to c. Adhobhukta (immediately after food) drug to drug interaction. It should be sincerely observed d. Madhya bhukta (midway in the meal) and studied accordingly.[12] e. Antara bhukta (between morning meal and evening meal) Characterization of Ayurvedic Drug with Advanced f. Sabhukta (with food or mixed in food) Analytical Techniques g. Samudag bhuta (before and after intake of light meal) Regulatory measure even though bhasmas and heavy metals h. Muhur-Muhur (with food or without food) are an inherent part of Ayurvedic medicine, there is restriction i. Sagras (with every bite or with some of the bites) on the amount of metal that is allowed in a Ayurvedic product. j. Grasantar (between subsequent bite). The Government of India, Ministry of Health and Welfare, • Improper dose Department of Ayush, has come out with a notification • Incompatible formulation - though Ayurvedic physicians with permissible limits for the four heavy metals. Final always take care for any incompatible formulations. formulation can be tested for four metals nanoparticles can This is of particular concern when therapies are used have according to the ordinance. The four metals are arsenic incorrectly, are abused or administered improperly, or (As), lead (Pb), mercury (Hg), and cadmium (Cd).[13] are prescribed by unqualified practitioners. Quality of Ayurvedic Medicine DISCUSSION Maintaining quality of Ayurvedic medicine is of prime importance. After almost 30 years of effort, government Every system of medicine has efficacy versus toxicity. Charka of India has developed Ayurvedic Pharmacopoeia of India mentioned that every drug is a poison and every poison is a giving the quality standards of certain raw materials. Since drug, what matters are a dose hence he has suggested this Ayurvedic system of medicine covers a large number aspect for the therapeutic use of the drug (C.S 1; 125). of ingredients and formulations, generation of quality specifications of all the ingredients and formulations is an Safety and efficacy of a drug mainly depend on the method uphill task and will take its own time. GMP guidelines for of preparation. It is well-known fact that the modernization in Ayurvedic system of medicines in India have recommended the pharmaceutical industry leads to deviation in the classical implementation of quality control measure as well. method of preparation.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S92 Saini and Sharma: Evidences of the safety of ayurvedic medicines

To assess the quality of a finished product, there should be Department of Pharmaceutics. Institute of Technology; some basic standard as well as method of preparation. There 2012. are several parameters for testing quality of a chemical 2. Katiyar CK, Gaurav S. Safety Aspects of Rasa-aushadhis. drug. A specific method for each and every preparation and DIL, Sahibabad: Dabur Research and Development some basic standards of finished products are mentioned in Centre; 2008. Ayurvedic text to maintain their quality. This information may 3. Joshi D. Rass-Shastra (English Edition). 1st ed. Varanasi: vary from text to text. To overcome this problem, Sharangdhara Chaukhambha Orientalia; 2006. mentioned detailed information about various formulations 4. World health Organization. Quality Control Methods with respect to their methods of preparation as well basic for Medicinal Plant Materials Revised Draft Update. standards and are documented in Sharangdhara Samhita. Geneva: World health Organization; 2005. 5. The OECD Series on Principles of Good Laboratory Practice and Compliance Monitoring No.1 Environmental CONCLUSION Monograph No.45.1992. 6. Neeraj S. Division of Toxicology. Lucknow: Central To ensure the safety of drugs, it is very important to understand Drug Research Institute; 2015. and study the principles of drug safety mentioned in Ayurveda and 7. Vijay M. Drugs and Cosmetics Act. Lucknow: 1940 to follow the does and do not during prescription and consultation. Published by Eastern book Company; 2003. Ayurveda has got vast resources of the medicinal products in 8. Indian Council of Medical Research. Ethical Guidelines the world. Its herbal medicines are quite safe and free from any for Biomedical Research on Human Subjects. New Delhi: untoward effects. These drugs can be digested and assimilated Indian Council of Medical Research; 2000. in the body more easily due to having similar biomorphic 9. Kamdev D. Safety Profile of Rasausadhis (Herbomineral constitution. However, our Rasaushadhis is another treasure of Formulation) Need of the Hour for Global Acceptance. therapeutics, which can be given in smaller doses and having Puri Orissa: Gopabandu Ayurvedic Mahavidyalaya; prompt therapeutic efficacy, they can be stored for long time 2008. without declining their potency. Our Maharishis had described 10. Agnivesha A. Charak Samhita,Vol-1 Sutrasthana, so many parameters to establish the safety profile of these drugs. English Translation by R.K Sharma and Bhagwan If these classical principles were followed strictly in the light of Das, Reprint Edition, Varanasi: Chaukhambha Sanskrit latest technology, the outcome will be worth mentioning. Series; 2014. 11. Samhita S, Edited by Ambika Data Shastri Part 1. It is important that all the above factors are integrated and a Varanasi: Chaukhambha Sanskrit Sansthana; 1995. strategic approach to validate Ayurvedic drugs and ensuring 12. Tomer GS. Safety Profile of Rasaushadies in Present their safety and efficacy. Perspectives. Handa Allahabad: State Ayurvedic College and Hospital; 2008. 13. Gogtay NJ, Bhatt HA, Dalvi SS, Kshirsagar NA. The REFERENCES use and safety of non-allopathic medicine. Drug Saf 2002;25:1005-19. 1. Mishra B, Sanjay T. Ayurvedic Formulations; Current status and Guidelines for their Advancement. Varanasi: Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S93 A review on quality, safety, and legalization for herbal medicines

Lalchand Sahu1, Archana Sahu2, Joshi Pravin Kumar1, Rout Om Prakash1 1Department of Dravyaguna, Government Ayurved College, Raipur, Chhattisgarh, India, 2Department of RSBK, Government Ayurved College, Raipur, Chhattisgarh, India

Abstract

With the growing awareness of health care and safety aspects, people are moving toward Herbal products. In the past few decades, market of herbal and traditional medicines (TM) has grown up leap and bound. Till recently Ayurvedic medicines used to be prepared by the practicing physician himself for the use of his patients. In ancient

REVIEW ARTICLE REVIEW time collection, manufacturing and other processes was done by Vaidya’s in smaller quantity and proper season and used locally. There are 9000 licensed pharmacies in India. Although there is Global interest, there is a concern about Untested medicine Unregulated medicine Quality Standardization Clinical safety and Efficacy. The use of ineffective, poor quality, harmful medicines can result in the therapeutic failure, exacerbation of disease, resistance to medicines, and sometimes to death. Adulteration, substitution, ignorance of dealers creates problems; hence, it has become necessary to standardize the quality and safety assurance measures so as to ensure supply of medicinal plants of good quality. In view of the present trend of commercialization in the preparation and marketing of Ayurvedic medicines and to ensure the interests of the profession and public, the Government of India considered it expedient to utilize the existing law which controls the standards of allopathic drugs, namely, the Drugs and Cosmetics Act, 1940, to also control, in a limited measure, the Ayurvedic, Siddha, and Unani drugs by amending the Act. Govt. needs to establish strong regulatory authorities to ensure the quality, safety, and efficacy of herbal drugs.

Key words: Ayurveda, herbal drugs, quality, standardization

INTRODUCTION toxic, and also which processing methods or mixtures had to be used to meet steady and ideal results. Even in an ancient he term “herbal drugs” denoted by means cultures, ethnic, ancestral, or tribal people collect information of plant or part of plants that have been related to herbal plant and developed which is defined herbal Tconverted into phytopharmaceuticals by pharmacopeia.[2,3] simply means of processes involving collection or harvesting, drying, and storage.[1] Medicinal The World Health Organization (WHO) has individual herbal plant has play an important role in world health. drugs as whole, labeled medicinal products that have robust They are circulated worldwide, but they are most ingredients, aerial or secret parts of the whole plant or other rich in tropical countries. It is noted that about plant material or mixture of them. WHO has a set of specific 25% of all modern medicines are indirectly or Guidelines for the evaluation of the safety, efficacy, and Quality directly obtained from higher plants. The use of of herbal drugs or herbal medicines. WHO find out that 80% of herbal drugs as medicine is the ancient form of the world people currently use herbal medicine or drugs for the health care known to delicacy and it is used in most important health cares. Herbal drugs are a main constituent all cultures throughout history. Ancient humans in usual medicine and a general ingredient in Homeopathic, well known their dependence on nature for a Ayurvedic, Naturopathic, and in another medicine system. Herbs good healthy life and since that time humankind are usually measured as safe toxicity, side effects of allopathic depended on the variety of plant resources for drugs have led to more increased in a number of herbal drugs food, shelter, clothing, and medicine to cure manufacturers. For the past few years, herbal drugs have been immensurable of diseases. Led by nature, taste, and experience, primeval men and women Address for correspondence: cured illness using plant parts, animal parts, Dr. Lalchand, Department of Dravyaguna, Government and minerals that were not a part of the usual AyurvedCollege, Raipur, Chhattisgarh, India. diet. Primeval persons learned by trial and Phone: +91-9522555475. error basis to identified beneficial plants with E-mail: [email protected] helpful effects from those that were inactive or

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S94 Lalchand, et al. : Standardization of herbal drugs mostly used by the people with no prescription, leaves, stem, meet the requirements of safety and efficacy laid down in the bark, flower, seeds, roots, and extract of all these have been used national regulations for herbal medicines. in herbal drugs over the thousands of their use.[4,5] Category 2: Herbal Medicines In Systems

CLASSIFICATION OF HERBAL DRUGS In this category medicines such as Ayurveda, Unani, and Siddha medicines which have been used for a long time and • Ayurvedic herbalism: It is derived from the Sanskrit are documented with their special theories and concepts are word “Ayurveda” which means “The science of life,” categorised. which is originated in India more than 4000 years ago. • Chinese herbalism: It is a element of traditional related medicine. Category 3: Modified Herbal Medicines • African herbalism: Western herbalism is originated from Rome, Greece and then multiply to North, Europe, and These are herbal medicines as described above in categories 1 South America. and 2, except that they have been modified in some way either • Ayurvedic and Chinese herbalism has produced shape or form including dose, dosage form, mode of administration, into extremely sophisticated system of diagnosis, herbal medicinal ingredients, methods of preparation, and identification, and treatment over the centuries. It should medical indications. They have to meet the national regulatory have the long-term and effective history of results. requirements of safety and efficacy of herbal medicines.

Advantages of Herbal Drugs Category 4: Imported Products With A Herbal Medicine Base 1. Low cost of production. 2. They may have fewer side effects. This category covers all imported herbal medicines including 3. Effective with chronic condition. raw materials and products. Imported herbal medicines must 4. Widespread availability. be registered and marketed in the countries of origin. The safety and efficacy data have to be submitted to the national authority of the importing country and need to meet the Disadvantages of Herbal Drugs requirements of safety and efficacy of regulation of herbal medicines in the recipient country. 1. Lack of dosage instruction. 2. Poison risk associated with wild herbs. 3. Can interact with other drugs. Requirements For Assessment of The Safety of 4. Inappropriate for many conditions. Herbal Medicines 5. Some are not safe to use. Safety category Herbal drug technology includes all the steps that are involved A drug is defined as being safe if it causes no known or in converting botanical materials into medicines, where potential harm to users. There are three categories of safety standardization and quality control with proper integration of that need to be considered, as these would dictate the nature modern scientific techniques and traditional knowledge will of the safety requirements that would have to be ensured. remain important.[6] • Category 1: Safety established by use over long time • Category 2: Safe under specific conditions of use (such Classification of Herbal Medicines herbal medicines should preferably be covered by well- established documentation) The classification of herbal medicines is based on their origin, • Category 3: Herbal medicines of uncertain safety (the evolution, and the forms of current usage. safety data required for this class of drugs will be identical to that of any new substance) Category 1: Indigenous Herbal Medicines Specific Requirements For Assessment of Safety Historically used in a local community or region and is very of Four Categories of Herbal Medicines well known through long usage by the local population in terms of its composition, treatment, and dosage. Detailed • Category 1: Indigenous herbal medicines - if the information on this category of TM, which also includes medicines in this category are introduced into the market folk medicines, may or may not be available. However, if or moved beyond the local community or region, their the medicines in this category enter the market or go beyond safety has to be reviewed by the established national the local community or region in the country, they have to drug control agency. If the medicines belong to safety

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S95 Lalchand, et al. : Standardization of herbal drugs

category 1, safety data are not needed. If the medicines Table 1: WHO guidelines for standardization of belong to safety category 2, they have to meet the herbal drugs usual requirements for the safety of herbal medicines. Medicines belonging to safety category 3, i.e., “herbal Parameters Description medicines of uncertain safety,” will be identical to that Botanical Organoleptic evaluations, foreign of any new substance. matter, microscopic observation • Category 2: Herbal medicines in systems - the medicines Physicochemical TLC, ash, extractable matter, water in this category have been used for a long time and content, and volatile matter have been officially documented. Review of the safety Pharmacological Bitterness value, hemolytic value, category is necessary. If the medicines are in safety astringency, swelling index, foaming categories 1 or 2, safety data would not be needed. If index the medicines belong to safety category 3, they have to Toxicological Pesticide residues, arsenic, heavy meet the requirements for safety of “herbal medicines of metals uncertain safety.” Microbial Total viable aerobic compound, • Category 3: Modified herbal medicines - the medicines contamination pathogens, aflatoxins have to meet the requirements of safety of herbal Radioactive medicines or requirements for the safety of “herbal contaminations medicines of uncertain safety,” depending on the modification. • Category 4: Imported/exported products with a herbal (2002) with 52 monographs of widely used medicinal plants medicine base - exported products shall require safety found in India. The latest available scientific data have been data, which have to meet the requirements for the safety incorporated in these monographs. ASU Drugs Technical of herbal medicines or requirements for safety of “herbal Advisory Board mentioned in section 33-C. medicines of uncertain safety,” depending on the safety The ASU Drugs Consultative Committee-mentioned in requirement of the importing/recipient countries.[7] section 33-D. Misbranded drugs-mentioned section 33E. Adulterated drugs-mentioned in section 33EE. WHO GUIDELINES ON HERBAL Spurious drugs-mentioned in section 33EEA. MEDICINES Regulation of Manufacture of ASU Drugs-Section-33-EEB The WHO has given Guidelines for assessing the quality of states the regulations on manufacture and sale of ASU drugs. botanical materials mainly emphasized the need to ensure the quality of medicinal plant products using the modern A. Requirements of factory premises and hygienic techniques and applying suitable standards. In 1997, the WHO conditions described in schedule 1 (Rule 157) developed draft guidelines for methodology on research and B. Manufacture on more than one set of premises evaluation of TM. A typical monograph for herbal drugs as C. Prohibition of manufacture and sale of certain per the WHO guidelines is mentioned in Table 1.[8] Ayurvedic, Siddha, and Unani drugs-mentioned in section-33-EEC D. Power of Central Government to Prohibit Manufacture, HERBAL DRUG REGULATIONS IN INDIA etc., of ASU Drugs in Public Interest-mentioned in section-33-EED5. Recognizing the global demand, Government of India has realized good manufacturing practices for the pharmacies • Government analysts-mentioned in section 33F manufacturing Ayurvedic, Siddha, and Unani (ASU) • Inspectors-mentioned in section 33G medicines to improve the quality and standard of drugs. The • Penalty for manufacture, sale, etc., of Ayurvedic, Siddha, new rules came into force from June 2000 as an amendment or Unani drug in contravention of this Chapter-As to the Drugs and Cosmetics Act, 1940. Department of Indian prescribed under section 33-I Systems of Medicine and Homeopathy is trying to frame • Penalty for subsequent offences-As mentioned in safety and efficacy regulations for licensing the new patent section 33J and proprietary botanical medicines. Indian Pharmacopoeia • Confiscation-As mentioned under the section 33K covers few Ayurvedic medicines. Monographs have been • Application of provisions to Government departments - As given for some ayurvedic drugs such as clove, guggul, mentioned in section 33L opium, menthe, and senna. The Ayurvedic Pharmacopoeia of • Cognizance of offenses - As mentioned in section 33M India gives monographs for 258 different ayurvedic drugs. • Power of Central Government to make rules - As The standards mentioned are quite inadequate to build mentioned in section 33N quality of the botanical materials. Indian Drug Manufacturers • Power to amend First Schedule - As mentioned in Association has published Indian Herbal Pharmacopoeia section 33-O.[9]

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Steps of Standardization of Herbal Drugs CONCLUSION

1. Standardization of raw drugs - this includes the Herbal, Herbal drug standardization is very important for the safety mineral, and animal origin drugs. and efficacy of the drug. The routine methods of the herbal 2. Standardization of process procedure to prepare drug standardization address quality related issue using formulations - this includes the purification, etc., botanical and organoleptic parameters of crude drugs, and procedures to prepare a particular formulation. chemo-profiling assisted characterization with spectroscopic 3. Standardization of finished products - this includes a techniques, but the new era of herbal drug standardization quality of finished products. includes pharmacognostical, chemical, biological, biopharmaceutical, and molecular approaches. Herbal drug Parameters For Standardization of Herbal Drugs standardization should be done through multiple modes as the concentration of the phytochemicals varies according to The development of parameters for quality control of herbal climate, soil, and environment. Newer aids of research should drugs is a big task involving biological evaluation for a be used to identify minute variations. Various regulatory particular disease area, chemical profiling of the raw material authorities and industry are trying to address this issue of quality and laying down specifications for the finished product. and efficacy. Regulatory authorities of different countries have Therefore, the word “standardization” should encompass contributed in developing guiding principles addressing issues the entire field of study from birth of a plant to its clinical related to these aspects of botanical medicine. This review application. The herbal drug assessment in Ayurveda is discusses various regulatory issues related to the quality of about the whole drug rather than concentrating on the herbal drugs. As ayurvedic drugs are also included in the active principles or phytoconstituents, thus finer methods Drugs and Cosmetics Act, 1940 the drugs have to be safe and of standardization should be developed. General testing effective at the same time. This brings about the need for finer parameters for characterization and standardization of herbal standardization of herbal drugs. These guidelines are may be medicines are given in Table 2.[10] applicable to uplift quality of herbal medicines globally.

Table 2: General testing parameters for characterization and standardization of herbal medicines Testing parameters Guidelines General data Geographical GAP Harvesting time Harvesting process GMP Processing Identity Macroscopic According to pharmacopeias Microscopic Chemical TLC and DNA fingerprints Purity Foreign matter According to pharmacopeias Ash/sulfated ash Content of extractable matter Water content Assay Constituents with known therapeutic activity (biomarker) According to pharmacopeias Constituents with unknown therapeutic activity (marker substances) Titrimetric Photometric HPLC/GC/TLC Contaminants Pesticides Ph. Eur. Heavy metals Recommended limits for herbal drugs (oct. 91) Aflatoxins Regulation on aflatoxins (Nov. 90) Microbiological purity Ph. Eur. 1997 Suppl. 1999 Radioactivity GMPs: Good manufacturing practices, GAP: Good agricultural practices

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REFERENCES 7. Guidelines for the Regulation of Herbal Medicines in the South-East Asia Region Developed at the Regional 1. EMEA. Quality of Herbal Medicinal Products. Workshop on the Regulation of Herbal Medicine. Guidelines. London: European Agency for the Evaluation Bangkok. New Delhi: World Health Organization, of Medicinal Products (EMEA); 1998. Regional Office for South-East Asia; 2003. Available 2. Ji HF, Li XJ. Zhang HY. Natural products and drug from: http://www.searo.who.int/LinkFiles/Reports_ discovery. Eur Mol Biol Organ 2009;10:194-200. TradMed82.pdf. [Last accessed on 2018 Mar 18]. 3. Ahemad I, Aqil F, Owais M, editor. Modern 8. Warude D, Patwardhan B. Botanicals: Quality and Phytomedicine. Weinheim: Wiley-VCH Verlag regulatory issues. J Sci Ind Res 2005;64:83-92. 9. GOI Deptt of Ayush, MHFW, Pharmacopoeial Laboratory Gmbh&Co. KGa A; 2006. for Indian Medicines. Legal Status of Ayurvedic, 4. Abhishek K, Ashutosh M. Sinha BN. Herbal drugs- Siddha and Unani Medicines. Ghaziabad: GOI Deptt of present status and efforts to promote and regulate Ayush, MHFW, Pharmacopoeial Laboratory for Indian cultivation. Pharm Rev 2006;6:73-7. Medicines; 2005. 5. Maiti B, Nagori BP, Singh R. Recent trends in herbal 10. Honwad SV. A Hand Book of Standardisation of drugs: A review. Int J Drug Res Technol 2011;1:17-25. Ayurvedic Formulations. 1st ed. Varanasi: Chaukhambha 6. Sharma RK, Arora R. Herbal drugs: Regulation across Orientalia; 2012. the globe. Herbal Drugs-A Twenty First Century Perspective. 1st ed. New Delhi: Jaypee Brothers Medical Publishers (P) Ltd.; 2006. p. 625-7. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S98 Market study of Pushkarmool (Inula racemosa Hook. f.) an important Himalayan herb

Lalit Nagar1, Ringzin Lamo2 1Department of Dravyaguna, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India, 2Department of Agadtantra, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

Introduction: Due to excessive deforestation and extreme weather conditions adulteration of Himalaya herbs is rampant. There are about 50 medicinal plants from the Himalaya which are extensively used in Ayurvedic formulations, of which 32 plants are scarce and found adulterated in the market study. Moreover, to our RESEARCH ARTICLE misfortune, medical practitioners started depending on the traders for obtaining the raw materials. Hence, the need for identification of these herbs through botanical surveys, pharmacognostic studies, and the assessment of the quality of the material available in a particular area or market is essential. Materials and Methods: The genuine root samples of Pushkarmool, i.e., roots of Inula racemosa were collected from Bhadarwa District. Doda State - Jammu and Kashmir along with its mentioned adulterants are collected from its native habitat. Market samples of Pushkarmool from six major markets from all over India were collected and compared with the genuine samples. Results: Samples from five markets of India matches with the Pushkarmool, i.e., roots of I. racemosa whereas samples from one market could not be identified. Quality of the market samples along with the price of the drug varies from market to market. Discussion: This exclusive dependence on traders has created serious malpractice of adulteration and selling of substandard medicinal plant raw materials in the market.

Key words: Adulteration, market study, pushkarmool

INTRODUCTION 32 plants are scarce and found adulterated in the market study (Healing Herbs of Himalaya CCRAS Publication). lpine range of Himalaya is the One of the important aspects which have added misery source of many valuable herbs used to the identification of some of the important medicinal Aextensively in Ayurvedic, Tibetan plants or raw materials are an interruption in the traditional and Chinese system of medicine. Major part practice of Ayurveda. Moreover, to our misfortune, medical of the year, these hills are kept under ice, practitioners started depending on the traders for obtaining and for the vegetative growth, herbs get only the raw materials. Hence, the need for identification of these 5–6 months. Furthermore, these herbs are herbs through botanical surveys, pharmacognostic studies, present in the limited pocket which leads to and the assessment of the quality of the material available in the scarcity of Himalayan herbs. However, a particular area or market is essential. due to the globalization demand is increasing and production is decreasing. This decrease The botanical source of drug “Pushkarmool” as per the API in production gives chance to the raw drug Part I Vol. IV Page no. 116 is root part of Inula racemosa traders to adopt unscrupulous trade. Modern- Hook. f., belonging to the family Asteraceae found in alpine day ayurvedic physician depends on these Western Himalayas at an altitude ranging from 1800 to drug traders for procurement of herbs. Moreover, treatment with adulterated drugs Address for correspondence: leads to therapeutic unpredictability. Due to Lalit Nagar, Department of Dravyaguna, Faculty of excessive deforestation and extreme weather Ayurveda, Institute of Medical Sciences, Banaras Hindu conditions adulteration of Himalaya herbs is University, Varanasi, Uttar Pradesh, India. rampant. There are about 50 medicinal plants Phone: +91-9646170067. from the Himalaya which are extensively E-mail: [email protected] used in Ayurvedic formulations, of which

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4800 m above mean sea level. Pushkarmool is well known whereas Yogaratnakar described Kustha and Erandamool both in the Ayurvedic and Tibetan medicine. as the substitute for Pushkarmool. Other authors such as Adhamalla, Gangadhara, and Shivdas Sen also indicated Kustha in place of non-availability of Pushkarmool. Vaidya Aim and objective Bapalal is of the opinion that Pushkarmool is a variety of Kustha. Dr. Vaman Ganesh Desai, the author of “Aushadhi There is a vast document available with regard to the Sangraha” considers Pushkarmool to be Iris germanica and morphology of green drugs. However, for physicians who also consider this as Balvacha (Haimavati vacha and Sweta are totally dependent on the market for the procurement of vacha). He also considered I. racemosa as Rasna. medicinal plant raw materials, it is not of much relevance even if he has sound knowledge of identification of green Most researches have described the English name of drug. Different parts of medicinal plant raw materials, in Pushkarmool as “Orris root.” Infect “Orris root” is the root dry form, show different features most of which are being of Iris florentiana Linn. In the local market of Mumbai, common to many drugs thus creating a lot of confusion and Maharashtra, mostly the root of I. germanica is sold as Orris controversy in the identification of the crude drug. Same is root. Considering the pharmacological properties, the root of the case with Pushkarmool (I. racemosa). Hence, to check I. germanica has close resemblance with Kustha; thus, it is the status of Pushkarmool in markets a market study was considered as an appropriate substitute. Some people use the done by the author in the Department of Dravyaguna, NIA, root of “Nelumbium speciosum” i.e., kamal as pushkarmool, Jaipur, in the year 2012, which covers six major markets from which is absolutely incorrect.[3] all over India. Samples of Pushkarmool collected from all the markets were compared with the genuine source collected Dr. Bapalal Vaidya mentioned I. racemosa under the name from its native habitat. of Rasna.[4] Roots of Saussurea lappa of the same family which constitutes the drug Kustha is commonly found mixed Pushkarmool, i.e., root of I. racemosa Hook. f. can be with commercial samples. A study done, in 2010, in the identified organoleptically by following points. Roots are Department of Dravyaguna, NIA, Jaipur, scholar found that hard, stout, cylindrical, and twisted and having brown or in the markets of Delhi, Kolkata, and Bengaluru S. lappa were dark khaki color outer surface and inner exposed part is being sold under the name of Pushkarmool and in the market light yellow or khaki in color. After breaking, cutting portion of Jaipur Withania ashwagandha, i.e., Nagori Ashwagandha shows outer thin dark brownish colored ring, i.e., periderm, was being sold. followed by a yellowish colored woody portion with fine radical striation and centrally located pith with numerous small yellowish-white dot-like structures. It is predominantly Collection of genuine sample bitter in taste with a slightly sweet taste at the start. Smell is characteristic and smells such as somewhat camphor and The genuine root samples of Pushkarmool, i.e., roots of lighter than the smell of kustha. I. racemosa were collected from Bhadarwa District Doda State - Jammu and Kashmir. An authentic source of roots of Inula royleana and Kustha, i.e., S. lappa roots were collected Substitutes/adulterants from the hills of Shatargala Tehsil - Bhaderwa District Doda State - Jammu and Kashmir. After collection Herbarium was The major problem in the field of Indian medicine is confusion made and authenticated at IIIM Jammu [Table 1]. and controversy due to certain synonyms used for more than one or two drugs. Similar problem is faced by the plant Pushkarmool in Kerala. Throughout Kerala, the drug I. racemosa is widely Market study sold in the name of Pushkarmoolam, and there is another plant by the name Pushkarmulla in Malayalam language, the botanical Exclusive dependence on traders has created serious identity of this as per the botanist is Coffea travancorensis malpractice of adulteration and selling of substandard Wight and Arn syn. Psilanthus travamcorensis Wight and Arn. medicinal plant raw materials in the market. Hence, it belonging to Rubiaceae family.[1] is mandatory to study the market samples to check the adulteration. Six markets from all over India were selected In Bhavprakash Kustha is quoted as the substitute for these six markets are Kullu (H.P.), Amritsar, Jaipur, Kolkata, Pushkarmool along with Tagara, Langali, and Sthoneyka[2] Mumbai, and Kochi. Following points were kept in mind

Table 1: Date and place of genuine sample Plant name Date of collection Place of collection Herbarium account no. Inula racemosa 11‑09‑2012 Dist. Doda J&k 13697 Inula royleana 11‑09‑2012 Dist. Kathua J&k 5989 Saussurea lappa 11‑09‑2012 Dist. Doda J&k 17279

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S100 Nagar and Lamo: Pushkarmool a market study while a collection of market samples. Markets samples were grades were collected with the simple order method. Sample collected as such and not verified on the spot. All the available purchased or received from contacts were properly labeled, stored, and subjected to the investigation [Table 2]. Table 2: Date and source of market samples Kullu market Markets Date of purchasing or receiving Collector Kullu 18‑04‑2012 Scholar In the market of Kullu, the drug Pushkarmool is being sold under the name of Manoo and is sold at the rate Amritsar 05‑04‑2012 Scholar 150/- rupees per kg. Jaipur 05‑05‑2012 Scholar Kolkatta 10‑04‑2012 Contacts Amritsar market Mumbai 25‑04‑2012 Contacts In Amritsar market, the drug Pushkarmool is being sold under Kochin 20‑07‑2012 Contacts the name of Pokarmool and is sold at the rate of 190/- per kg.

Table 3: Summarized organoleptic features Source Appearance Size Colour Odor Taste Fracture Genuine Stout, hard, cylindrical, 5–14 cm long in Dark Khaki with khaki Characteristic and Bitter Short and carrot‑like at the upper end length and 2–3 cm color longitudinal camphoraceous uneven twisted and gradually tapering in thickness striations at the end rough, having some whitish colored lenticels, longitudinally wrinkled Kullu Stout, hard, cylindrical, 4–7 cm long Dark Khaki with khaki Characteristic and Bitter Short and carrot‑like at the upper end in length and color longitudinal camphoraceous uneven twisted and gradually tapering 0.5–1.5 cm in striations at the end rough, having thickness some whitish colored lenticels, longitudinally wrinkled Amritsar Stout, hard, cylindrical, 4–9 cm long in Dark Khaki with khaki Characteristic and Bitter Short and carrot‑like at the upper end length and 1–2 cm color longitudinal camphoraceous even twisted and gradually tapering in thickness striations at the end rough, having some whitish colored lenticels, longitudinally wrinkled Jaipur Stout, hard, cylindrical, 3–8 cm long in Dark Khaki with khaki Characteristic and Bitter Short and carrot‑like at the upper end length and 1–2 cm color longitudinal camphoraceous uneven twisted and gradually tapering in thickness striations at the end rough, having some whitish colored lenticels, longitudinally wrinkled Mumbai Stout, hard, cylindrical, 5–10 cm. long in Dark Khaki with khaki Characteristic and Bitter Short and carrot‑like at the upper end length and 2–5 cm color longitudinal camphoraceous uneven twisted and gradually tapering in thickness striations at the end rough, having some whitish colored lenticels, longitudinally wrinkled Kolkata Mixture of three or four types 3–4 cm long in Some pieces were Peculiar sweet Short of drugs. Small, straight, thin length and 1 cm saddle brown, smell and pieces in thickness and some were uneven Goldenrod Kochin Stout, hard, cylindrical, 5–11 cm long Dark Khaki Characteristic Bitter Short carrot‑like at the upper and 2–3 cm in with khaki color and and end twisted and gradually thickness longitudinal camphoraceous. uneven tapering at the end rough, striations having some whitish colored lenticels, longitudinally wrinkled

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Jaipur market grade material. More than 50% of the material was under matured roots with a thickness <1 cm. Sample from Mumbai In Jaipur market, the drug Pushkarmool is being sold under market consisted of big chunks of the upper part of roots of the name of Pushkarmool, and it costs 240/- rupees per kg. Pushkarmool.

Mumbai market In ancient days Vaidyas usually go to the forest to collect In Mumbai market, the drug Pushkarmool is being sold under medicinal plants and prepare the medicines by themselves. the name of Pushkarmool and is cost 800/- rupees per kg. Therefore, there was not much-documented information with regard to morphology and identification of medicinal Kolkata market plants in Ayurvedic texts. However, due to extensive industrialization and urbanization it has become almost In Kolkata market, the drug Pushkarmool is being sold under unpractical for an Ayurvedic physician to personally procure the name of Mool and is sold in this market at the rate of the authentic drugs and therefore totally dependent on raw 200/- per kg. drug sellers and the middlemen for procurement of medicinal plant raw materials. This exclusive dependence on traders Kochin market has created serious malpractice of adulteration and selling In Kochin market, the drug Pushkarmool is being sold of substandard medicinal plant raw materials in the market. under the name of Pushkaramoolam and is sold at a cost Hence, it is mandatory to study the market samples to check 210/- rupees per kg. the adulteration.

Summarized organoleptic features of genuine samples, as well as market samples, are given in Table 3. REFERENCES

1. Murthy KR. Bhavmishra. Bhavaprakasha. Vol. 1. DISCUSSION AND CONCLUSION Varanasi: Chaukhamba Krishnadas Academy; 2008. p. 142-3. The market samples of Pushkarmool were collected from 2. Jamna, Balakrishnan J, Ramakrishnan R, Sarala P, Jolly S. the markets of Kullu, Amritsar, Jaipur, Kolkata, Mumbai, Comparative pharmacognostic study of Inula racemosa and Kochin. After studying the samples collected from Hook. F and its adulterant Coffea travancorensis wight above-mentioned markets, it had been found that price of and arn. Indian J Nat Prod Res 2012;3:386-94 Pushkarmool varied from rupees 150 to 800, sample collected 3. Chunekar KC. Bhavmishra. Bhavprakasha Nighantu from all the above markets except Kolkata, is having the Commentary. Varanasi: Chaukambha Bharati Academy; similar characters and resemblance with the characters of root 2010. p. 91-2. of I. racemosa which is an authentic source of Pushkarmool. 4. Vaidya B . Some controversial drugs in Indian medicine. rd Hence, the sample collected consisted of an original sample 3 ed. Varanasi: Chaukhamba Orientalia; 2010. p. 37. of Pushkarmool. Sample from Kolkata market consisted of unidentified drug material with few pieces of satavari. Sample of Amritsar and Jaipur market was consisted of poor Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S102 Is refined oil safe for health?

Lamo Ringzin1*, Nagar Lalit2 1Department of Agadtantra, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India, 2Department of Dravyaguna, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

In this hurried lifestyle, every individual is working laboriously to refine himself even at the cost of their health, making his life barren. Person is so much occupied in his daily work that he hardly gets time to judge what he is eating. Most of the people depend on the packed and processed food. These food items contain a lot of preservatives, food additives, and added sugars which make these food items slow poisons and can be compared

REVIEW ARTICLE REVIEW with the garvisha. Garvisha as per Ayurveda is the type of toxin which comes from outside the body which includes environmental toxins such as chemicals, preservatives, air and water pollution, genetically engineered foods, synthetics and chemicals in clothing, synthetic drugs, chemicals in household cleansers etc. In a country like India where we produce more than hundred natural edible oils but these natural oils are hardly seen in modern kitchens and are superseded by refined vegetable oils without understanding the chemical process and hazards of eating these chemically processed refined vegetable oils. Thus, in the present review article author focuses on the process of refining and its hazards.

Key words: Garvisha, hazards, refined oil

INTRODUCTION chemicals in household cleansers, and heavy metals such as lead, arsenic and asbestos. Garvisha also includes toxins oday, we are enclosed by different types from spoiled foods. Food is the most important part of our of toxins, i.e., Visha, these toxins are health and presently the most ignored part. Food has been Tpresent everywhere such as impurities in given more importance in Ayurveda than medicines. Charak the air, water, and soil. Visha is the substance Samhita, the most authoritative text of Ayurveda says that which immediately after entering into the body both human and his/her diseases are outcome of his/her causes the vitiation of the healthy dhatus or food.[2] Ayurveda states that one must regularly take such killing of the healthy person is defined as Visha. foods which help in maintaining and promoting health and Visha causes sadness to the world.[1] Ayurveda which prevent diseases (Charak Sutra: 5/13).[3] has defined a lot of food items which have Rasayan properties and helps our body to fight In this hurried lifestyle, every individual is working laboriously against these impurities and toxins. However, to refine himself even at the cost of their health, making his nowaday’s most of the people depend on the life barren. Person is so much occupied in his daily work that packed and processed food. These food items he hardly gets time to judge what he is eating. For choosing contain a lot of preservatives, food additives, his food to eat, he depends on the commercials he saw, and to and added sugars which make these food items earn money, these food manufacturers dare to serve toxins and slow poisons and can be compared with the slow poison in the form of refined and processed food. Lot of garvisha. Garvisha as per Ayurveda is the type these packed and processed food are promoted by the major of toxin which comes from outside the body. doctor’s associations. Whereas our ancestors choose their Garvisha is the toxic combination of poisonous food according to the climate of the place, like in northern or non-poisonous substance.[1] Gara is a toxic and eastern India mustard seed oil is the conventionally used combination of poisonous or nonpoisonous substance and which exerts toxic effect Address for correspondence: after interval of some time and as such does Lamo Ringzin, Department of Agadtantra, not kill the patient instantly.[1] Included are Faculty of Ayurveda, Institute of Medical Sciences, environmental toxins such as chemicals, Banaras Hindu University, Varanasi, Uttar Pradesh, India. preservatives, poisons, air and water pollution, Phone: +91-9646170039. genetically engineered foods, synthetics E-mail: [email protected] and chemicals in clothing, synthetic drugs,

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S103 Ringzin and Lalit: Refined oil a curse kitchen oil, in southern India people used coconut oil whereas Water degumming is the process in which water is added to the in central India people mostly use peanut oil. We have also oil. After a certain reaction period hydrated phosphatides can seen in every debate we compare present lifestyle with our be separated either by decantation (settling) or continuously grandparents, we talk about how they live their life? What by means of centrifuges. In this process large amount of they eat? However, after all these debates, we forget all and water-soluble and even a small proportion of the non-water start with our present lifestyles. soluble phosphatides are removed. The extracted gums can be processed into lecithin for food, feed or for technical In a country like India where we produce more than hundred process. Neutralization is the process in which any free fatty natural edible oils but these natural oils are hardly seen in acids, phospholipids, pigments, and waxes in the extracted modern kitchens and are superseded by refined vegetable oils oil promote fat oxidation and leads to undesirable colors without understanding the chemical process and hazards of and odors in the final product. These impurities are removed eating these chemically processed refined vegetable oils. The by treating the oil with caustic soda (sodium hydroxide, an chemicals used for the refining of edible oils are hexane, sodium extremely corrosive base used to clean clogged kitchen sink hydroxide, sodium carbonates, and many more. In India, we drains) or soda ash (sodium carbonate). These impurities settle have thousand’s year’s old history of eating natural edible oils to the bottom and drawn off. The refined oils are light in color, such as mustard oil, peanut oil, coconut oil, and many others. less viscous and more susceptible to oxidation. Bleaching Whereas refined oils such as soy oil, safflower, and linseed is the removal of colored materials in the oil. The heated oils have a history of using it in paint and varnishes industry oil is treated with various bleaching agents such as fuller’s 50 years ago. Then, chemists learned how to make paint from earth, activated carbon, or activated clays. Many impurities petroleum, which was cheaper. As a result, the seed oil industry including chlorophyll and carotenoid pigments are absorbed had loads of crop that was hard to sell. They eventually were by the process and removed by filtration. However, bleaching given to farmers to make their pigs fatter with less food! The also promoted fat oxidation since some natural antioxidants crops that had gone from the paint industry ended up as food on and nutrients are removed along with the impurities. a farm for animals which, in turn, ends up on our plate as well.[4] Deodorization is the final step in the refining of vegetable oils. Pressurize steam at extremely high temperature (500° or more) is used to remove volatile compounds which would Process of Refining Edible Oils cause off odors and tastes in the final product. The oil produced is referred to as “refined oil” and is ready to be consumed or Refined vegetable oil starts from the seeds of various plant for the manufacture of other products. A light solution of citric sources. The fats from plant seeds are polyunsaturated, acid often added during this step to inactivate any metals such meaning they remain in a fluid state at room temperature. There as iron or copper present in the final product.[5] are many different kinds of commercially refined vegetable based oils, including canola or rapeseed oil, soybean oil, During these processes, some (0.5–1%) of the fatty acids canola oil, corn oil, sunflower oil, safflower oil, and peanut molecules are changed chemically into toxic molecules oil. The generic cooking term “vegetable oil” refers to a that interfere with normal biochemical interactions between blend of a variety of oils often based on palm, corn, soybean, molecule necessary for normal cell functions, thus interfering or sunflower oils. Refined cooking oils are made by highly with health. Furthermore, the process of refining vegetable intensive mechanical and chemical processes to extract the oil damages the fats and makes the oil very unstable and oil from the seeds. This process removes the natural nutrients prone to going rancid quite easily. Rancid oils in any form from the seeds and creates a final product which oxidizes are particularly bad for your health because they introduce easily. The oxidation factor makes these oils more likely to cancer-causing free radicals into your body, without the break down into cancer-causing free radicals within the body. benefit of including an antioxidant like Vitamin E. During the process of refining minor ingredients (phytochemicals) Oilseeds such as soybean are gathered are husked and that makeup about 2% of most cells but have major benefits cleaned of dirt and dust, then crushed. Crushed seeds are then on health are removed. It helps in lowering cholesterol heated to temperatures between 110 and 180° in a steam bath and blocks cholesterol absorption from foods, improves to start the oil extraction process. The seeds are put through cardiovascular function, improves digestion and stimulate a high volume press which uses high heat and friction to pancreatic enzyme production, improves liver and gallbladder press the oil from the seed pulp. The seed pulp and oil are function and increase bile flow, acts as anti-oxidants and then put through a hexane solvent bath and steamed again to stabilize essential fatty acids against oxidation (rancidity), squeeze out more oil. Now the seed oil mixture is put through acts as anti-inflammatory agents, protect visual function, and a centrifuge and phosphate is added to begin the separation of improves brain function. the oil and seed residues. After solvent extraction, the crude oil is separated, and the solvent evaporated and recovered. The seed pulp residues are conditioned and reprocess to Hazards of Refined Edible oil make by-products such as animal feed. The crude vegetable oil is then put through further refining techniques including In addition, many refined vegetable oils are also hydrogenated. degumming, neutralization, and bleaching. This hydrogenation process makes them solid at room

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S104 Ringzin and Lalit: Refined oil a curse temperature so they can be sold as margarine and shortening. CONCLUSION This hydrogenation process further damages the fatty acids in oils, creating trans fatty acids, which are particularly dangerous Try to avoid any refined oils. They are cheap, they are to human health. Trans fatty acids raise the level of lipo processed and they are downright dangerous to your proteins (a), the strongest known risk factor for cardiovascular health. Instead of it start using natural filtered oils which disease, decrease testosterone, increase abnormal sperm and are unprocessed, raw and does not contain any chemicals. interfere with pregnancy in animals, correlate with low birth Moreover, these natural oils are time tested on the parameters weight human babies, lower the quality of human breast of environmental and climate changes from thousand years milk, interfere with blood insulin function, interfere with in India. liver enzymes necessary for detoxification (the cytochrome P450 system), change the fluidity of cell membrane making tem harder, slow down their reactions, lower cell vitality and REFERENCES make cell membrane more permeable, make platelets more sticky, increase cholesterol, increase low-density lipoprotein 1. Shukla V, editor. Charak, Samhita Chikitsasthan, 23/4. [6] cholesterol, and lower high-density lipoprotein cholesterol. New Delhi: Choukhamba Sanskrit Pratishthan, Reprint; 2002. The consumption of vegetable oils created through chemical 2. Pandey PK. Agnivesha. Caraka Saṃhita. Varanasi: extraction processes is linked to widespread inflammation Chaukhambha Bharati Academy; Reprint-2013. p. 575. within the body, elevated blood triglycerides, and an impaired 3. Pandey PK. Agnivesha. Caraka Saṃhita. Varanasi: insulin response. These oils have been linked to diabetes, Chaukhambha Bharati Academy; Reprint; 2013. p. 107. [1] cancer and heart disease in multiple studies. Whereas the 4. Debi. Refined Oils and Why you Should Never Eat natural oils are filtered through strainers or others equipments Them. Available from: http://www.happilyunprocessed. to remove the solid particles and contaminants from the oil, but com/the-basics/refined-oils-and-why-you-should-never- no chemicals are used in the process. They are generally dark eat-them/. [Last cited on 2016 Nov 02]. and cloudy in appearance and have a peculiar seed smell from 5. Davis E. Vegetable Oil Processing. Available from: which they are extracted. Filtered natural oils are better than http://www.healthy-eating-politics.com/vegetable-oil. refined ones as they are less processed and treated hence have [Last cited on 2016 Nov 02]. a higher value of nutrients in them. Refined oils are devoid 6. Davis E. Refined Vegetable Oil. Available from: https:// of beta-carotene, Vitamin E, and minerals. Another benefit of www.ketogenic-diet-resource.com/vegetable-oil.html. using filtered oil is that since they have a strong aroma, they are [Last cited on 2016 Nov 02]. used in lesser amounts helping you manage weight and lipid levels better. They also contain a higher amount of vitamins and minerals which add to your overall nutrient intake. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S105 Herbs for textile dye–an eco-friendly approach

Manisha Soni Department of Rasa Shastra, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

Dyes derived from natural materials, such as plant leaves, roots, bark, insect secretions, and minerals, were the only dyes available to mankind for the coloring of textiles until the discovery of the first synthetic dye in 1856. Rapid research strides in synthetic chemistry supported by the industrialization of textile production not only

REVIEW ARTICLE REVIEW led to the development of synthetic alternatives to popular natural dyes but also to a number of synthetic dyes in various hues and colors that gradually pushed the natural dyes into oblivion. However, environmental issues in the production and application of synthetic dyes once again revived consumer interest in natural dyes during the last decades of the twentieth century. Textiles colored with natural dyes are preferred by environmentally conscious consumers, and today, there is a niche market for such textiles. However, the total share of natural dyes in the textile sector is approximately only 1% due to certain technical and sustainability issues involved in the production and application of these dyes such as non-availability in ready-to-use standard form, unsuitability for machine use, and limited and non-reproducible shades. Natural dyes are sustainable as they are renewable and biodegradable; however, they cannot fulfill the huge demand from the textile sector in view of the preferential use of land for food and feed purposes. In addition, overexploitation of natural resources to obtain dyes may result in deforestation and threaten endangered species. For these reasons, the global organic textiles standard permits the use of safe synthetic dyes and prohibits the use of natural dyes from endangered species. Various research efforts have been undertaken all over the world to address the shortcomings of natural dyes given the tremendous environmental advantage they offer. An aspect of the return to use natural dyes is the search for novel natural dyes from various plant materials. This is because the use of synthetic dye has recently been banned not only due to the carcinogenic nature of the intermediates used in the preparation of these dyes but also the effluent coming from their industries are the major cause of environmental pollution. There are several plants parts that provide natural dyes which might be used in the textile industry.

Key words: Dyes, industrialization, natural, organic, synthetic, textiles

INTRODUCTION efforts in the field of synthetic dyes and rapid industrialization of textile production resulted in almost complete replacement he art of dying is as old as our civilization. of natural dyes by synthetic dyes on account of their easy Dyed textile remnants found during availability in ready-to-apply form, simple application process, Tarchaeological excavations at different consistency of shades, and better fastness properties. The places worldwide provide evidence to the tradition of using natural dyes could survive only in certain practice of dying in ancient civilizations. Natural isolated pockets. Recent environmental awareness has again dyes were used only for coloring of textiles from revived interest in natural dyes mainly among environmentally ancient times till the nineteenth century. As the conscious people. Natural dyes are considered eco-friendly name suggests, natural dyes are derived from as these are renewable and biodegradable; are skin friendly natural resources. Coloring materials obtained and may also provide health benefits to the wearer. Natural from natural resources of plant, animal, mineral, and microbial origins were used for coloration Address for correspondence: of various textile materials. Different regions of Manisha Soni, Department of Rasa Shastra, the world had their own natural dying traditions Faculty of Ayurveda, Institute of Medical Sciences, utilizing the natural resources available in that Banaras Hindu University, Varanasi - 221 005, Uttar region. Use of natural dyes started to decline after Pradesh, India. Phone: +91-8299330578. the invention of synthetic dyes in the second half E-mail: [email protected] of the nineteenth century. Concerted research

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S106 Soni: A review on natural herbs used in textile dye dyes can be used for dying almost all types of natural fibers. as that will damage the fabric structure. In such cases, it is Recent research shows that they can also be used to dye advisable to have a MLR of at least 1:100 so that the fabric some synthetic fibers. Apart from their application in textiles, is completely immersed in the dye liquor during dying and natural dyes are also used in the coloration of food, medicines, dying is uniform. If simultaneous mordanting is to be carried handicraft items and toys, and in leather processing, and many out, the required quantity of mordant is also added to the dye of the dye-yielding plants are used as medicines in various bath. After the dying is over, the dyed materials are removed traditional medicinal systems. There are several challenges and allowed to cool down a little and then washed with and limitations associated with the use of natural dyes. The water. Some traditional dyers leave the material in the dye current dyestuff requirement from the industry is about 3 bath itself to cool and then remove the material for washing. million tones. Considering this fact, the use of natural dyes in The washed dyed material is then soaped with a hot soap mainstream textile processing is a big challenge. As agricultural or nonionic detergent solution to remove loosely held dye land is primarily required to feed an ever-increasing world and is again rinsed with water and air-dried in the shade. At population and support livestock and biodiversity should not industrial scale, hydroextractors are used to remove excess be compromised for the extraction of dyes, sustainability of water during washing. If post-mordanting is to be carried out, natural dyes is a major issue.[1] This paper discusses various the washed material is taken up for post-mordanting without issues related to the use of natural dyes in textiles such as soaping and soaping is carried out on the post-mordanted potential sources, advantages and disadvantages, methods, material after washing. When cotton materials are dyed with application methods, and sustainability issues (Table 1). dyes such as madder which do not have affinity to it without mordants, the premordanted dyed material may be further post-mordanted to get different shades and improvements in DYING fastness properties. Treatment with small amounts of copper mordant improves the fastness to light for many dyes although As for synthetic dyes, the amount of dye to be taken is it also results in slight hue changes. Such treatment with normally given as % shade. It denotes the amount of dye (in copper to improve lightfastness was also practiced earlier for grams) to be taken for dying 100 g of textile material. The certain synthetic dyes. A post-dying treatment with tannins terminology remains the same for both crude dye material and and alum can help in improving the fastness to washing. purified extracts. As the dye content of raw materials is low, it is common to use 10–30% shade whereas the amount can be reduced to 2–5% for the purified dye extracts. The amount Categories of Textile Suitable for Dying with of mordants is also selected in relation to the shade dyed. Natural Dyes A larger quantity of mordants is needed for higher shades. As is the case with synthetic dyes, the amount of water to be Natural dyes can be used on most types of materials or fibers; taken in the dye bath is an important parameter. In technical however, the level of success regarding fastness and clarity terms, it is given in the recipe as the material-to-liquor ratio of colors varies considerably. Users of natural dyes; however, (MLR). The MLR denotes the amount of water in ml required tend to also use natural fibers, and so much emphasis will per gram of the fabric to be dyed. As natural dyes differ in be given to this group. Natural fibers come mainly from their chemical constituents, their dying procedures also differ; two distinct origins, animal origin, or vegetable origin. however, their basic dying process is similar. There may Fibers from an animal origin include wool, silk, mohair and be different optimum temperature, time, and pH of dying; alpaca, as well as some others which are less well known. however, the basic steps remain the same. Many natural All animal fibers are based on protein. Natural dyes have a dyes are dyed at near boiling temperature on cotton. Wool strong affinity to fibers of animal origin especially wool, silk, and silk are dyed at a lower temperature although some dyes and mohair and the result with these fires are usually good. may dye cotton also at lower temperature. Most dyes require Fibers of plant origin include cotton flax or linen, ramie, jute neutral pH but some dyes require acidic pH and some may hemp, and many others plant fibers have cellulose as their need alkaline pH. For dying animal fibers wool, Pashmina, basic ingredient. Natural dying of certain plant-based textile and silk, generally 1–2% of acetic acid is added during can be less successful than their animal equivalent. Different dying. The material to be dyed premordanted or otherwise mordanting techniques are called for with each category. is introduced into the dying bath at room temperature, and When a blend of fiber of both animal and plant origin is being the temperature is then increased slowly to ensure uniformity dyed, then a recipe should be chosen which will accentuate of dying. The material is usually dyed for at least an hour to the fibre which is required to be dominant. allow the dye to penetrate well inside the textile material. The movement of textile material in the dye bath is very essential. Advantages of Natural Dyes If the dying is carried out in dying machines, movement of the material is taken care of but in hand dying, the fabric Eco-friendly needs to be continuously stirred in the dye bath, otherwise uneven dying may result. If delicate fabrics such as pashmina Natural dyes are considered to be eco-friendly as these are are to be dyed, the dye bath should not be stirred continuously obtained from renewable resources as compared to synthetic

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S107 Soni: A review on natural herbs used in textile dye dyes which are derived from non- renewable petroleum that extracts of tannin-rich pomegranate rind showed strong resources. These are biodegradable and the residual vegetal absorption in UV region and cotton fabrics treated with these matter left after extraction of dyes can be easily composted extracts showed excellent UV protection which was durable to and used as fertilizer. They produce soft colors soothing to washing. As cotton and other cellulosic are frequently treated the eye which are in harmony with nature. with tannins in the mordanting step during dying with natural dyes, it is likely that such dyed fabrics would also show good Antibacterial and antimicrobial properties UV protection. Ibrahim et al.[10] have reported improvements in both UV protection and antibacterial activity for polyamide In addition to these environmental benefits, natural dyes six fabrics after treatment with natural dyes. also offer functional benefits to the wearer and users of such textiles. Fabrics dyed with some natural dyes have been Curative and medicinal properties reported by the wearers to be free of odor perhaps due to the antibacterial or bacteriostatic properties of natural dye In the Table no. 1 many natural dyes, such as myrobolon fruits, materials. Users of natural dyed fabrics have also found turmeric, manjistha root, Arjuna (Terminalia arjuna) bark, and such fabrics to be mosquito repellent and/or moth repellent safflower florets, among others possess curative properties as perhaps the plant material from which these dyes and have been used in various traditional medicinal systems. were derived might also have contained natural repellent Textiles dyed with these materials may also possess healing substances. In addition, recently, cellulosic textiles treated properties by absorption of medicinal compounds through with natural plant extract have been found to exhibit flame- the skin. Textiles produced in Kerala, India, by dying with retardant properties.[2] Many of the natural dye materials herbs as per the traditional Ayurvedic system of medicine and possess. Therefore, textiles dyed with such materials are also known as “Ayurvastra” have become very popular as health likely to show antimicrobial properties, and the same has and well-being textiles and also as medicinal or curative been reported by many researchers.[3-5] textiles and are being exported to various countries. Various companies are now marketing naturally dyed textiles as Ultraviolet (UV) protection health and well- being textiles. Many of the natural dyes absorb in the region and therefore fabrics dyed with such dyes should offer good protection Drawbacks of Natural Dyes from UV light. Improvement in UV characteristics of natural cellulosic fibers after treatment with natural dyes has been Natural dyes are considered to be an eco-friendly alternative reported by various researchers.[6-8] Gupta et al.[4] observed for dying of textile materials, especially natural fiber textiles. that treatment with tannins during mordanting itself improved However, there are many limitations in the usage of natural the UV protection of fabrics. Saxena et al.[9] also observed dyes some of which are listed below.

Table 1: Some promising natural dye sources[1] Common name of the plant Botanical name Part used Color obtained Siam weeds Eupatorium odoratum Whole plant Yellow Goat weed Ageratum conyzoides Whole plant Yellow Jack fruit tree Artocarpus heterophyllus Bark Yellow Gulmohar Delonix regia Flower Olive green Teak Tectona grandis Leaves Yellow Babool Acacia nilotica Leaves, bark Yellow/brown Water lilly Nymphaea alba Rhizomes Blue Dahlia Dahlia variabilis Flowers Orange Amla Emblica officinalis Bark, fruit Grey 10 Indian Jujube Ber Ziziphus mauritiana Leaf Pink Drumstick Moringa pterygosperma Leaf Yellow Sausage tree Kigelia pinnata Petals, heartwood, bark Yellow, pink African tulip tree Spathodea companulata Flower Yellow/orange Tamarind Tamarindus indica Leaves, seeds Yellow, brown Golden dock Rumex maritmus Seeds Brown Eucalyptus Eucalyptus camaldulensis Bark Yellow and brown Red sandalwood Pterocarpus santalinus Wood Red

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S108 Soni: A review on natural herbs used in textile dye

Tedious application process Fastness properties Natural dyes require a longer dying time in comparison Colorfastness to light and washing are most important with synthetic dyes as very often an additional mordanting parameters to evaluate the performance of a textile and step is required. Use of raw dye-bearing materials ensures deciding about its end use although colorfastness to rubbing authenticity; however, at the same time, involves additional and perspiration are also important especially if it is to be dye extraction steps that require time and separate setup. used as apparel. A material should have good fastness to Natural dyes in this form are also not suitable for use in many light if it is to be used for making curtains although a little commercial textile dying machines which makes the process lower fastness to washing may be satisfactory for this labor intensive. In addition, in an industrial setup, disposal application. Colorfastness properties of natural dyes are a of solid residual biomass is problematic. Purified extracts, cause of concern. Only a few natural dyes possess fastness although suitable for machine application, are costly and not properties conforming to modern textile requirements. economical. Logistics for making agricultural by-products Restrictions on the use of certain metal salts for mordanting such as pomegranate rind, onion skins, or fruits and leaves such as chromium, copper, tin, and so on by eco standards of trees from the forests available for dying purposes are has not only reduced the color gamut of natural dyes but has not in place which would have helped in reducing the costs. also made the task of producing shades with good fastness Exhaustion of most of the natural dyes on textile materials is properties difficult. Improper application procedures used poor in spite of using the mordants which leaves a large quantity by certain practitioners of natural dyes are also sometimes in the dye bath after dying. That increases the cost of dying responsible for poor fastness properties. Improvements and although it may not have other environmental implications optimization of mordanting and dying procedures can help as seen for synthetic dyes due to the biodegradable nature of in solving this issue. Exploring the new sources for dyes these dyes. Traditional dyers reused the dye bath; however, can increase the number of dyes with better colorfastness the color obtained is different from the earlier lot which may properties. not be acceptable by today’s standards. All these increase the cost of naturally dyed textiles. Safety issues Exploration of new sources for dyes can certainly help in Limited shade range increasing the shade range of natural dyes with good fastness Shade range of natural dyes is limited. Out of the three properties. However, extensive research on the safety of these primary colors red, yellow, and blue, although there are materials to humans and the environment would be needed several sources for red and yellow dyes, there is only one before propagating their usage as everything of natural origin major source of the blue dye: Indigo. As natural dyes differ may not be safe. Nature is known to produce poisonous in their application process, only few dyes can be applied in substances also; therefore, thorough toxicological evaluations mixtures and differences in fastness properties further limit for the new sources are necessary. Use of metallic mordants the choice. Even a common secondary color such as green also requires caution so as not to cause adverse health effects needs to be produced by over dying as blue dye indigo being during handling. Precautions should also be taken to prevent a vat dye has an entirely different application process that pollution problems in the usage of these mordants and it increases the dying time and cost.[11] should be ensured that the amount of restricted mordant in the dyed textile is within the limits set by eco regulations. Nonreproducible shades Characterization and certification issues Difficulty in reproducing the shades is another major drawback of natural dyes which is caused by the inherent Although dying of textile fabrics with dyes obtained from variations in the proportion of chemical constituents in the various natural resources has been extensively investigated, natural material and thus in its crude extract depending on little information is available on the identification and the maturity, variety, and agro-climatic variations such as soil characterization of the natural dyes. Natural dyes, being type, region, and so on. Therefore, it is not possible to produce plant metabolites, are present only in small amounts in dye- the same shade with a particular natural dye in every dying bearing materials along with large quantities of other non-dye operation.[12] The production of standardized dye powders is materials. The dye content may vary according to the age, part an expensive and complicated exercise as most of the natural of the plant, and agro-climatic conditions, and it is important dyes contain various chemical constituents. Some of the to know the dye content in order to get reproducible shades. natural dyes are pH sensitive and tend to change color due to While procuring the dye materials, pricing should match the change in pH. As natural dyes tend to form colored complexes dye content and when powdered dye materials or extracts are with metal ions, the mineral composition of water may also used, these should be authentic. Thus, determination of dye cause shade variations. Hence, even the same standardized content as well as characterization of dye material is important powder may give different shades at two different places in the case of natural dyes. Absorption spectroscopy is very due to the differences in mineral content and pH of the water successfully used for measuring the dye content of synthetic which makes it very difficult to reproduce the shades. dyes but has limited applicability for natural dyes as these

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S109 Soni: A review on natural herbs used in textile dye dyes are usually not a single chemical entity but a mixture the textile industry. It has still not become possible mainly of closely related compounds, and in many cases, there are due to the essential two dependent factors (dye & mordant) no clearly defined absorption maxima. A literature survey and color development mechanism of natural colors applied shows that the earliest attempts to characterize the natural to textiles. In countriessuch as India, Nigeria, Liberia, and dyes were made in the context of identifying the dyes present Uganda among others, there is a wealth of plants available for on historical textiles kept in museums or those found in producing natural dyes that could be utilized for commercial archaeological excavations. Different techniques including dying of textiles. Therefore, much more research and high-performance liquid chromatography, thin-layer developmental efforts should be geared toward producing chromatography (TLC), high-performance TLC (HPTLC), high quality natural dyes with shades comparable to some of UV visible, and mass spectroscopy have been employed for the highly rated synthetic dyes. this purpose.[13,14] However, there are no certification bodies or any testing agencies that can certify or characterize and identify the commercial natural dyes or the fabrics dyed with REFERENCES natural dyes although such fabrics fetch higher prices. As a result, some unscrupulous elements in the trade tend to mix 1. Saxena S, Raja AS. Natural dyes: Sources, chemistry, natural dyes with cheap synthetic dyes or try to pass off the application and sustainability Issues. Roadmap Sustain fabrics dyed with synthetic dyes as those dyed with natural Text Clothing 2014;45:37-80. dyes. It is quite common to find people trying to market 2. Basak S, Samanta KK, Arputhraj A, Saxena S, fabrics dyed with synthetic alizarin or indigo as dyed with Mahangade R, Narkar R. Method of Dyeing and natural dyes. Therefore, development of process protocols Protective finishing of Cotton Textiles using Vegetable for quick identification and characterization of natural dyes Extract. Indian Patent Application no 3469/MUM/2012; is very important for the sustainability of true natural dyed 2012. textiles. TLC and HPTLC techniques can be easily employed 3. Datta S, Uddin MA, Afreen KS, Akter S, for quick identification of natural dyes by comparing with Bandyopadhyay A. Assessment of antimicrobial chromatographic fingerprints of authentic natural dye effectiveness of natural dyed fabrics. Bangladesh J Sci samples. Ind Res 2013;48:179-84. 4. Gupta D, Khare SK, Laha A. Antimicrobial properties of natural dyes against gram–negative bacteria. Color CONCLUSION Technol 2004;120:167-71. 5. Prabhu KH, Teli MD. Eco-dyeing using Tamarindus It has been found that lots of natural materials such as indica L. seed coat tannin as a natural mordant for leaves, roots, bark, insect secretions, and minerals are used textiles with antibacterial activity. J Saudi Chem Soc for natural dying. There are lots of natural products still 2011. DOI: 10. 1016/j.jscs.2011.10.014. untouched. There are lots of unharnessed natural products and 6. Chattopadhyay SN, Pan NC, Roy AK, Saxena S, required scientific studies and systematic reports on dying of Khan BA. Development of natural dyed jute fabric with textile with eco-friendly natural dyes are still insufficient. improved color yield and UV protection characteristics. Though natural coloration is known from ancient time J Text Inst 2013;104:808-18. as artisanal practice for handicrafts, paintings, handloom 7. Katarzyna SP, Kowalinski J. Light Fastness Properties textiles, the chemistry of interaction of such colorants with and UV Protection Factor of Naturally Dyed Linen, Hemp textile materials is of relatively recent interest for producing and Silk. In: Proceedings, flaxbast 2008: International eco-friendly textiles. The present excessive use of synthetic Conference on flax and other Bast PLANTS, Saskatoon, dyes, estimated at around 10,000,000 tons per annum, the Canada. 2008. p. 21-3. production and application of which release vast amount of 8. Grifoni D, Zipoli G, Albanese L, Sabatini F. The role waste and unfixed colorant causing serious health hazard of natural dyes in the UV protection of fabrics made of and disturbing the eco-balance of nature is of great concern. vegetable fibers. Dyes Pigm 2011;91:279-85. Nowadays, fortunately, there is increasing awareness among 9. Saxena S, Basak S, Mahangade RR. Eco-Friendly people towards the use of eco-friendly natural dyes owing Durable Ultraviolet Protective finishing of Cotton to their better biodegradability and higher compatibility with Textiles Using Pomegranate Rinds. Paper Presented the environment. They are non-toxic, non-allergic to skin, at the International Conference on Advances Fiinbers, non-carcinogenic, abundant, and renewable. Thus, there are Finishes, Technical Textiles and Nonwovens, AATCC, needs of many more active researches to build knowledge Mumbai; 2013. p. 1-2. base and database with production of appropriate shades 10. Ibrahim AN, El-Zairy WM, El-Zairy MR, Ghazal HA. cards for different textiles. It will help to popularize the use Enhancing the UV-protection and antibacterial properties of natural dyes by solving some of its problems relative to of Polyamide-6 fabric by natural dyeing. Text Light Indl application methods, reproducibility and colorfastness. Sci Technol (TLIST) 2013;2:36-41. Improving the computerized color matching for use of 11. Sarkar AK. An evaluation of UV protection imparted synthetic dyes has now become regular practice in most of by cotton fabrics dyed with natural colorants. BMC

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Dermatol 2004;4:15. 14. Deveoglu O, Torgan E, Karadag R. High-performance 12. Sharma KK, Pareek PK, Raja AS, Temani P, Ajay liquid chromatography of some natural dyes: Analysis K, Shakyawar DB, et al. Extraction of natural dye of plant extracts and dyed textiles. Color Technol from Kigelia pinnata and its application on pashmina 2012;128:133-8. (cashmere) fabric. Res J Text Apparel 2013;17:28-32. 13. Samanta AK, Agarwal P. Application of natural dyes in textiles. Ind J Fib Text Res 2009;34:384-99. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S111 Critical review on the concept of Kajjali: The boon of Ayurvedic Herbomineral preparations (Rasaushadhi)

Namrata Joshi, Manoj Kumar Dash, Pradeep Kumar Panda 1Department of Rasashastra, Faculty of Ayurveda, Institute of Medical Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India, 2Department of Rasashastra and Bhaishajya Kalpana, Government Ayurved College, Raipur, Chhattisgarh, India, 3Department of Vikriti Vigyana, Government Ayurved College, Bolangir, Odisha, India

Abstract REVIEW ARTICLE REVIEW Rasashastra is the branch of Indian alchemy which manages the scientific utilization of purified and processed metals, minerals, valuable stones, marine, narcotic, and different herbs for curing diseases and rejuvenation. Kajjali Kalpa is a novel concept of ancient Indian drug delivery system. Despite the fact that the specialists of Rasashastra consider Kupipakwa Rasayana and Pottali Rasayana as prominent therapeutic agent, the Kajjali Kalpa - Khalviya Rasayana are likewise similarly effective Rasa yoga helpful in various clinical conditions. Black sulfide of mercury (Kajjali) comprehensively and synergistically acts with the herbal ingredients to bring multitargeted organ effect, in particular, Rasayana effects in its complete sense.

Key words: Gandhaka, Jarana, Kajjali, Kajjali Kalpa, Murchana, Parada, Rasashastra

INTRODUCTION of its longer stay and coordinated and sustain release, GI adsorption/stimulant, and even neurochemical irritability.[8] yurveda is a well-documented It also suppresses autoimmune reaction, drug reactions, and traditional system of Indian Medicine. hepatic abnormal metabolism. For formulations containing Rasa Shastra, a branch of Ayurveda pure mercury and pure sulfur in equal proportion, Sama A guna Kajjali (Mercury:sulfur 1:1) may be used. Similarly, in popular from medieval period, with twin aim, the foremost being the therapeutic applicability formulation where only mercury is prescribed, Rasasindoora of metals and minerals, i.e., Dehavaada[1] and may be added in place of mercury. Formulation in which another been the conversion of lower metals sulfur is more in comparison to mercury, Kajjali is to be into higher metals, i.e., Dhatuvaad.[2] Mercury prepared with additional sulfur and if mercury is more vice (Parada) is the prime member and considered versa may be used.[9] The information available in different to be highly auspicious material followed databases on Kajjali have been gathered and critically by sulfur (Gandhaka), which is essential to reviewed. The compiled information has been efficiently potentiate the therapeutic properties of former studied and classified in different headings and commented. in many ways. Kajjali is the name given to a compound obtained by either combination of Murchana and Jarana mercury and sulfur in different ratios[3] or even combination of these two along with some Jarana and Murchana are two independent procedures other metals.[4] In fact, Kajjali is considered to followed in Parada Sanskar (potentiation of mercury). be first Murchana of Parada.[5,6] Hundreds of Murchana involves change in physical state of mercury formulations are explained in classical texts from liquid to powder state. Murchana is a process in with the permutation combination of Kajjali[7] in different proportion of sulfur and mercury Address for correspondence: along with herbal ingredients. Kajjali kalpa is Namrata Joshi, Department of Rasashastra, Faculty of found effective in diseases of all Srotasa. The Ayurveda, Institute of Medical Science, Banaras Hindu impact might be multidimensional, free radicals University, Varanasi, Uttar Pradesh, India. scavenging, antioxidant, antimicrobial, reactant, Phone: +91-9319037367. proenzymatic, or immunomodulator. Kajjali E-mail: [email protected] complex is additionally more effective in light

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S112 Joshi, et al.: Critical review on the concept of Kajjali which mercurial compounds develop Avyabhicarita synonym for mercury) that should completely be digested Vyadhighatakatva (disease curing ) property or potency.[10] in Rasa, just like a food in human beings immediately after The basic concept behind is that mercury with or without ingestion of food the weight may be found increased, but sulfur converts in such a suitable compound form which after the digestion, the weight is not found increase. The could be used internally in the body for curing diseases even chemistry of mercury shows that it has affinity to assimilate without being reduced/converted to ashes. Murchana, which most of the metals to form amalgam. Perhaps, the text means to introduce disease-curing properties in Parada.[11,12] Ayurveda prakash describes it in a non-scientific language as Through this process, mercury and mercurial compounds the capacity of mercury (Parada) to dissolves all metals.[21] should develop a definite diseases curing capacity and The word Jarana denotes the textual meaning of digestion of after Murchana mercury may not return to its original form sulfur in mercury as well as the digestion of different metals (purvavastha). One specific type of Murchana in which in mercury. The former Jarana includes Bali (synonym for without heat treatment mercury is processed with sulfur is Gandhaka) Jarana (Samguna to Shadguna, i.e. 1:1 to 1:6) [13] Kajjali (Sagandha Niragni Murchana). Here, continues while the later includes 13th Samskara of Parada. The term and vigorous grinding is done until black-colored powder Jarana is also included for incineration in the context of Puti like compound is prepared that fulfills some typical tests louha. In the context of Parada, Gandhaka Jarana process such as absence of shininess and floating over water surface. ultimately converts Parada into a compound which is useful [14] As it is first Murchana of Parada, it is being used as a for therapeutic purposes, whereas Jarana as 13th Samskara primary component of even processing of mercury with takes Parada a potent Rasayana in respect of therapeutics and sulfur with heat treatment (Sagandha Agni Murchana) such thermostable (Pakkshacchhinna) for therapeutic as well as as Kupipakwa Rasayana, Parpati Kalpa, and Pottali kalpa. alchemical purposes. In Jarana, it may be that some changes in atomic structure which cannot be explained scientifically. Whereas such a change is not expected in Jarana Sanskar Among Astadasha Parada Samskara, i.e., processes for with the help of Vida and through various pharmaceutical potentiation of mercury, the Grasamana, Charana, Garbha procedures carried out using variety of instruments such as druti, and Bahya druti are meant only for Jarana of mercury, Baluka yantra, Kacchapa yantra, and Jarana yantra, the i.e., to assimilate extra appetite in mercury. process of digesting other metals and minerals in mercury is called as Jarana[15] percent of therapeutic strength in mercury can be obtained only after digestion (Jarana) of purified Kajjali sulfur (Suddha Gandhaka) in and it is different ratios. The digestion (Jarana) of mercury in sulfur (Gandhaka in Kajjali (black sulfide of mercury) is a preparation which is Parada) ranges from 1:1 ratio to 1:6 ratio; i.e., one part of made either triturating Parada (mercury) with Gandhaka mercury with either 1, 2, 3, 4, 5, or 6 times of purified sulfur. (sulfur) alone in different proportions[3] or Parada (Mercury) As per Ayurveda prakash in certain context, both the terms with Gandhaka (Sulphur) along with other metals and are used as synonyms[16] also otherwise both are different minerals[4] without using any liquid and is converted into from each other, only in the context of Gandhaka Jarana very soft powder, just like collyrium. The Kajjali when both are used as synonyms and for same objective. Even used properly along with other metals or herbs can cure all though mercury is a toxic element, the forms of mercury the diseases, pacify all the three humors (Tridodhahara), play an important role in converting it to toxic metal. In increases Shukradhatu (Vrishya), immediately spreads in Jarana, mercury does not convert in any form rather remain the body when consumed, clears the obstructed channels in its original (mercury) form. It consumes and digests some at the diseased organ, and enhances the properties of other metal contents of some minerals (Satva) and gold silver, etc., metallic or herbal medication when taken along with proper metals (Bija) in specified amount and returns to its original Anupana.[22,23] form (Purva avastha).[17] In Jarana, mercury does not essentially acquire disease-curing property rather it is done to prepare mercury suitable for further Samskara means for The Effects of Gandhaka Jarana in Different transformation purposes (Dhatuvada).[18] The process Jarana Proportions is also aimed at improving the appetite of mercury through various pharmaceutical procedures. By addition of Vida,[19] Sulfur can be added to mercury either in equal quantity, the hunger of mercury increases to many folds. Only then, it i.e., 1:1 or half quantity (1:1/2) or even in* ratio as 2, 3, 4, becomes efficient enough to digest the metals such as gold 5, 6 parts, and so on, i.e., in various proportions. Samaguna (Swarna), silver (Rajata), and mica (Abhraka). More the ratio Gandhaka Jarana (equal part), Dviguna (double), Shadaguna of sulfur digested in mercury better will be its therapeutic (6 times), Ashtaguna (8 times), dwadasha guna (12 times), strength and wider will be its therapeutic application. The Shataguna (100 times), and Sahasraguna (1000 times) are mercury digested with 6 times of purified sulfur (Shuddha therapeutically superior in increasing order of Jarana.[24] Gandhaka) not only gains therapeutic potency but also exhibits the rejuvenation properties.[20] The term Jarana Hence, according to Ayurveda, more the sulfur content safer is used which means whatever is added to Rasa (Rasa is and effective is the mercurial medicine.

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Quantity of Effects produced Effects produced as toxicity from Kajjali formulations are very negligible or nil sulfur as per Rasendra per Rasa Tarangini[26] since long time these medicines are being used in traditional Chintamani[25] systems of medicine. Moreover, the methodology adopted in Samaguna 100 times more Cures only the processing of mercury is so unique that it is treated with potent than common ailments materials that reduce toxicity of the same. For example, in purified Mercury Ayurveda for purification (Shodhana) of mercury, Allium (Shodhita Parada) sativum (Rasona) is used. For almost all procedures of Dwiguna Cures all types Cures Maha roga mercurial processing, sour gruel (Kanji) is used, such as of skin diseases heating, boiling in liquid bath, grinding, sublimation, and (Kusthahara) distillation.[29] Rasona and Kanji both contain sulfur that [30] Triguna Cures all types Cures phthisis (Kshaya reduces toxicity of mercury. Mercury whether it is purified of sharira jadata roga), Enhances extracted from Cinnabar (Hingulottha) or subjected for 8-fold (Sarva Jadya potency (Punsatva of process/Samskar (Ashta samskartita), it is not going to Vinashana) prakashana) have the complete therapeutic potency in it without [21] Chaturguna Cures wrinkles in Improves enthusiasm undergoing Murchana. Standardized the administered the skin (Vali) and (Utsaha), Intellect form of mercury as HgS, one of the least soluble substances. greying of hair (Medha), and Memory The KSP of HgS is 1 × 10–54|. Thus, the quantum of mercury (Palita) power (Smriti) ions that would be available on the administration of mercury Panchaguna Cures phthisis Cures all types of as sulfide can be much below the threshold of toxic limit. (Kshaya roga) chronic ailments However, HgS may be more soluble in the GI tract due to the Shadaguna Sarvarogahara Brings extraordinary action of digestive enzymes, changing pH conditions, and [28] (cures all types of powers complexation with other biomolecules present in the food. diseases) In another study related to immobilization and disposal of mercury, detailed observations on the process of mixing mercury and sulfur have been reported, using X-ray DISCUSSION diffraction and electron microscopy, as a function of grinding time. The grinding process slowly forms metacinnabar (black Kajjali is the base material and is used in maximum HgS) and up to 60 min of grinding, globules of mercury formulations of Indian system of medicine. It is more could be found to be present, using electron microscopy. common and popular in day-to-day practice as it is very easy After 90 min, free mercury could not be found, but the most to prepare and very safe to use. When used internally, it does important observation is the formation of particles containing not produce any toxic effects in the body. Organic mercury 2–15 weight% of mercuric oxide after 120 min of grinding. It such as methyl mercury and ethyl mercury is found to be is also found that the HgS particles are surrounded by sulfur 5000 times more toxic than inorganic mercury like sulfides particles.[31] Rasasindura that contains Kajjali has been of mercury.[27] Only minimum amount of mercury is absorbed trialed and was found to be non-toxic under therapeutic from inorganic mercury.[21] doses.[32] Yogavaahitva an unique attribute of mercury[33] substances possessing “Yogvavaahi” characteristics when Mercury is widely used in Ayurvedic drugs in the form of combined with others besides maintaining their own activity, mercuric sulfide (HgS), an inorganic compound of mercury. increase the therapeutic activity of the other substance many Rarely, other inorganic compounds of mercury such as folds. This is one of the reasons why the dose of the drug and mercuric chloride are used. Such use is restricted and always time required for the onset of action is considerably reduced advocated with a specific caution regarding its toxicity. It is a by mercurial compound.[34] Thus, mercury enhanced the well-known fact that negligible amount of sulfide compounds bioavailability of the drug. Kajjali has excess sulfur and is of mercury is absorbed through gastrointestinal (GI) tract and reported to contain free sulfur, trapped in the crystal lattice of hence is non-toxic in nature. The ancients brilliantly overcame HgS. Sulfur is a very important nutrient and many the problem of mercury toxicity by severely reducing its biomolecules such as methionine, cysteine, cystine, taurine, bioavailability through the use of sulfur. Intimate mixing of and antioxidant enzymes such as glutathione and many more, purified mercury and sulfur to prepare the Kajjali is the first contain sulfur. Kajjali containing medicines may induce the step in the preparation of any herbomineral preparations (excess) synthesis of these sulfur-containing biomolecules in (Rasaushadhi). As mentioned before, the compound of human systems. Antioxidants are the cell protectors against mercury and sulfur is prepared in many ways, but one always free radical-induced cell damage, and it is quite possible that finds the use of excess sulfur in the preparation of a form the rejuvenating effects and the reversal of aging effects. The called Kajjali, more than required for the stoichiometric antioxidants themselves could be the curative agents while preparation of HgS (approximately sulfur at 1/6 of the weight mercury could serve as a transient catalyst.[35,36] According to of mercury). The idea behind use of higher ratios of sulfur in Rasa tarangini, Kajjali can be used with different herbs to get the preparation of Kajjali. could be to prevent oxidation as optimum result. The paste prepared in milk of Calotropis well as to make available more sulfur.[28] Thus, chances of procera (Arka) using equal proportion of Kajjali and

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Saindhava lavana, is useful for cervical lymphadenitis/ better observed. Effective dose of active drug when consumed Scrofula or (Gandamala).[37] For Malaria (Sannipatika will be gradually released, adsorbed, and later on acts as per Jwara), Kajjali mixed with purified As2S3 (Shuddha the requirement at target cell. At the point when the plasma Haratala) along with Piper nigrum (Maricha) and Aconitum concentration of effective drug decreases, quickening of ferox (Vatsanabha)[38] or with Tamra bhasma triturated in active drug happens through biofeed system. In between juice of Azadirachta indica (Nimba swarasa)[39] may be used. these two phases, the inert drug - Kajjali will be slowly With cuttlefish bone (Samudraphena),[40] it is prescribed in stimulating the local membrane enzymatic axis, means, and Pitta kapha jwara. For Krimijanya hridroga, Kajjali along effective drug dose decline is followed by inert drug release with Abhraka bhasma levigated in decoction of Terminalia which when declines, again active drug is biochemically arjuna (Arjuna kwath)[41] is beneficial while for Kapha signaled for release.[51] prakopaka, Kajjali, Lauha bhasma, and Pippali churna in honey (Madhu)[42] are prescribed. For various skin troubles including itching (Kandu) and scabies (Pama), Kajjali may CONCLUSION be given with liquid extract of Datura metel leaves (Datura patra swarasa) or with liquid extract of PluImbago Ayurveda encompasses the use of multiple compound zeleynicum (Chitraka Swarasa).[43] For Syphilis (Upadansha), formulations known as Rasa kalpas to provide a near Dwiguna Gandhaka jarita Kajjali is given with clarified immediate relief. However, a detailed study is need of hour butter.[44] For testicular swelling (Muska sosha) Kajjali with to check the pharmacodynamic as well as pharmacokinetics Swarna bhasma and powder of Boerhavia diffusa (Punarnava of these Rasa kalpas and, in particular, the Kajjali, i.e., the churna) may be given.[45] For blood dyscrasias (Rakta pitta), mercury-sulphur compound to understand its role on the Kajjali is advocated either with Emblica officinalis (Amalaki), organs and genetic susceptibility. Piper longum (Pippali), and juice of Adhatoda vasica (Vasa swarasa)[46] or with Swarnamakshika bhasma and honey (Madhu).[46] For respiratory trouble such as breathlessness REFERENCES and cough (Swasa/Kasa), Dwiguna Gandhaka Kajjali is given with Ocimum sanctum (Tulasi), Glycyrrhiza glabra 1. Yogi B, Rastantram R. Rasa chandrika Hindi (Mulethi), Adhatoda vasica (Vasa), Piper longum (Pippali), Commentary. 4th ed. In: Tripathi I, Pant T. Varanasi: Terminalia chebula (Haritaki), and Terminalia bellerica 17/165-166 Chaukhamba Sanskrit Series office; 2001. (Bibhitaka).[47] For night discharge (Swapnameha), Kajjali is 2. Govindpadacharya B. Rasa Hridaya tantra prescribed together with seeds of Elettaria cardamomum Muktavbodhini Sanskrit commentary by Daulat Ram (Ela Beej), Papaver somniferum (Ahiphena), Cinnamomum Shastri. 2nd ed.1/14. Varanasi: Chaukhambha Orientalia; camphora (Kapoor), Myristica fragrans (Jaiphal), and 2001. p. 10. Syzygium aromaticum (lavanga).[48] For Vata roga, Kajjali is 3. Kashinath S. Rasa Tarangini. 6/107. New Delhi: Motilal given with (Triphala churna), purified Commiphora mukul Banarasidas; 1970. p. 124. (Shuddha Guggulu) triturated in oil of Ricinus communis 4. Vagbhat. Rasa Ratna Samuchhaya. In: Kulkarni DA (Eranda taila).[49] For Vamana, Kajjali in combination of editor. 8/5. New New Delhi: Mehar chand Lakshman das Elettaria cardamomum (Ela), Piper nigrum (Maricha), Publication; 1998. p. 145. Syzygium aromaticum (Lavanga), Cinnamomum camphora 5. Nandan MS. Ayurvediya Rasa Shastra. Ch. 2. Varanasi: (Kapoor), Cyperus rotundus (Mustaka), and Ziziphus Chaukhambha Orientalia; 2011. p. 88. mauritiana (Bidara) along with honey (Madhu)[46] is 6. Yogi B, Rastantram R. Rasa chandrika Hindi prescribed. For erysipelas (Visarpa), Dwiguna Gandhaka Commentary.4th ed. In: Tripathi I, editor., 11/199. Kajjali is given with leaf extract of Momordica charantia Varanasi: Taradutta Pant Chaukhamba Sanskrit Series (Karavellaka patra swarasa).[50] For abscess (Vidradhi), office; 2001. p. 116. Kajjali is either given with Varunadi kashaya or given with 7. Sadananda S, Rasa Tarangini. Shastri K, editor. 2/27-8. liquid extract of Moringa oleifera (Sahajana swarasa) mixed New Delhi: Motilal Banarasidas; 1970. p. 16. with honey (Madhu).[51] Henceforth in clinical practice, it is 8. 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In: Mishra GS, editor. Varanasi: Chaukhambha Bharti 37. Sadananda S. Rasa Tarangini. In: Shastri K, editor. Academy; 1999. p. 110. 6/123. New Delhi: Motilal Banarasidas; 1970. p. 127. 19. Vagbhat. Rasa Ratna Samuchhaya. In: Kulkarni SD, 38. Sadananda S. Rasa Tarangini. In: Shastri K, editor. editor. 8/86. New Delhi: Mehar chand Lakshman das 11/68. New Delhi: Motilal Banarasidas; 1970. p. 254. Publication; 1998. p. 145. 39. Sadananda S. Rasa Tarangini. In: Shastri K, editor. 20. Ayurveda Prakash, Madhava AS. Arthavidyotini and 11/72. New Delhi: Motilal Banarasidas; 1970. p. 255. Arthaprakashini Sanskrit and Hindi commentaries. In: 40. Sadananda S. Rasa Tarangini. In: Shastri K, editor. Mishra GS, editor.1/255. Varanasi: Chaukhambha Bharti 12/121. New Delhi: Motilal Banarasidas; 1970. p. 305. Academy; 1999. p. 117. 41. Sadananda S. Rasa Tarangini. In: Shastri K, editor. 21. Ayurveda Prakash, Madhava AS. Arthavidyotini and 10/87. New Delhi: Motilal Banarasidas; 1970. p. 235. Arthaprakashini Sanskrit and Hindi commentaries. 42. Sadananda S. Rasa Tarangini. In: Shastri K, editor. In: Mishra GS, editor. 1/208. Varanasi: Chaukhambha 20/102 New Delhi: Motilal Banarasidas; 1970. p. 512. Bharti Academy; 1999. p. 113. 43. Sadananda S. Rasa Tarangini. In: Shastri K, editor. 22. Ayurveda Prakash, Madhava AS. Arthavidyotini and 6/122. New Delhi: Motilal Banarasidas; 1970. p. 127. Arthaprakashini Sanskrit and Hindi commentaries. 44. Sadananda S. Rasa Tarangini. In: Shastri K, editor. In: Mishra GS, editor. 1/396. Varanasi: Chaukhambha 6/125. New Delhi: Motilal Banarasidas; 1970. p. 127. Bharti Academy; 1999. p. 193. 45. Sadananda S. Rasa Tarangini. In: Shastri K, editor. 23. Sadananda S. Rasa Tarangini. In: Shastri K, editor. 6/121. New Delhi: Motilal Banarasidas; 1970. p. 127. 6/112. New Delhi: Motilal Banarasidas; 1970. p. 126 46. Sadananda S. Rasa Tarangini. In: Shastri K, editor. 24. Ayurveda Prakash, Madhava AS. Arthavidyotini and 6/113. New Delhi: Motilal Banarasidas; 1970. p. 127. Arthaprakashini Sanskrit and Hindi commentaries. 47. Sadananda S. Rasa Tarangini. In: Shastri K, editor. In: Mishra GS, editor. 1/206. Varanasi: Chaukhambha 6/118. New Delhi: Motilal Banarasidas; 1970. p. 127. Bharti Academy; 1999. p. 154 48. Sadananda S. Rasa Tarangini. In: Shastri K, editor. 25. Mishra SN. Dhundhukanāth, Rasendra Chintamani 6/120. New Delhi: Motilal Banarasidas; 1970. p. 127. Siddhiprada Commentary. 1st ed. 3/47-9. Varanasi: 49. Sadananda S. Rasa Tarangini. In: Shastri K, editor. Chaukhambha Orientalia; 2000. p. 25. 6/124. New Delhi: Motilal Banarasidas; 1970. p. 127. 26. Sadananda S. Rasa Tarangini. In: Shastri S, editor. 50. Sadananda S. Rasa Tarangini. In: Shastri K, editor. New Delhi: Motilal Banarasidas; 1970. p. 98. 6/116. New Delhi: Motilal Banarasidas; 1970. p. 127. 27. Savrikar SS, Ravishankar B. Introduction to 51. Sadananda S. Rasa Tarangini. In: Shastri K, editor. “rasashaastra”: the iatrochemistry of ayurveda. Afr J 6/117New Delhi: Motilal Banarasidas; 1970. p. 127. Tradit Complement Altern Med 2011;8:66-82. Available from: http://drshriraj.blogspot.in/2009/01/ 28. Arunachalam J. Researches on mercurial preparations: pharmacology-of-kajjali-kalpas.html. [Last accessed on The prime requirement for their acceptance in medical 2018 March 20]. world. Ayu 2015;36:118-24. 29. Vagbhat. Rasa Ratna Samuchhaya. In: Kulkarni SD, Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S116 Safety of Ayurvedic medicine

Nidhi Nimeshwari, Shuchi Mitra Department of Rasa Shastra and Bhaishajya Kalpana, Rishikul Campus, Uttarakhand Ayurved University, Haridwar, Uttarakhand, India

Abstract

Ayurvedic medicine is one of the world oldest medicine systems. With the increasing use of herbal medicines, its efficacy and safety has become a major concern for health authorities. The WHO estimates that 4 billion people about 80% of world population use Ayurvedic medicine for some kind of primary healthcare. One of the major objectives was to promote safety, efficacy, and quality of Ayurvedic medicine. Research and evaluation of herbal medicines without a long history of use or which have not been previously researched should follow the WHO

REVIEW ARTICLE REVIEW research guidelines for evaluating the safety and efficacy of herbal medicines. In this melee to show efficacy, several positive results related to safety and other purported advantages with Ayurvedic drugs, including improved quality of life, easy drug availability, and less cost, get drowned. To increase the quality of raw herbal drug results in highly safe and effective and quality herbal products, this would accelerate the global acceptance of Indian system of medicine.

Key words: Efficacy, herbal medicine, safety, WHO

INTRODUCTION the prime limb among the Chikitsa Chatushpada (four-fold treatment). Bheshaja includes drugs of herbal, mineral, and Herbal medicine is the oldest form of healthcare animal origin. Each drug (medicine) is procured after proper known to the humanity. For this reason, herbal identification and authentication and is processed in view of medicine has been used therapeutically all its purification thus enhancing the therapeutic properties.[5] around the world and began an important aspect of various traditional medicine system.[1] Although safety is supreme, drug trials in real life are highlighting efficacy more than safety. Hence, this study The WHO research guidelines for evaluating the was envisaged, keeping in view, the safety of Ayurvedic safety and efficacy of herbal medicines can also be medicines as it is equally important in the treatment of consulted for these as well as for other appropriate disorders requiring long-term management.[6] toxicity tests. Only when there is no documentation of long historical use of an herbal medicine, or when doubts exist about its safety, should MATERIALS AND METHODS additional toxicity studies be performed. Where possible, such studies should be carried out in vitro. In general, the traditional procedure-based therapies are Using in vitro tests can be reducing the number of relatively safe, if they are performed properly by well-trained in vivo experiments. If in vivo studies are needed, practitioners. Reported and documented side effects of a herb or they are to be conducted humanely, with respect herb mixture, its closely related species, constituent of the herb for the animals’ welfare and rights. Toxicity studies and its preparation/finished herbal products should be taken should be conducted in accordance with generally into account when decisions are made about the need for new accepted principles, such as those described in pharmacological or toxicological studies. The absence of any WHO research guidelines for evaluating the safety reported or documented side effects is not an absolute assurance and efficacy of herbal medicines.[2] of safety for herbal medicines. Tests which examine effects that are difficult or even impossible to detect clinically should be Currently, an issue is raised with respect to increasing reports of adverse drug reaction Address for correspondence: related to herbal medicines labeled as alternative Nidhi Nimeshwari, Department of Rasa Shastra and medicine and Ayurveda.[3,4] Bhaishajya Kalpana, Rishikul Campus, Uttarakhand Ayurved University, Haridwar, Uttarakhand, India. Today, a need to establish the safety of Ayurvedic Phone: +91-7895299975. medicines has been a challenge posed to the E-mail: [email protected] Ayurvedic fraternity. A Bheshaja (drug) forms

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S117 Nimeshwari and Mitra: SAM encouraged. The WHO research guidelines for evaluating the • Therapeutic procedural complications (Panchakarmavyapad) safety and efficacy of herbal medicines can also be consulted • Improper use of Rasaushadhi (medicines of mineral origin).[9] for these as well as for other appropriate toxicity tests.[7] According to Ayurveda, the formulations contain heavy metals for Herbal medicines are generally regarded as safe based on producing a different effect such as enhancement of bioavailability their long-standing use in various cultures. However, there are of herbs, as a carrier for active principle, and as a catalyst. The case reports of serious adverse events after administration of metals which have been transformed to non-toxic forms are safe herbal products. In a lot of cases, the toxicity has been traced for internal use. After performing the desired action, these metals to contaminants and adulteration. However, some of the plants are eliminated from the body through the excretory system.[10] used in herbal medicines can also be highly toxic. As a whole, herbal medicine can have a risk of adverse effects and drug- drug and drug-food interactions if not properly assessed. CONCLUSION Assessment of the safety of herbal products, therefore, is the priority in herbal research. There are various approaches to the To sum up, herbomineral preparation is safer for both short evaluation of the safety of herbal medicines. The toxic effects term and long term, if each drug (medicine) is procured after of herbal preparation may be attributed mainly to the following: proper identification, authentication, and prepared under • Inherent toxicity of plant constituents and ingredients proper guidance of wise physicians. Further exploration with • Manufacturing malpractice and contamination. larger samples appears necessary to seal the issue. • Requirements for pharmaceutical assessment that cover the safety assessment of herbal products are as follows: • Experience of safety REFERENCES • Toxicological studies, where vindicated.[2] 1. W.H.O. Guidelines for Assessing Quality of Herbal Medicine For herbal products, analysis of the active pharmaceutical with Reference to Contaminants and Residues, W.H.O. ingredients may be best approached by analysis of one or Traditional Medicine Strategy, 2002-2005;. 2007. p. 7, 9.. more hypothesized active ingredients, analysis of a chemical 2. Joshi DR, Joshi G. Quality Control and Standardization constitute that constitutes a sizeable percentage of total of ayurvedic medicines. Varanasi: Chaukhamba ingredients, and chemical fingerprinting of ingredients. Orentalia; 2011. p. 239. 3. Wal P, Wal A, Gupta S, Sharma G, Rai A. Pharmacovigilance Assessment of Safety of herbal products in India. J Young Pharm 2011;3:256e258. 4. Jose J, Rao PG, Kamath MS, Jimmy B. Drug safety reports This should cover all the relevant aspects of the safety on complementary and alternative medicines (ayurvedic assessment of a medicinal product. and homeopathic medicines) by a spontaneous reporting • Specifications of safety parameters. program in a tertiary care hospital. J Altern Complement • Methods and periodicity for assessing and recording Med 2009;15:793-7. 5. Vaghbhatacharya, Aahtang Hridayam Sutra Sthan, 1/27,28, safety parameters. with Sarvangasundhara of Arundutta and Ayurveda • Procedures for eliciting reports of and for recording and Rasayana of Hemadri, collated by Kunte Anna Moreshwar reporting adverse drug reactions and/or adverse events and Navre Krishna Ramachandra Shastri. 8th ed. Varanasi: and intercurrent illnesses. Chaukhamba orientalia, Reprint; 1988. p. 16. • Type and duration of the follow-up of the participants 6. Sarmukadam S, Chopra A, Tillu G. Efficacy and Safety after adverse events. of ayurvedic medicins: Recommending equivalence trial • Information on establishment of the study code, where it design and proposing safety index. Int J Ayurveda Res will be kept and when, how and by whom it can break in [8] 2010;1:175-80. the event of an emergency. 7. World Health Organization. Methodologies for Research and Evaluation of Herbal Medicine. Geneva: WHO; 1988. 8. Drug and Cosmetic Rules, 1945 Edition 25 Eastern DISCUSSION Book Company by Vijay Malik Good Clinical Practice Guidelines for Clinical Trials in India Appendices XLI. Most of the Ayurvedic medicine contained metallic/mineral 2.3.1.8; 1945. p. 1407. components; there were no changes in the safety profile as 9. Ajanal M, Nayak S, Prasad BS, Kadam A. Adverse drug they complied with good manufacturing practice standards. reaction and concepts of drug safety in ayurveda: An However, the toxicity of the metallic preparations as mentioned overview. J Young Pharm 2013;5:116-20. in the other contexts could be due to the following reasons: 10. Berthelot M. The safety of ayurvedic herbo-mineral • Drug interaction (viruddha dravya prayoga) formulations on renal function: An observational study. • Iatrogenic (Vaidhya kruta) Rep Chem Aplique 1859;1:284. • Overdose (At imatra dravya prayoga) • Admiration of unwholesome drugs (Ahitam dravya) Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S118 A review on Yusha Kalpana

Princy Purwar, S. S. Yadav Department of Samhita and Sanskrit, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

In recent decades, there is a sharp increase in lifestyle disorders such as diabetes, obesity, and cardiovascular diseases due to changing dietary habits and increasing sedentary lifestyle. Therefore, we need to be more careful about diet and habits. Since thousands of year, Ayurveda practices Ahara Kalpana for maintaining health and also for prevention and cure many diseases. A set of Ahara Dravya such as Shuka Dhanya and Shimbi Dhanya mentioned in the ancient text. Several pharmaceutical procedures (sanskar) applied on Ahara Dravya to form

REVIEW ARTICLE REVIEW Ahara Kalpana which are manda, peya, vilepi, yusha, yavagu, etc. Yusha being one of them is broadly discussed in every Ayurvedic literature in almost all the diseases. Yusha is prepared by cooking one part of grain other than rice in 16 parts of water. It can be adopted easily as a routine diet for a prolonged time and prevents the progress of diseases in individuals of any age group. This paper is an effort to provide benefits of Yusha Kalpana and explore its therapeutic uses in day to day practice.

Key words: Ahara Kalpana, Ayurvedic pharmaceutics, Yusha

INTRODUCTION condition, making it easily available to the system. Yusha can also enhance palatability and absorption of drugs added to it. ccording to Charaka Samhita, the Thus, Yusha makes treatment more effective. Thus, this article distinction between health and disease emphasizes a different type of Yusha described in different Aarises as the result of the difference texts along with their therapeutic effect. between Pathya (wholesome) and Apathya (unwholesome diet) Ahara.[1] Even hundreds of medicines cannot cure a disease in the absence AIM AND OBJECTIVE of wholesome regimen. Ahara is one of the factors among the three Upastambha (Ahara, The aim of this study is to explore a different type of Yusha Nidra and Brahmacharya) essential for smooth mentioned in various texts, which could be beneficial for a running of life.[2] Ahara Dravya are classified patient suffering from different diseases and also for healthy by Acharya Charaka into 12 subdivisions such individuals. as a set of cereals, legumes, fruits, and milk and milk product. Kritanna Varga is one of them.[3] Kritanna Varga is nothing but a list and properties LITERARY REVIEW of different kalpanas made from different Ahara Varga. Ahara Varga such as Shuka Dhanya, The word Yusha signifies liquefaction and metabolization. Shami Dhanya, Mansa Varga, and Shaka Varga The cooked Yusha liquefies the diet what we take and digest cannot be used without applying Kritanna Varga. it.[5] According to Monier William dictionary, Yusha means Hence, Acharyas have mentioned Kritanna soup, broth or the water in which pulse of various kinds Varga to explain the different kalpana. It is has been boiled.[6] Soopa is also a preparation described in the group consisting of food preparations such many ancient texts which is slightly different from Yusha. as manda, peya, vilepi, saktu, odana, yavagu, According to Acharya Sushruta, Soopa which has been well yusha, veshavara, rasala, raga, and shadava. cooked and prepared from dehusked and slightly fried grains. Yusha preparation is one among them. According It is light and beneficial.[7] to Acharya Kashyapa, so many substances such as legume, pulses, vegetables, and meats are Address for correspondence: cooked with water except rice is called Yusha.[4] Princy Purwar, Room No. 65, Nagarjun Girls Hostel, All types of Yusha are liquid in nature. It is the Banaras Hindu University, Varanasi, Uttar Pradesh, India. preparation with a large portion of water and E-mail: [email protected] with the ingredients specific to the diseases

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METHOD OF PREPARATION OF YUSHA Yusha is widely used for administration of unpalatable drugs for purification therapies and also indicated as a diet before One pala of dravya (such as kulathya and mudga) mixed and after purification therapies: with half karsha of sunthi and Pippali Churna and boiled in one prastha or 16 parts of water.[8] According to Kaiyadev Oleation therapy: Yusha is one among 24 kinds of snehana Nighantu, Yusha is prepared by cooking one part of grain in methods.[19] 18 parts of water.[9] Acharya Gangadhar makes a difference between Yusha and Soopa, on the basis of their method of Emesis therapy: Madanaphala can be used in the form of preparation. According to him, slightly fried pulse which is Yusha for Vamana therapy.[20] Snigdha, amala, lavana, and boiled by adding 14 or 18 times of water till half of the liquid Hridhya Yusha are advised in hyperemesis complication.[21] remains is called Yusha. When it is cooked till ¼ of liquid remains, it is called Soopa.[10] Purgation therapy: Sudha can be used in the form of Yusha for purgation therapy.[22] Masha and Kulattha Yusha is indicated in over purgation.[23] As a diet while taking purgative CLASSIFICATION OF YUSHA[11] medicines such as Trivrutadi Virechana Yoga Churna and Danti Dravanti Mula Kwatha.[24] All types of Yusha can be classified into two, namely, Kashaya with Madhura and Kashaya with Amla. On the basis of Medicated enema: Yusha with amala and Lavana Dravya addition of Sneha Dravya, Yusha can be classified into three is indicated in the conditions of Udararoga during their types, namely, Krita yusha for Vata roga, Akritayusha for treatment through Vasti therapy.[25] Kaphajroga, and Akrita - Kritayusha for Pitta roga. On the basis of Veerya of drugs added in it, Yusha is of three types, For Sansarjan karma: After the body is cleansed by namely, drug with sheetaveerya causes brihana, drugs with panchkarma therapies, the patient should be provided ushnaveerya causes karshana, and drugs with mishra veerya with the food such as manda, peya, vilepi, akrita - krita causes pachana. As per classification of doshas, Yusha is 75 yusha, and akrita - krita mansa rasa.[26] Yusha of husk free in number. Depending on rasa, Yusha is 50 in number. On mudga, virasika (Yusha of mudga and takramla), Dadima the basis of ingredients, Yusha is 25 in number which are Yusha, and Dhatri Yusha can be used after purification.[27] described in detail in Kashyapa Samhita. Yusha mixed with dadhi, kanjika, sukta, and Deepan Dravya is contraindicated for this purpose.[28]

PROPERTIES OF YUSHA[12] Miner surgical procedures - Yusha is suggested during Agnikarma in Pleehodararoga.[29] Yusha cooked with various drugs capable of suppressing different diseases. Yusha can be taste enhancer, appetizer, aphrodisiac, improve voice, complexion, strength, and agni, DISCUSSION diaphoretic; it brings satisfaction, nourishment, and pleasure. It can bring proper nourishment both mentally and physically There is a large number of Yusha found in every classic and in giving a sense of comfort. Yusha can suppress all three dosha almost all the disorders. Most of the Acharya described Yusha on the basis of drug added in it. It suppresses Vata Dosha due under Kritanna Varga, but Acharya Kashyapa describes it to snigdha and usna properties, suppresses pittadosha due to as separate chapter. Yusha Kalpana has been described in sneha and kashaya nature, and sesuppresses kaphadosha due Kashyapa Samhita with a specific aim. Yusha is more liquid to ushna and katu properties. in nature. Due to liquid consistency, Yusha can be used widely in pediatric age group patient. Yusha described in Table 1 below with their ingredients and therapeutic properties and uses. Yusha and Soopa are two preparations given by Acharya Charaka which looks similar, but there is the difference between them. Acharya Charaka has not mentioned their method of OTHER USES OF YUSHA preparations. The method of preparation of Yusha is described in Sharngadhara Samhita and Kaiyadev Nighantu. Acharya Acharya Charaka mentioned in ritucharya that Yusha mixed Gangadhar makes a difference between Yusha and Soopa, on with jangalmansarasa should be taken in rainy season.[13] the basis of the method of preparation. The property of Yusha is Yusha is said to be taken as Anupan in tailapana[14] and while greater than that of Soopa because it is formed by the combination takin Gamalaka Rasayana[15] and Haritakyadi Yoga.[16] of various substances. In the present scenario, Yusha is compared Bhallataka Rsayana can be taken in the form of Yusha to with soup formed by the combination of different vegetables, etc. reduce its toxic effects on the body.[17] For the alleviation of jwara, if kapha is dominant, then Yusha should be used as a Ayurveda gives more importance to digestion of food in meal for 10 days.[18 ] comparison to nutrition. It is believed that only properly

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Table 1: Ingredients, therapeutic properties and uses of different Yusha Name of Yusha Ingredients Therapeutic property and uses Reference Chitraka Yusha Chitraka Pacify kapha and Vata Dosha. Kashyapa Samhita Khi. Enhance agni in disease such as 4/38‑40 Grahani Dosha, Pleeha Roga, arsha, gulma, kushtha, and hridrog Panchkolaka Yusha Sati, karkataki, bilva, Grahi Cures atisara, grahani, Kashyapa Samhita Khi. ajashringi, Pushkar Dhataki, pravahika in niarama condition. 4/40‑42 dadhittha, dadima, changeri, and samanga Dadhimanda and Takra Any Shimbi Pathya in Shira, chakshu, karna Kashyapa Samhita Khi. Siddha Yusha Dhanya+Dadhimanda and and hridroga, and ardhavabhedaka. 4/44‑45 takra Cures aruchi and atisara if taken with tila and masha. Phala Yusha Unripe fruits of kapittha, Cures chronic atisara Kashyapa Samhita Khi. bilva, badara, dadima, and 4/46‑47 aamra Pushpa Yusha Decoction of flower of sana, If cooked with dadima without Kashyapa Samhita Khi. shalmali, dhataki, padma, sneha and amala dravya, cures 4/47‑49 saugandhika, kovidara, and Asrigdara, Raktapitta, and daah karbudara Patra Yusha Decoction of leaves of bilva, Eradicates Vata Dosha Kashyapa Samhita Khi. sobhanjana, eranda, bala, 4/49‑50 raasna, and aamra Valka Yusha Decoction of bark of Cures atisara Kashyapa Samhita Khi. dadima, aamra, jambu, and 4/50‑51 chirabilva with dadhimanda Pallava Yusha Decoction of tender leaves If cooked with ghrita and dadima, Kashyapa Samhita Khi. of nyagrodha, udumbara, Cures garbhapata, and daah 4/51‑53 plaksha, palasa, and kamal Vatahara Yusha Yusha of punarnava, Eradicate vata dosha Kashyapa Samhita Khi. raasna, changeri, and bala 4/53‑54 prepared separately with dadhi and ghrita Kambalika Rohita fish cooked Brighana, balya in nature and pacify Kashyapa Samhita Khi. decoction cooked with 1 vata dosha. If cooked with tila tail, 4/54‑57 kudava of sukta, kanji, enhance rati (sexual pleasure), Dadhi Mastu, and 5 Pala nidra, and ruchi (appetite). Guda (jaggery). Maha Yusha Decoction of Deepaneeya Pacify all three dosha. Cures Kashyapa Samhita Khi. Panchmoola, fruits atyagni, anidra, stabdhta, atisara 4/57‑63 of Madhura Gana Dravya, all dhanya, dhanyaka, maricha, and kakolietc.+dadhi, kanji+tail, ghrita+Moolaka+trikatu Lasuna Yusha Lasuna Cures Bhagna, all Vataj Roga, kaas, Kashyapa Samhita kushtha, kilasa, krimiroga, gulama, Kalp. 2/26‑27 and Jeerna Jwara Moolaka Yusha Kulattha and moolaka Can cure all the diseases. Specially Kashyapa Samhita Khi. Ajeerna and rajyakshma. 4/65‑66 and Ch. Chi. 8/68 Mansa Yusha Meat of laavaka (quail) Mixed with ghrita, without Amla Kashyapa Samhita Khi. Dravya pacify pitta dosha and with 4/66‑67 Sneha Dravya pacify Vata Dosha

(contd...)

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Table 1: (Continued) Name of Yusha Ingredients Therapeutic property and uses Reference Mudga Yusha Mudga, saidhava lavana, Pacify kapha and Pitta Dosha. Kaiyadeva Nighantu sunthi, dhanyaka, pippali, Pathya in hridroga, raktapitta, 5/65‑66 and jeeraka trishna, daah, jwara, vrina, Urdha Jatrugata Roga, and increases agni Masooradi Yusha Masoora, mudga, godhuma, Pacify Vata Dosha. Does not Kaiyadeva Nighantu kulattha, and lavana increases pitta and Kapha Dosha 5/69

Mridwikadi Yusha Mridwika, Dadima, and 5 Pathya for aruchi, hridroga, and Kaiyadeva Nighantu lavana vataroga 5/70 Shooka Dhanya Yusha Shooka Dhanya, patola, and Pacify kapha and Pitta Dosha. Kaiyadeva Nighantu nimba Pathya in hridroga and medoroga. 5/71‑72 Cures krimi, kushtha, and jwara. Supya Yusha Any Shimbi Dhanya and Pacify Kapha Dosha. Cures kaas, Kaiyadeva Nighantu moolaka pratisyaya, praseka, aruchi, jwara, 5/72‑73 and Kantha Roga Kulatthya pancha Yusha Kulttha, maasha, nishpav, Pacify Kapha Dosha. Cures all Kaiyadeva Nighantu mudga, and adhaki type of jwara, shoola, and kshaya. 5/73‑74 Cause snehana. Aranya Mudga Yusha Vana Mudga Pacify pitta dosha. Brihana Kaiyadeva Nighantu and vrishya in nature. Cures 5/75‑76 mutrakrichha, jwara, and raktapitta. Kulattha Yusha Kulattha Pacify tridosha and causes Kashyapa Samhita rukshana. Cures gulma, arsha, Khi. 4/4546 Kaiyadeva prameha, medaroga, ashmari, Nighantu 5/76‑77 sharkara, kaasa, shwasa, and tuni‑pratuni. Adhaki Yusha Adhaki Pacify all three dosha. Cures jwara, Kaiyadeva Nighantu kaasa, shwasa, raktagata vyadhi, 5/78 peenasa, and krimiroga. Chanaka Yusha Chanaka Pacify all three dosha. Cures kaas, Kaiyadeva Nighantu shwasa, pratisyaya, and raktapitta. 5/79 Masoora Yusha Masoora Grahi and brihana in nature and Kaiyadeva Nighantu cures prameha 5/80 Maasha Yusha Maasha Vitiate all three dosha. Increases Kaiyadeva Nighantu Sukra Dhatu and increases mala in 5/80‑81 koshtha Nishpaav Yusha Nishpaav Pacify Kapha Dosha. stanyajanana Kaiyadeva Nighantu 5/81 Panchmushthika Yusha Yava, kola, kulattha, mudga, Pacify all three dosha. Cures Kaiyadeva Nighantu and moolaka shoola, kaasa, shwasa, gulma, 5/82‑83 kshaya, and jwara Navanga Yusha Mudga, kola, pippali, Pacify pitta and Kapha Dosha Kaiyadeva Nighantu shunthi, amalaki, moolaka, 5/84 kulattha, and tandula Dadima Amalaka Yusha Dadima and amalaka Pacify vata and Pitta Dosha. Pathya Kaiyadeva Nighantu for hridrog and Visha Rogi. Cures 5/85 and Ch. Chi. mada and murchha 23/226 Mudga Amlaka Yusha Mudga and amalaka Pacify pitta and Kapha Dosha and Kaiyadeva Nighantu cures constipation and pathya for 5/86 and Ch. Chi. Visha Rogi 23/226 Khada Yusha Kapittha, vilva, changeri, Pacify vata and Pitta Dosha. Pathya Kaiyadeva Nighantu maricha, jeeraka, and for hridrog and vamana. 5/86‑88 Chitraka Siddha Yusha (contd...)

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Table 1: (Continued) Name of Yusha Ingredients Therapeutic property and uses Reference Kambalika Yusha Dadhi, amla, sneha, lavana, Pacify vata and Pitta Dosha. Pathya Kaiyadeva Nighantu tila, and maasha for hridrog and vamana. 5/87‑88 Rasna Yusha Rasna, bala, laghu Cures hikka and Shwasa Roga Charaka Chikitsa 17/96 panchmool, and chitraka Matulunga Yusha Matulunga, nimbi, patola, Cures hikka and Shwasa Roga Charaka Chikitsa 17/97 mudga, and trikatu Kasamarda/ Kasamarda/shobhanjana/ Cures hikka and Shwasa Roga Charaka Chikitsa 17/99 Shobhanjana/Moolaka moolaka Yusha Mudga Kantakari Yusha Mudga and kantakari Cures All Types Of Kaasa Roga Charaka Chikitsa 18/184 Maash‑atamgupta Yusha Masha and atmagpta Yusha Cures Vataj Kaasa Charaka Chikitsa 18/76 Grinjanaka Yusha Grinjanaka (carrot) and Cures atisaara Charaka Chikitsa 19/38 Amla Dravya Patola Yusha Patola and amalaka Cures visharpa and Kaphaj Charaka Chikitsa Madaatya 21/111 and 24/171 Shigru Yusha Shigru and Dadhi Mastu Cures ashmari Charaka Chikitsa 26/66 Vartakadi Yusha Vartaka, kulaka, trikatu, Cure Kaphaj Pratisyaya Charaka Chikitsa kulattha, aadhaki, and 26/156 mudga digested food can provide proper nutrition to the body. Yusha There are a number of Yusha described in Ayurvedic texts. being liquid in nature, can be easily digested and also enhance Dravya which is used in the time of Samhitas is different, and agni for digestion of other substance as well. It can also their preparation methods are also changed. Many classical enhance the palatability of medicine and make katu, Tikta dravya is not in practice today. Therefore, it is intellect of Dravya more acceptable for the patient. This preparation is physician to choose the type of Yusha, their ingredients, and a better option for patient of pediatric age group or mental methods of preparation for the benefit of healthy individuals patient to administered drugs. It also excludes harmful and as well as patients suffering from different diseases. poisonous effect of drug. It also checks irritation and burning that occurs after administration of ushna and teeksha drugs. CONCLUSION Achaya Charaka classify Yusha into two types, i.e., Krita Yusha and Akrita Yusha, on the basis of addition of Lavana Description of Yusha Kalpana is found in Brihat-trayi, but Katu and sneha substances in it. Akrita Yusha should be there is a lack in their method of preparations, which is later used in those patients who have very poor digestive power described by other Acharya. Detailed description of Yusha or weak due to chronic disease. Acharya Kashyapa gives Kalpana is found in Kashyapa Samhita and Kaidev Nighantu. a very detailed description of Yusha. He made several Yusha being easy to prepare can be adopted easily by patients classifications of Yusha. First one is of two types, i.e., of many acute and chronic diseases. Yusha is indicated as diet Kashaya-madhura and Kashaya-amala. Kashaya-madhura therapy during and after purification therapy, for a person Yusha can be prescribed in weak patient or inpatient of under medication, as an Anupaan with many food articles Rakta Pitta, Rakta Atisara, raktarsha, visharpa, etc., and and medicine. Yusha being liquid in nature and tasty in taste, Kashaya-amala Yusha prescribed in patient of aruchi, it can be very good diet for children. Moreover, it can also be chhardi, atisara, etc. These classification mentioned in used to enhance the palatability of many drugs. The food we Kashyapa Samhita, helps us in deciding type of Yusha for take should be incorporated with Yusha Kalpana. It would be particular disease or individual. more congenial and is advised for both healthy and diseased and is also said as health promotive. Khada and kambalika are types of Yusha described by many Acharyas. Acharya Chakrapani and Dalhana considered khada as a preparation of Yusha mixed with vegetables and REFERENCES pulses, but Acharya Vagabhata considered Khada as Yusha prepared from fruits. Kambalika is the type of Yusha which is 1. Samhita AC, Commentary VH, Kashinatha S, soured with curd water. Sutrasthan CG. Vividhashitapitiya Adhyaya (28; 45).

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Varanasi: Chaukhambha Bharati Academy; 2013. p. 575. Chaukhambha Bharati Academy; 2013. p. 19. 2. Samhita AC, Commentary VH, Kashinatha S, 17. Samhita AC, Commentary VH, Kashinatha S, Sutrasthan CG. Tisraishneeya Adhyaya (11; 35). Gorakhnatha C. Chikitsasthan, Rasayana Adhyaya (1, Varanasi: Chaukhambha Bharati Academy; 2013. p. 227. 3; 16). Varanasi: Chaukhambha Bharati Academy; 2013. 3. Samhita AC, Commentary VH, Kashinatha S, p. 33. Sutrasthan CG. Annapaanvidhi Adhyaya (27; 6, 7). 18. Samhita AC, Commentary VH, Kashinatha S, Varanasi: Chaukhambha Bharati Academy; 2013. p. 526. Gorakhnatha C. Chikitsasthan, Jwarachikitsa Adhyaya 4. Samhita KK. English Translation and Commentary, (3; 163). Varanasi: Chaukhambha Bharati Academy; Tiwari PV, Khilasthana, Yushanirdesheeya Adhyaya 2013. p. 141. (4; 18, 19). Varanasi: Chaukhambha Bharati Academy; 19. Samhita AC, Commentary VH, Kashinatha S, 1996. p. 470. Gorakhnatha C. Sutrasthan, Snehaadhyaya (13/23). 5. Samhita KK. English Translation and Commentary, Varanasi: Chaukhambha Bharati Academy; 2013. p. 262. Tiwari PV, Khilasthana, Yushanirdesheeya Adhyaya 20. Samhita AC, Commentary VH, Kashinatha S, (4; 17,18). Varanasi: Chaukhambha Bharati Academy; Gorakhnatha C. Kalpasthan, Madanphalakalpa Adhyaya 1996. p. 470. (1/26). Varanasi: Chaukhambha Bharati Academy; 2013. 6. E-Samhita Designed and Developed by National p. 901. Institute of Indian Medical Heritage. Monier-Williams 21. Samhita AC, Commentary VH, Kashinatha S, Gorakhnatha C. Dictionary, L-38834, p-0821-b, Ayush_Sanskrit _eBook. Siddhisthan, Vamanavirechanavyapadasiddhi (6/54). Varanasi: Hyderabad: e-Samhita Designed and Developed by Chaukhambha Bharati Academy; 2013. p. 1027. National Institute of Indian Medical Heritage; 2008. 22. Samhita AC, Commentary VH, Kashinatha S, 7. Samhita SS, Commentary AT, Sutrasthana AT. Gorakhnatha C. Kalpasthan, Sudhakalpa Adhyaya Annapaanvidhi Adhyaya (46; 352). Varanasi: (10/19). Varanasi: Chaukhambha Bharati Academy; Chaukhambha Sanskrita Sansthana; 2014. p. 272. 2013. p. 934. 8. Srikanta MK. Sharngadhara, Sharngadhara Samhita. 23. Samhita AC, Commentary VH, Kashinatha S, Madhyama Khanda, Kwatha Kalpana (2; 154). Varanasi: Gorakhnatha C. Siddhisthan, Prasritayogeeyasiddhi Chaukhambha Orientalia; 2001. p. 74. (8/18). Varanasi: Chaukhambha Bharati Academy; 2013. 9. Sharma PV, Prasad SG. Kaiyadeva, Kaiyadeva Nighantu, p. 1045. Kritanna Varga (5; 62). Varanasi: Chaukhambha 24. Samhita AC, Commentary VH, Kashinatha S, Orientalia; 2009. p. 411. Gorakhnatha C. Kalpasthan, Shyamatrivritakalpa 10. Samhita AC, Commentary J, Nath GS, Adhyaya (7/65). Varanasi: Chaukhambha Bharati Vividhashitapitiya SS. Adhyaya, Commentary on (27; Academy; 2013. p. 925. 349). Varanasi: Chaukhambha Bharati Academy; 1984. 25. Samhita AC, Commentary VH, Kashinatha S, p. 1080. Gorakhnatha C. Chikitsasthan, Udararogachikitsa 11. Samhita KK. English Translation and Commentary, Adhyaya (13/63). Varanasi: Chaukhambha Bharati Tiwari PV, Khilasthana, Yushanirdesheeya Adhyaya Academy; 2013. p. 393. (4; 24-29). Varanasi: Chaukhambha Bharati Academy; 26. Samhita AC, Commentary VH, Kashinatha S, 1996. p. 471. Gorakhnatha C. Siddhisthan, Kalpanasiddhi Adhyaya 12. Samhita KK. English Translation and Commentary, (1/11). Varanasi: Chaukhambha Bharati Academy; 2013. Tiwari PV, Khilasthana, Yushanirdesheeya Adhyaya p. 961. (4; 14-17). Varanasi: Chaukhambha Bharati Academy; 27. Samhita KK. English Translation and Commentary, 1996. p. 470. Tiwari PV, Khilasthana, Yushanirdesheeya Adhyaya 13. Samhita AC, Commentary VH, Kashinatha S, (4; 35-37). Varanasi: Chaukhambha Bharati Academy; Gorakhnatha C. Sutrasthan, Tasyaashiteeya Adhyaya (6; 1996. p. 473. 38). Varanasi: Chaukhambha Bharati Academy; 2013. 28. Samhita KK. English Translation and Commentary, p. 143. Tiwari PV, Khilasthana, Yushanirdesheeya Adhyaya 14. Samhita AC, Commentary VH, Kashinatha S, (4; 32, 33). Varanasi: Chaukhambha Bharati Academy; Gorakhnatha C. Sutrasthan, Snehaadhyaya (13/22). 1996. p. 473. Varanasi: Chaukhambha Bharati Academy; 2013. p. 261. 29. Samhita AC, Commentary VH, Kashinatha S, 15. Samhita AC, Commentary VH, Kashinatha S, Gorakhnatha C. Chikitsasthan, Udararogachikitsa Gorakhnatha C. Chikitsasthan, Rasayana Adhyaya (1,1; Adhyaya (13/88). Varanasi: Chaukhambha Bharati 75). Varanasi: Chaukhambha Bharati Academy; 2013. Academy; 2013. p. 397. p. 17. 16. Samhita AC, Commentary VH, Kashinatha S, Gorakhnatha C. Chikitsasthan, Rasayana Adhyaya (1,1; 77). Varanasi: Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S124 A phytochemical study of medicinal plant extract

P. S. Upadhyay Department of Kaumarbhritya, FOAy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

Aim of Study: The aim of this study was the phytochemical evaluation of extract of the Musta, Pippali, Ativisha, and Karkatshringi. All these drugs have been described to have antidiarrheal properties and antimicrobial properties in different texts. Materials and Methods: The dried samples were resuspended in high-performance liquid chromatography (HPLC)-grade methanol for HPLC analysis. Shimadzu LC-10A (Japan) was used that was equipped with dual pump LC-10A binary system. Shimadzu Class VP series software was used to integrate ORIGINAL ARTICLE ORIGINAL the data separation of phenolics was achieved with acetonitrile/water (1:1 v/v) containing 1% acetic acid in a linear gradient program. The solvent flow rate was 1.0 ml min−1. Results: In phytochemical study, six phenolic acids were detected in the four plant samples. Of the six phenolic standards used, Ativisha contained only one phenolic compound, whereas Musta and Pippali contained five compounds. Only two phenolic compounds were detected in Karkatshringi. Of the seven phenolic standards used, Draksha contained four compounds, whereas Vasa and Haritaki contains five compounds while Pippali contains six phenolic compounds. Conclusion: It means Balchaturbhadra yoga having high antioxidant property.

Key words: Balchaturbhadra yoga, high-performance liquid chromatography, medicinal plant, phytochemical

INTRODUCTION year.[5] Overall, the prevalence being significantly higher in children <2 years as compared to those 2–5 years.[6] Mostly, acterial pathogens were identified in acute diarrhea is infectious in origin in childhood. Bacterial majority of patients in developing pathogens were identified in the majority of patients in countries. Etiological spectrum varies developing countries. Etiological spectrum varies during B different seasons and different geographic settings. Diarrheal during different seasons and different geographic settings. In the developed countries, it is estimated disease remains an important cause of death and morbidity in that over 50% of acute diarrhea are caused by developing countries with an estimated 1.5 million episodes viruses including Rotavirus, Norwalk virus, and 1.5 million–2.5 million deaths each year among children and coronavirus. Human Rotavirus is the most younger than 5 years.[7] It still continues to be a major cause important etiological agents of acquired diarrhea of hospitalization and death in <5-year-old children and has in infants and young children worldwide.[1] The severe economic consequences.[8] bacterial agent that is known to cause diarrhea is Escherichia coli (20% of all cases of acute diarrhea The present study was conducted to investigate phytochemical are due to E. coli, V. cholerae (cholera accounts study of extract of the Musta, Pippali, Ativisha, and for 5–10% cases), Clostridium difficile, Shigella, Karkatshringi. All these drugs have been described to Salmonella (3–7% of childhood diarrhea), have antidiarrheal properties and antimicrobial properties Campylobacter, and Yersinia enterocolitica.[2] in different texts. The present in vitro study was initiated to evaluate the efficacy of these drugs, which may help in Diarrhea is the third most common cause ascertaining the mode of action as well as further specific use of death in under-five children, responsible of the present combination in future in vivo studies. for 13% of deaths in this age group, killing an estimated 300,000 children in India each Address for correspondence: year.[3] Infectious diarrhea is considered the Dr. P. S. Upadhyay, Department of Kaumarbhritya, FOAy, second most common cause of morbidity and Institute of Medical Sciences, Banaras Hindu University, mortality worldwide.[4] Global annual burden Varanasi, Uttar Pradesh, India. of diarrhea is huge affecting 3–5 billion cases Phone: +91-9415624827. E-mail: [email protected] and causing approximately 2 million deaths a

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S125 Upadhyay: Phytochemical study of medicinal plant

Table 1: Phenolic acid contents in medicinal plant Sr. no. Phenolic compounds Musta (µg/ml) Pippali (µg/ml) Ativisha (µg/ml) Karkatshringi (µg/ml) 1. Shikimic acid 140 1068 498.5 - 2. Gallic acid 31.9 265 - - 3. Syringic acid - 4.5 - 38.6 4. Quercetin 8.3 - - - 5. Cinnamic acid 10.9 1.4 - 22.5 6. IAA 46.5 92.8 - -

MATERIALS AND METHODS contained only one phenolic compound, i.e. shikimic acid, whereas Musta and Pippali contained five compounds as Plant Materials shown in the table. Syringic acid was not detected in Musta and quercetin was not detected in Pippali. Only two phenolic For this study, fruits of Piper longum L., rhizome of Cyperus compounds, i.e., syringic and cinnamic acids were detected rotundus L., root of Aconitum heterophyllum, and galls in Karkatshringi. of Pistacia integerrima were collected from Haridwar, Uttarakhand. The plant was identified and authenticated by the Professor N. K. Dubey, Department of Botany, Banaras DISCUSSION AND CONCLUSION Hindu University, Varanasi, with the voucher specimen no: 1. P. integerrima Stewart ex Brandis - Anacard. 2014/1. In phytochemical study, of the six phenolic standards 2. C. rotundus L. - Cyper 2014/1. used, Ativisha contained only one phenolic compound, 3. P. longum L. - Piper 2014/1. i.e., shikimic acid, whereas Musta and Pippali contained 4. A. heterophyllum Wall. Cat. - Ranun 2014/1. five compounds as shown in Table 1. Syringic acid was not detected in Musta and quercetin was not detected in Pippali. Only two phenolic compounds, i.e., syringic and cinnamic Preparation of Extracts acids were detected in Karkatshringi. The beneficial effects derived from phenolics compounds have been attributed to For the study, dry extract of each drug was prepared in the their antioxidant activity.[9] It means Balchaturbhadra yoga laboratory of the Department of Medicinal Chemistry, IMS, has high antioxidant property. BHU. Aqueous extract of drugs was prepared by water decoction method and alcoholic extract was prepared by Soxhlet method of extraction. Both the extracts were collected REFERENCES in separate sterile vials and preserved at 4°C temperature. 1. Chang HG, Glass RI, Smith PF, Cicirello HG, The phytochemical study was carried out in the Department Holman RC, Morse DL, et al. Disease burden and risk of Mycology and Plant Pathology, Institute of Agricultural factors for hospitalizations associated with rotavirus Sciences, BHU, Varanasi. The dried samples were resuspended infection among children in New York State, 1989 in high-performance liquid chromatography (HPLC)-grade through 2000. Pediatr Infect Dis J 2003;22:808-14. methanol for HPLC analysis. Shimadzu LC-10A (Japan) was 2. CBS publishers. GHAI Essential Pediatrics. 18th ed. used that was equipped with dual pump LC-10A binary system, New Delhi: CBS Publishers; 2013. UV detector SPD-10A, and Phenomenex (Torrance, USA) 3. Million Death Study Collaborators, Bassani DG, C18 column (RP-Hydro, 4 μm, 250 mm × 4.6 mm). Shimadzu Kumar R, Awasthi S, Morris SK, Paul VK, et al. Class VP series software was used to integrate the data. Causes of neonatal and child mortality in India: Separation of phenolics was achieved with acetonitrile/water A nationally representative mortality survey. Lancet (1:1 v/v) containing 1% acetic acid in a linear gradient program 2010;376:1853-60. −1 (Singh et al., 2009). The solvent flow rate was 1.0 ml min . 4. Wolfe MI, Nolte KB, Yoon SS. Fatal infectious disease surveillance in a medical examiner database. Emerg Infect Dis 2004;10:48-53. OBSERVATIONS AND RESULTS 5. Paul V, Bagga A. GHAI Essential of Pediatrics, Acute Diarrhea. New Delhi: CBS Publishers and Distributers Concentration of the phenolic compounds in the four plants Pvt. Ltd.; 2013. p. 291. is as follows: 6. Ameta T, Nayak VH, Goyal SC. Prevalence and Seasonal distribution of Rotavirus diarrhea in hospitalized children Table 1 shows that six phenolic acids were detected in the four less than 5-year-old in South Rajasthan. Int J Biomed plant samples. Of the six phenolic standards used, Ativisha Res 2015;6:214-8.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S126 Upadhyay: Phytochemical study of medicinal plant

7. Duggan C, Fontaine O, Pierce NF, Glass RI, 9. Wright RJ, Cohen S, Carey V, Weiss ST, Gold DR. Mahalanabis D, Alam NH, et al. Scientific rationale for Parental stress as a predictor of wheezing in infancy: a change in the composition of oral rehydration solution. A prospective birth-cohort study. Am J Respir Crit Care JAMA 2004;291:2628-31. Med 2002;165:358-65. 8. Bhan MK. Current Concepts in Management of Acute Diarrhea, Department of Pediatrics. New Delhi, India: All India Institute of Medical Sciences; 2005. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S127 Biological activity and medicinal uses of neem

Renu Srivastav, Vandna Pathak Department of Physical Sciences, Mahatma Gandhi Chitrakoot Gramoday Vishwavidyalaya (Behind of Mission Hospital Karwi), Satna, Madhya Pradesh, India

Abstract

Neem has become valuable tree in the world which shows the solution for many problems. Neem is an evergreen tree which is native of India, Africa, and Bangladesh. Neem shows various biological activities such as antibacterial, antimalarial, antiulcer, and anticancerous activities. This review article focuses on antifungal and antibacterial

REVIEW ARTICLE REVIEW activity.

Key words: Antibacterial, biological activities, evergreen tree, neem

INTRODUCTION 4. Remove toxins, purify blood, and prevent damage caused by free radical in the body neutralizing them. n human society from immemorial medicinal plant has played an important ANTIBACTERIAL ACTIVITY Irole in prevention and control of diseases (Chibber S and Sharma N). Neem is very The in vitro effect of crude extract of leaves of A. indica in common tree in India. It is large evergreen ethanol hexane and ethyl acetate gave varied result for various dense tree some 10–15 m tall (Shrivastava microbes such as Escherichia coli, Pseudomonas, Bacillus et al.). Azadirachta indica is rapidly growing subtilis, and Staphylococcus aureus. Ethanol extract found evergreen plant found in America, Africa, and most effective for all microbes, whereas ethyl acetate extract India (Pingale Sirish et al.).[1] A. indica has been showed minimum antimicrobial activity.[2] Neem extract used for their healing powers since ancient time of methanol, hexane, and chloroform was compared with (Pratibha Prasharar). Neem tree has attracted penicillin. Hexane extract of neem found effective against worldwide prominence showing to its wide Proteus vulgaris and Micrococcus leuteus, and Streptococcus range of medicinal properties. showed maximum inhibition zone 18.33 mm. The maximum inhibition zone showed by chloroform against Proteus vulgaris is 31 mm and maximum inhibition zone showed by methanol Taxonomy extract is 33 mm.[3] Leaf and bark aqueous and alcohol extract of A. indica were tested against E. coli and Staphylococcus, Kingdome - Plantae and it was reported that ethanol extract effective than aqueous Division - Magnoliophyta extract against microbes.[4] Leaf, bark, and seed aqueous extract Class - Magnoliopsida were tested against various bacteria and reported that the Order - Sapindales aqueous extract of neem leaf exhibited highly antibacterial.[5] Family - Meliaceae Genus - Azadirachta Species - A. indica. ANTIFUNGAL ACTIVITY

Methanol extract of neem showed recorded mycelium MEDICINAL USES growth again three species of fungi are Aspergillus viridae, 1. Cough, fever, loss of appetite, and worm Address for correspondence: infections. Renu Srivastav, Department of Physical Sciences 2. Used in vomiting, skin diseases, and Mahatma Gandhi Chitrakoot Gramoday Vishwavidyalaya, reduces high blood pressure. Behind of Mission Hospital Karwi, Satna, Madhya 3. Used to treat arthritis, malaria, diabetes Pradesh, India. E-mail: [email protected] liver disease, and cancer.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S128 Srivastav and Pathak: Neem, a beneficial tree for human

Penicillium digitatum, and Rhizopus which separated by extracts and the nimonol against some important tomatoes. The maximum inhibition zone showed in all fungi human pathogens. Braz J Microbiol 2011;42: at 20% concentration and minimum inhibition zone in 60% 1007-16. of concentration. The study shows that the effectiveness 2. Pruthi PH, Akhlaq A. In vitro antibacterial activity of of extract on the fungi is decreases with increasing the Azadirachta indica indica against pathogenic bacteria. J concentration.[6] The extract of methanol and water was Pharm Res 2012;5:363-4. compared against Aspergillus and Rhizopus and found that 3. Budida KS. Antibacterial potential of the extract of methanol extract shows maximum effectiveness against the leaves of Azadirachta indica linn. Natl Sch Bus fungi as compared to water extract.[7] Leaf bark and seed 2011;3:65-9. extract were tested against various fungi and reported that the 4. Francine U, Jeannette U, Pierre RJ. Assessment aqueous extract of neem leaf exhibited highly antifungal.[5] of antibacterial activity of neem plant on Staphylococcus aureus and E. coli. J Med Plants Stud 2015;3:85-91. CONCLUSION 5. Reddy Y, Kumari CK, Loknatha O, Mamatha S, Reddy CD. Antimicrobial activity of Azadirachta indica A. indica (neem) is a medicinal tree that has been found leaf, bark and seed extracts. Int J Res Pharm Pharm effective in the treatment of bacterial and fungal disease 2015;3:1-4. and revealed antibacterial and antifungal activities. Due to 6. Suleimen MN. Antifungal properties of leaf extract of increasing of antibiotics resistant to bacteria and fungus and neem and tobacco on three fungal pathogens of tomato. side effect, neem trees are the best option for medicine. The Adv Appl 2011;2:217-20. present study determines that neem has real potential for the 7. Mondali NK, Chatterje MA, Banerjee A, Datta JK, treatment of fungal and bacterial infection. Gupta S. Antifungal activities and chemical chacterization of neem leaf extract on the growth of some selected fungal in vitro culture medium. J Appl Sci REFERENCES Environ Manage 2009;13:49-53.

1. Mahmoud DA, Hassanein NM, Youssef KA, Abou Zeid MA. Antifungal activity of different neem leaf Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S129 State of the art toward the management of prameha (diabetes) ascribed by Dhanvantari Nighantu

Roli Sarjuprasad Mishra1, Anil Kumar Singh1, Sudheer Kumar Kushwaha2, Sapna Chaudhary1 1Department of Dravyaguna, Faculty of Ayurveda, I.M.S., B.H.U., Varanasi, Uttar Pradesh, India, 2Department of Shalakya Tantra, Faculty of Ayurveda, I.M.S., B.H.U., Varanasi, Uttar Pradesh, India

Abstract

REVIEW ARTICLE REVIEW At the present time a major population of the world, as well as our country, is suffering from a serious metabolic syndrome - diabetes. Allopathic drugs are having a limitation on the management of diabetes (Prameha) because there are so many adverse effects, so we cannot use these medicines for a long time. We found that there is a need of some search for herbal remedies in ayurvedic scripture like Dhanvantari Nighantu for the treatment of this life-threatening disease. Dhanwantari Nighantu contains total 703 drugs, out of these total 17 drugs having Pramehaghna (anti-diabetic) property which belongs to different Vargas. The result shows that out of 17 drugs 11 drugs are belonging from Guduchyadi varga (8.5%), 3 drugs are from Suvarnadi varga (1.42%), 2 drugs are from Chandanadi varga (2.53%), and 1 drug from Mishrakadi varga (1.21%). Some of them are useful for pittaj prameha as they are having shita virya and tikta rasa. Some are useful for kaphaj prameha because of their ushna virya. Drugs can be selected on the basis of symptoms or do shik predominance of Prameha vyadhi.

Key words: Ayurveda, Dhanvantari Nighantu, diabetes, Prameha

INTRODUCTION According to Acharya Charaka sedentary lifestyle, excessive sleep, meat soup of domestic, aquatic and marshy animals, hanvantari Nighantu is one of the curd, and other milk products or any other food material important collections of herbs with their which aggravates the kapha dosha are responsible for produce properties and synonyms in Ayurveda. Prameha vyadhi.[1-3] According to Laghu Vagbhatta foods, D th drinks or any other activities which aggravates meda, mutra, This must have been before the 11 century A. D., but some authors said that it might be between and kapha are the main cause for the genesis of Prameha.[4] 10th and 13th century A.D.[8] This nighantu is written Diabetes mellitus is not a single disease, but it is a syndrome by Mahendra Bhaugika. In this nighantu, for the first which is characterized by hyperglycemia caused by an absolute time, the drugs are classified as Aushadhi dravya or relative deficiency of insulin. It is also associated with a or on the basis of medicinal property. During this disturbance in carbohydrate, fat, and protein metabolism, which period the numbers of aushadhi dravya were many. leads to disturbance of water and electrolyte homeostasis. It was necessary to have a systematic study of these Long-term metabolic derangement is associated with structural drugs.[8] Therefore in this nighantu, the drugs are and functional changes in many organs, especially with those divided into seven varga on the basis of their action. which are the part of the vascular system, which leads to the They are as: Guduchyadi varga, Shatpushpadi complications of the diabetes mellitus. These characteristically varga, Chandanadi varga, Karviradi varga, affect the kidney (diabetic nephropathy), eyes (diabetic Amradi varga, Suvarnadi varga, and Mishrakadi retinopathy), and nervous system (diabetic neuropathy).[10] varga.[7] In Rajnighantu, Narhari Pandit uttered that a physician without the knowledge of Nighantu, We have done a study and find that 17 drugs from 7 vargas of a scholar without the knowledge of Vyakaran and Dhanvantari nighantu having Pramehaghna (anti-diabetic) a soldier without Aayudha all these three being laughed at in this world.[7] Address for correspondence: Dr. Roli Sarjuprasad Mishra, Nagarjuna Girls Hostel, | निघण्टुना विना वैद्यो विद्वान् व्याकरणं विना I.M.S., B.H.U., Varanasi - 221 005, Uttar Pradesh, अनभ्यासेन धानुष्कस्त्रयो हास्यस्य भाजनम् || India. E-mail: [email protected] (राजनिघण्ट)ु

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Table 1: Useful drugs for diabetes according to their varga Name of the Varga Total number of drugs Percentage (%) Guduchyadi Guduchi, Murva, Dhanvyaas, 11/128=8.5 Varga‑ Pratham Haridra, Daruharidra, Varga Shalparni, Gokshura, Sativa, Ashmantak, Haritaki, Aaragvadha Chandanadi Varga Ushira, Jatiphala 2/79=2.53 Suvarnadi Varga Loham, Mandura, Vaikranta 3/211=1.42 Mishrakadi Varga Triphala 1/82=1.21

Table 2: Useful drugs for diabetes with special reference Drug name Family Action of drug References Guduchi (Tinospora cordifolia Wild.) Menispermaceae Mehajita Dh. Ni. Guduchyadi Varga 6, Page no. 17 Murva (Marsdenia tenacissima W. & A.) Asclepiadaceae Mehnashini Dh. Ni. Guduchyadi Varga 13, Page no. 18 Dhanvyaas (Fagonia arabica Linn.) Zygophyllaceae Mehanashini Dh. Ni. Guduchyadi Varga 20 Page no. 19 Haridra (Curcuma longa Linn.) Zingiberaceae Mehanuta Dh. Ni. Guduchyadi Varga 55 Page no. 26 Daruharidra (Berberis aristata DC.) Berberidaceae Mehajita Dh. Ni. Guduchyadi Varga 59, Page no. 26 Shalaparni (Desmodium gangeticum. Fabaceae Mehanashini Dh. Ni. Guduchyadi Varga 88, Page DC.) no. 32 Gokshura (Tribulus terrestris Linn.) Zygophyllaceae Pramehanivartaka Dh. Ni. Guduchyadi Varga 103, Page no. 34 Sariva (Hemidesmus indicus R. Br.) Asclepiadaceae Mehanashana Dh. Ni. Guduchyadi Varga 160, Page no. 46 Ashmantaka (Ficus lacor Roxb.) Moraceae Pramehajita Dh. Ni. Guduchyadi Varga193 Page no. 51 Haritaki (Terminalia chebula Retz.) Combretaceae Mehajita Dh. Ni. Guduchyadi Varga 205, Page no. 54 Aragvadh (Cassia fistula Linn.) Fabeaceae Pramehaghna Dh. Ni. Guduchyadi Varga 216, Page no. 56 Ushira (Vetiveria zizaniodes Linn.) Graminae Mehanuta Dh. Ni. Chandanadi Varga 14, Page no. 93 Jatiphala (Myristica fragrans Houtt) Myristicaceae Mehaghna Dh. Ni. Chandanadi Varga 34, Page no. 97 Loha Pramehajita Dh. Ni. Suvarnadi Varga 28, Page no. 183 Mandura Mehanashana Dh. Ni. Suvarnadi Varga 33, Page no. 184 Vaikranta Mehajita Dh. Ni. Suvarnadi Varga 42, Page no. 186 Triphala Mehahara Dh. Ni. Mishrakadi Varga 2, Page no. 260 property [Tables 1 and 2]. Out of seven vargas, anti-diabetic having ushna virya enhance the digestive power and block drugs are present in four vargas.[5,6] the generation of kleda and aam. Characters produced by piita dosha such as burning micturition and burning Some of the above-mentioned drugs are shita in virya, sensation in palm and sole are subsided by shita virya and some of them are ushna in virya. All drugs have drugs. Drugs which are tikta in rasa and shita in virya different Rasa, Guna, Virya, and Vipaka Table 3. Drugs have a predominance of vayu and akash mahabhuta, so

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Table 3: Useful drugs for diabetes with their Guna-Karma Name of drug Rasa Guna Virya Vipaka Doshaghnata Guduchi (Tinospora cordifolia Wild.) Tikta, kashaya Guru Ushna Tridoshahar Murva (Marsdenia tenacissima W. & A.) Madhura Ushna Kapha vatashamak Dhanvyaas (Fagonia arabica Linn.) Madhura Shita Haridra (Curcuma longa Linn.) Tikta Ruksha Ushna Daruharidra (Berberis aristata DC.) Tikta Ruksha Ushna Shalaparni (Desmodium gangeticum. DC.) Tikta Guru Ushna Gokshura (Tribulus terrestris Linn.) Tridoshahar Sariva (Hemidesmus indicus R. Br.) Madhura Shita Kapha vatashamak Ashmantaka (Ficus lacor Roxb.) Madhura, Kashaya Shita Pitta kaphashamaka Jatiphala (Myristica fragrans Houtt.) Kashaya, Katu Ushna Haritaki (Terminalia chebula Retz.) Panchrasa Tridoshahar (Lavanavarjit, Kashayapradhana) Aragvadh (Cassia fistula Linn.) Tikta Guru Ushna Tridoshahar Ushira (Vetiveria zizaniodes Linn.) Tikta Shita Pittshamaka Loha Tikta Ruksha Ushna Kapha Pittasamak Mandura Vaikranta Triphala Tridoshahar

Table 4: Some previously done research works which prove the anti-diabetic effect of drugs of Dhanvantari Nighantu Name of drug Physiological activity of drug References Guduchi (Tinospora cordifolia Wild.) Antihyperglycemic, antioxidant, Sharma R. Antidiabetic claims hepatoprotective of Tinospora cordifolia (Wild.) Miers: Critical appraisal and role in therapy. Asian Pac J Trop Biomed 2015;5:68‑78. Murva (Marsdenia tenacissima W. Hypoglycemic activity Nayak A. In‑vitro hypoglycemic & A.) activity evaluation of Marsdenia tenacissima and Sphaeranthus indicus, inventi rapid. Ethnopharmacology 2014;3:1‑4. Dhanvyaasa (Fagonia arabica Hypoglycemia Chourasia SR. Effect of aqueous Linn.) extract and fraction of Fagonia arabica on in vitro anticoagulant activity. Clin Appl Thrmb Hemos 2013;20:844‑50. Haridra (Curcuma longa Linn.) Anti‑diabetic, antioxidant, Krup V. Pharmacological activities hepatoprotective of turmeric (Curcuma longa Linn.): A review. J Trad Med Clin Naturopathy 2015;2:2167‑1206. Daruharidra (Berberis aristata DC.) Hypoglycemic, Antioxident, Komal S. Berberis aristata: A review. Hepatoprotective Int J Res Ayurveda Pharm 2011;2:383‑8. Shalaparni (Desmodium Antidiabetic activity Govindarajan R, Asare‑Anane H, gangeticum. DC.) Persaud S, Jones P, Houghton PJ. Effect of Desmodium gangeticum extract on blood glucose in rats on insulin secretion in vitro. Planta Med 2007;73:427‑32. (contd...)

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Table 4: (Continued) Name of drug Physiological activity of drug References Gokshura (Tribulus terrestris Linn.) Anti‑hyperglycemic activity El‑Shaibany A. Antihyperglycemic activity of Tribulus terrestris L A ERIAL part extract in glucose‑loaded normal rabbit. Trop J Pharm Res 2015;14:2263‑8. Sariva (Hemidesmus indicus R. Br.) Hypoglycaemic activity Gayathri M, Kannabiran K. Hypoglycemic activity of Hemidesmus indicus R. Br. on streptozotocin‑induced diabetic rat. Int J Diabetes Dev Countries 2008;28:6‑10. Haritaki (Terminalia chebula Retz.) Anti‑diabetic activity Kumar GP. Anti‑diabetic activity of fruits of Terminalia chebula on streptozotocin‑induced diabetic rat. J Health Sci 2006;52:283‑91. Aragvadh (Cassia fistula Linn.) Anti‑diabetic activity Joshi T. Anti‑diabetic and other pharmacological activities of Cassia fistula Linn. Int J Adv Technol Eng Sci 2016;4. Ushira (Vetiveria zizaniodes Linn.) Antihyperglycaemic effect Karan SK. Antihyperglycaemic effect of Vetiveria zizaniodes Linn. Nash root extract in alloxan‑induced diabetic rats. Asian J Chem 2013;25:1555‑7. Triphala Anti‑diabetic activity Hamid KS. A systematic review of the antioxidant, anti‑diabetic and anti‑obesity effects and safety of triphala herbal formulation. J Med Plants Res 2013;7:831‑44. they absorb the kleda of the body by these properties. which belongs to different Vargas. The result shows that Tikta rasa has also property of sukshmasrotogamitva so out of 17 drugs 11 drugs are belonging from Guduchyadi they can purify the srotas or microchannels. Because varga (8.5%), 3 drugs are from Suwvrnadi varga (1.42%), of these properties above mention drugs can break the 2 drugs are from Chandanadi varga (2.53%), and 1 drug samprapti (pathogenesis) of Prameha. from Mishrakadi varga (1.21%). We have mentioned some previously done research works which prove the anti-diabetic effect of drugs of Dhanvantari Nighantu in Table 4. Samprapti[2,3,9] Hetu, Linga (symptoms), and Aushadh are the three important pillars for treatment of any disease among them. Aushadh dravyas are the key element of Dhanvantary nighantu. Aushadh dravyas are 1st time accepted in Dhanvantari nighantu by Mahendra Bhaugika. Out of 7 Vargas, four Vargas and from 703 drugs only 17 drugs having Pramehaghna (anti-diabetic) property. The result of this study is very beneficial to treat Prameha as we can achieve the best result in treating Prameha only when we know about the different types of Prameha. From that point of view in Dhanvantari nighantu, the drugs have described in very systematic manner. Hence, our study can give a great help to treat Prameha in respect to different types. By Dhanvantari nighantu describes seven Vargas. Drugs of these drugs, we can make a formulation for the treatment Dhanvantari nighantu are studied for their Pramehaghna of Prameha (diabetes) either it may be pittaj prameha or property. A total of 17 drugs are having anti-diabetic property kaphaj prameha. Some drugs are shita in virya, and some

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S133 Mishra, et al.: Management of diabetes ascribed by Dhanvantari Nighantu drugs are ushna in virya. Drugs can be chosen on the basis Chaukhambha Prakashana; 2015. p. 344-50. of symptoms and doshik predominance. 5. Bhaugika M. In: Sharma PV, editor. Dhanvantari Nighantu. Translated by Dr. Guruprasad Sharma. Reprint ed. Varanasi: Chaukhambha Orientalia; 1982. REFERENCES 6. Bhaugika M. In: Kamat SD, editor. Dhanvantari Nighantu. Reprint ed. New Delhi: Chaukhambha 1. Agnivesha. In: Pandey K, Nath G, editor. Chaturvedi Sanskrit Pratishthan; 2004. Charaka, Dridhabala. Charak Samhita, Nidan Sthsna. 7. Vigyana D. Prof. P. V. Sharma, Preface by Pranacharya Prameha Nidan Adhyaya. Reprint ed. Varanasi: Govardhana Sharma Changani. Reprint ed. Varanasi: Chaukhambha Bharati Acdamy; 2012. p. 630-41. Chaukhambha Bharati Acadamy; 2008. p. 142-3. 2. Agnivesha. In: Pandey K, Nath G, editor. Chaturvedi 8. Vigyana D. Prof. D. Shant Kumar Lucas. Reprint edition. Charaka, Dridhabala. Charak Samhita, Chikitsa Sthsna, Varanasi: Chaukhambha Vishvabharti; 2006. p. 423-4. Prameha Chikitsa Adhyaya. Reprint ed. Varanasi: 9. Byadgi PS, Pandey AK. A Text Book of Kayachikitsa. Chaukhambha Bharati Acdamy; 2012. p. 227-47. Reprint edition. New Delhi: Chaukhambha Publication; 3. Sushruta. In: Sharma AR, editor. Chandrata. Sushrut 2014. p. 684-6. Samhita, Nidan Sthana, Prameha Nidan Adhyaya. 10. Colledge NR, Walker BR, Stuart H. Ralston Davidson’s Reprint ed. Varanasi: Chaukhambha Surbharati Principles and Practice of Medicine. UK: Elsevier; 2010. Prakashana; 2001. p. 502-8. p. 798. 4. Vagbhatta L, Hridaya A. In: Gupta KA, editor. Nidana Sthana, Prameha Nidana Adhyaya. Reprint ed. Varanasi: Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S134 Evaluation of tongue W.R.T agni

Ruby Kumari Singh, Yogendra Kumar, Priyadarshini Tewari Department of Vikriti Vigyan, I.M.S, B.H.U, Varanasi, Uttar Pradesh, India

Abstract

Jivha pariksha (tongue examination) is one of the means for diagnosis of disease and assessment of Agni. Aasthasthana Neerikshan (eight folds of examinations) is mentioned by Yogaratnakara for rogi pariksha in the late 17th century, which includes nadi, mala, mutra, jivha, shabdha, Sparsha, Drik, and Aakriti, it is also mentioned in Yoga-tarangini. It is said that different areas of the tongue are allocated for different organs of the body and tongue coating extension and thickness reveals the pathology in the digestive systems. It is said in Ayurvedic texts that every disease is formed due to mandagni and that mandagni leads to the formation of excess kitta bhag reflected on the tongue. Our aim is to assess the Agni as per the Ayurvedic Criteria and to study jihva pariksha in healthy volunteers to fulfill our hypothesis whether tongue characteristics have any relationship with Agni. For the study, ORIGINAL ARTICLE ORIGINAL 25 healthy volunteers were registered (BAMS and BNYS) from Ayurvedic wing, Faculty of Ayurveda, Institute of Medical Sciences, BHU. We have used HTC one M8, IMEI-SV 01, 16 megapixel cameras to capture the image of the tongue under natural light to see color, coating, fissure on tongue, pH paper to assess pH of the tongue, and filter paper to assess wetness of tongue. Assessment of Agni on the basis of questionnaire prepared for the study.

Key words: Agni, fissure, Jivha, pH, tongue

INTRODUCTION One dies if this fire is extinguished, lives long if it functions properly; hence, Agni is the root cause of all.[12] It has been arious folds of examinations are stated that Agni cooks the food. It is of four kinds, namely, one mentioned in Ayurveda texts for the physiological (not vitiated with the doshas) and three other diagnosis of diseases, i.e., Trividha are pathological.[13] Samagni (physiological) is assessed based V[1] [2] on three factors, namely, Jarana Shakti (Digestion power), pariksa, Chaturvidha pariksa, Panchvidha Pariksa-Nidana, Purvarupa, Rupa, Upasaya, Ruchi (Appetite), and Abhyavaharana shakti (Hunger),[14] and Samprapti,[3] Saptavidha Pariksha-Prashna pathological Agni assessed on the basis of questionnaire for [15] +Panchindriya Pariksha,[4] Aasthasthana Agni assessment. Prakriti - the body constitution is assessed [16] neerikshan,[5] Dashavidha pariksha,[6] and on the basis of questionnaire. Dwadasha pariksa.[7] Among these Aasthasthana Neerikshan is one mentioned in Yogaratnakara for Aims and Objectives rogi pariksha which includes nadi, mala, mutra, jihva, shabdha, sparsha, Drik, and Aakriti.[8] The We hypothesized whether the tongue characteristics (color, tongue is one of the ways to see the changes taking size, shape, coating, fissure, and moisture) are influenced by place in the basic constituents of the body and to the effect of Agni and relation of prakriti with jihva. monitor the progress of the disease. It also reveals the prakriti and vikruti of the tongue through its color, size, shape, coating, fissure, and moisture. Our Purpose Acharya Yogaratnakar has explained that in vata 1. To assess the prakriti of the individuals as per the Dosha prakopa, jihva become sheeta, Khara, and Ayurvedic criteria. sphutita; in pitta Dosha prakopa, jihva become 2. To assess the Agni of the individuals as per the Ayurvedic rakta and shyama varna; in Kapha Dosha prakopa, criteria. shweta and pichhila; in Sannipataj Dosha, jihva 3. To study Jihva pariksha in healthy individuals. become Krishna, sakantak, shushka, and mixed lakshana of all doshas are found in dwandaja Address for correspondence: Dosha prakopa.[9] It is also mentioned in Yoga- Ruby Kumari Singh, Department of Vikriti Vigyan, I.M.S, tarangini,[10] Sharangdhar Samhita.[11] Lifespan, B.H.U, Varanasi, Uttar Pradesh, India. complexion, strength, health, enthusiasm, Phone: +91-9453494143. E-mail: [email protected] immunity, etc., depend on Agni (body fire).

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S135 Singh, et al.: Evaluation of tongue features with relation to agni status

MATERIALS AND METHODS CONCLUSION

For this study, 25 healthy individuals were registered (BAMS • We have registered 25 healthy individuals, out of which and BNYS students) from Faculty of Ayurveda, IMS, BHU. 13 are male and 12 are female. We have used HTC one M8, 16 megapixel cameras to capture • Of 13 male candidates, 16 % were of PK prakriti followed the image of the tongue, and also to see the size, shape, by 12% of VP prakriti. Of 12 female candidates, 28% coating, fissure, and moisture of the tongue. We have used were of PK prakriti followed by 12% of KP prakriti. filter paper to assess the moisture of the tongue; pH paper to • Of 25 cases, maximum number, i.e., 16% were found check pH of the tongue.[17] to have samagni followed by 12% with mandagni and tikshnagni. • On examination of the tongue, 20 cases have normal Methods pattern of tongue, 2 have small tongue, and 3 have large tongue. Of 25 cases, in shape, 80% individuals have U After proper rinsing of the mouth, the tongue was examined shape of tongue and 20% have V shape of tongue. In in natural light. In sitting position, individual was asked to protrude out the tongue and image captured within a minute [18] before scrapping of the tongue. Table 4: Tongue examination in healthy individuals, (n=25) We had examined the dorsal, ventral and lateral surface of Features Number of cases (%) tongue for colour, coating, fissure, vein engorgement of the tongue. Color Pale 3 (12) Pink 12 (48) OBSERVATIONS AND RESULTS Dark pink 10 (40) Size The study was conducted in Ayurvedic wings of S.S.H, IMS, BHU. Normal 20 (80) Thin 2 (8) Thick 3 (12) Table 1: According to sex of the individuals, (n=25) Shape Sex Number of cases (%) U shape 20 (80) M 13 (52) V shape 5 (20) F 12 (48) Coating Present 8 (32) According to Prakriti of the Table 2: Absent 17 (68) individuals, (n=25) pH Type of prakriti Number of cases Acidic (6.5) 5 (20) M (%) F (%) Alkaline (7–8) 20 (80) VP 3 (12) 1 (4) Moisture PK 4 (16) 7 (25) Normal 20 (80) KV 1 (4) 0 (0) Dry 5 (20) PV 2 (8) 1 (4) KP 2 (8) 3 (12) VK 1 (4) 0 (0) Table 5: Type of tongue according to dosha, (n=25) Doshic tongue Number of cases (%) Table 3: Status of Agni among healthy Vataja 0 (0) individuals, (n=25) Pittaja 5 (20) Nature of Agni Number of cases (%) Kaphaja 2 (8) Samagni 16 (64) Sannipataja 4 (4) Mandagni 3 (12) Dwandaja 14 (56) Visamagni 2 (8) VP 4 (28) Tikshnagni 3 (12) PK 7 (50) Atyagni 1 (4) KV 3 (21)

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S136 Singh, et al.: Evaluation of tongue features with relation to agni status

a b

Figure 1: Tongue on the basis of color, (a) pink tongue, a b (b) pale tongue Figure 5: Tongue on the basis of shape, (a) kaphaja jihva, (b) sannipataja jihva

a b a b Figure 6: (a) U shape, (b) V shape Figure 2: Tongue on the basis of coating, (a) thick yellow coating, (b) thin yellow coating • All the above finding, may give a conclusion that, dwandaja prakriti person can have samagni and dwandaja dosha prakopak jihva.

REFERENCES

1. Lochan K. Astangahrdayam, Vagbhatta, Commentary Sarvangasundara of Arunadatta and Ayurvedarasayan of Hemadri, Sutrasthana. Ch. 1, Slokas 21. Varanasi: a b Chaukhambha Orientalia; 2007. Figure 3: Tongue on the basis of size, (a) small tongue, 2. Kasinath S. Charak Samhita, Revised by Charak (b) large tongue and Drdhabla, Ayurveda Dipika Commentary of Chakrapanidutta with Vidyotini Hindi Commentary. Ch. 11, Slokas 17 edited by Dr, Gangasahay Pandey, Sutrasthana Varanasi: Chaukhambha Sanskrit Sansthana; 2013. 3. Upadhyaya Y, Madhava Nidanam with Madhukosha Commentary, Edited with Vidyotini Hindi commentary, Vol. 1. Ch. 1, Slokas. 4, Varanasi: Publication Chaukhambha Prakashan; 2018. 4. Ambikadutta S. Sushruta Samhita, Hindi Commentary. Sutra Sthana, Ch. 10, Slokas. 4. Varanasi: Chaukhamba a b Prakashanam; 2009. Figure 4: Tongue on the basis of doshas, (a) vataja jihva, 5. Laksmipati SV. Yogaratnakara with Vidyotini Hindi (b) pittaja jihva Commentary, Pub. Purvartha, Jihva Pariksa. Varanasi: Chaukhambha Prakashan; 2009. p. 15. color, 48% have pink color tongue. In coating, 68% have 6. Kasinath S. In: Pandey G, Samhita VC, editor. Revised no coating on tongue. In pH, 80% cases have alkaline by Charak and Drdhabla, Ayurveda Dipika Commentary range of pH. of Chakrapanidutta with Vidyotini Hindi Commentary. • Of 25 cases, 56% individuals have dwandaja jihva, of Ch. 8, Slokas. 94. Varanasi: Chaukhambha Sanskrit which 50% have pittaj-kaphaja jihva. Sansthana; 2013.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S137 Singh, et al.: Evaluation of tongue features with relation to agni status

7. Ambikadutta S. Sushruta Samhita, Hindi Commentary. 14. Upadhyaya Y. Madhava Nidanam with Madhukosha Sutra Sthana, Ch. 35, Slokas 3. Varanasi: Chaukhamba commentary, edited with Vidyotini Hindi commentary. Prakashanam; 2009. Vol. 2. Ch. 33, Slokas 5. Varanasi: Publication 8. Nirmal S. Yogatarangini of Trimala Bhatt. Ch. 13/5-6. Chaukhambha Prakashan; 2014. Varanasi, India: Chaukhambha Sanskrit Bhawan; 2007. 15. Murthy KR. Srikantha, Susruta Samhita, English p. 73. Translation. Sutrasthana. Vol. 1. Ch. 35, Slokas. 24-25. 9. Brahmanand T, Samhita S. Dipika Hindi Commentary. Varanasi: Chaukhambha Orientalia; 2008. Varanasi: Chaukhamba Sanskrit Bhawan. Ch. 3, Slokas 16. Baghel MS, Rajagopal. Developing Guidelines for 14-15, Purvakhand. Varanasi: Chaukhambha Prakashan; Clinical Research Methodology on Ayurved, WHO DFC 2006. p. 41. Sponsored; 2011. 10. Sharma PV. Caraka-Samhita, English Translation. 17. Babu NA, Masthan KM, Bhattacharjee T, Elumalai M. Chikitsasthana. Vol. 2. Ch. 15, Slokas 3-4. Varanasi: Saliva-the key regulator of oral changes in diabetes Chaukhambha Orientalia; 2008. patients. Int J Pharm Sci Res 2014;5:2579-83. 11. Murthy KR. Srikantha, Susruta Samhita, English 18. Tadaaki K, Kamarudin ND, Ooi CY, Kobayashi F, Mi X, Translation. Vol. 1. Sutrasthana, Ch. 35, Slokas 24. Sekine M, Wakasugi A, et al. Quantification of tongue Varanasi: Chaukhambha Orientalia; 2010. colour using machine learning in Kampo medicine, 12. Baghel MS, Rajagopal. Developing Guidelines for Japan. Eur J Integr Med 2016;8:932-41. Clinical Research Methodology in Ayurved. WHO DFC 19. Zhang B, Wang X, You J, Zhang D. Tongue color analysis Sponsored; 2011. for medical application. Evid Based Complement Altern 13. Ambikadutta S. Sushruta Samhita, Hindi commentary. Med 2013;2013:11. Sharir Sthana, Ch. 4, Slokas 27. Varanasi: Chaukhamba Prakashanam; 2009. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S138 Medicinal Herbs: An epitome towards treatment of Prameha (Diabetes)

Sadhana Singh, Rashmi Yadav, Aparana Dixit, Roli Sarjuprasad Mishra, Priyanka Gautam Department of Dravyaguna, I.M.S, B.H.U, Varanasi, Uttar Pradesh, India

ABSTRACT

India has a high prevalence of diabetes and the number is increasing at an alarming rate. The most disturbing trend is the shift in age of onset of diabetes to a younger age in the recent years. This could have long-lasting adverse effects on nation’s health and economy. Being a Dravyaguna (Ayurveda) Scholar, it is our primary duty to explore such plants along with references and their properties mentioned in classics, i.e., Rasa (taste), Guna (physical/

REVIEW ARTICLE REVIEW chemical property), Virya (potency), and Vipaka (metabolism), and probable mode of action of these medicinal plants based on their rasa panchaka (rasa, guna, virya, vipaka,and prabhava) is also concluded. Prameha has grave and serious clinical manifestations with the possibility of occurrence of serious complications and at times with fatal prognosis. Therefore, in the present study, an attempt has been made to explore the possibility of a better control over diabetes by medicinal plants.

Key words: Diabetes, Guna, Prabhava, Prameha, Rasa, Vipaka, Virya

INTRODUCTION DISCUSSION

s Prameha (diabetes) is not merely a Madhumeha has been described as one among the 20 types of metabolic syndrome, it gives rise to prameha and is subtype of Vataja prameha.[5] It is tridoshaja Afatal complications too. That is why vyadhi. Abadha shleshma is particular dosha in all types of health authorities all over the world and in all prameha. The clinical entity in which patient voids the urine countries are trying their best to make a control having concordance with madhu, i.e. kashaya and madhura over the spread of this disease. taste, ruksha texture, and madhu (honey)-like color, and body acquires sweetness is called madhumeha.[6] Treatment of Nidana of Prameha (etiology of diabetes in madhumeha is difficult due to contradictory treatment of vata ayurveda) -Asyasukham (comfortable sitting, (predominant dosha) and meda (predominant dushya). Drugs i.e., sedentary lifestyle and lack of physical which combate vata will increase meda and kapha and vice activity and exercise), Svapnasukham (comforts versa. In avaranajanya madhumeha, the treatment must be of sleeping and excess sleeping), Dadheeni such that should not vitiate vata and should clear avarana also. (excessive consumption of Curds and its preparations), Gramya-oudaka-anupa mamsa Most of the plants have kashaya, katu, tiktain rasa, ruksha (meat of animal living in water and marshy in guna, and ushna in virya. It also has tridoshashamaka regions), Payamsi (excessive consumption of action which is desirable in treatment of madhumeha. The milk, its derivatives, and preparations), Nava-anna plants having of tikta and katu rasa alleviate meda and kapha panam (food, drinks, and dishes made from new main etiological factors involved in pathogenesis of disease. grains, etc.,), Guda Vaikruti (jaggery), and Kapha Tikta Rasa contains vayu and akasha due to which it attains kricha sarvam (all foods and lifestyle activity specific property Sukshma-Srotogamitva, and consequently, which increase Kapha) are etiology of Prameha.[1] Sroto-rodha is counteracted through it.

Being ushna virya, it pacifies vata, and by virtue of kashaya SAMPRAPTI OF PRAMEHA rasa, it reduces Sariragata kleda. The shita virya drugs act on (PATHOPHYSIOLOGY OF DIABETES Pittaja Prameha, and it pacifies burning sensation in limbs IN AYURVEDA) Address for correspondence: Dr. Sadhana Singh, Departmentof Dravaguna, When Basti is vitiated with the Meda (Fat), Faculty of Ayurveda, IMS, BHU, Varanasi, Pin-221005 U.P. Masa (Flesh), Shareera kleda (fluid of the body) E-mail: [email protected] and Kapha causes prameha.[2]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S139 Singh, et al.: Miraculous Herbs for Prameha ( Diabetes) (Contd...) [3,4] Reference Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No.759 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 277 Bhavaprakash Nighantu, Haritakyadi Varga - Sloka No. 42, page No. 12 Bhavaprakash Nighantu, Haritakyadi Varga - Sloka No. 63, page No. 18 Bhavaprakash Nighantu, Haritakyadi Varga - Sloka No. 42, page No. 58 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 441 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 800 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 175 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 75 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 761 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 632 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 242 Dosa Karma Tridoshahara Vata, Shleshmahara Kapha, Pittaghna Kaphahara Kaphavardhaka vatapittshamaka Kaphapittahara Kaph - Pittashamaka Kaph - Vatashamaka Kaph - Vatashamaka Tridoshahara Vata - Pitta Shamaka Kapha, Pitta Shamak Vipaka Madhura Madhura - - - Katu Katu Katu Katu Madhura Madhura Katu Virya Shita Anushnashita - - Shita Shita Ushna Ushna Ushna Ushna Shita Shita Guna Guru, Ruksha, Shita Laghu, Snigdha, Tikshana - - - Ruksha, Laghu Guru, Ruksha Ruksha, Laghu Laghu, Snigdha Guru, Snigdha Guru, Snigdha Ruksha, Laghu Guna karma of pramehahara plants dravya - guna vigyana Table 1: Rasa Pancharasa Katu - - - Tikta Tikta, Kashaya, Madhura Katu, Tikta Tikta Tikta, Kashaya Madhura Tikta, Kashaya Linn.) Nees.) Willd.) Linn.) Gaertn.) Royle. Ex Benth) Loud.) Linn.) Linn.) Tribulus terrestris Adhatoda vasica Emblica officinalis Piper longum Picrorhiza kurroa Rubia cordifolia Psoralea corylifolia Tinospora cordifolia Plant name Amalaki ( Family - .Euphorbiaceae Pippali ( Family - Piperaceae Triphala Trikatu Ashtavarga Katuki ( Family - Scrophulariaceae Manjistha ( Family - Rubiaceae Bakuchi ( Family - Fabaceae Devadaru (Cedrus deodara Family - Pinaceae Guduchi ( Family - Menispermaceae Gokshura ( Family - Zygophyllaceae Vasa ( Family - Acanthaceae

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S140 Singh, et al.: Miraculous Herbs for Prameha ( Diabetes) (Contd...) [3,4] Reference Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 149 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 528 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 736 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 699 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 540 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 103 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 256 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 671 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 195 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 682 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 159 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 676 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 661 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 707 Dosa Karma Kapha - Pitta shamaka Vata pitta Kapha shamaka Vata pitta Tridoshahara Tridoshaghni Kapha - vata shamaka Vata - pitta shamaka, Pitta - kapha shamaka Kapha - pitta shamaka Kapha - pitta shamaka Kapha - pitta shamaka Kapha - pitta shamaka Kapha Pitta shamaka Kapha Vata shamaka, Pitta shodhaka Vipaka Katu Katu Madhura Katu Katu Katu Madhura Katu Katu Katu Katu Katu Katu Katu (Continued)

Virya Shita Ushna (Ishat) Shita Ushna Anushna Ushna Shita Shita Shita Shita Shita Shita shita Ushna Table 1: Guna Laghu Laghu, Ruksha Laghu, Snigdha, Pichchhila Guru, Ruksha Laghu, Snigdha Ruksha, Laghu Laghu, Snigdha Ruksha Laghu, Ruksha Ruksha, Laghu Ruksha, Laghu Laghu, Ruksha Laghu, Ruksha Guru, Ruksha Tikshna Rasa Tikta, Kashaya Katu Madhura Tikta, Kashaya Tikta Tikta, Kashaya Tikta, Madhura Kashaya Kashaya Tikta, Kashaya Tikta, Kashaya Kashaya Kashaya Katu

Linn.) Roxb.) Roxb.) Linn.) Willd.) Gaertn.) Wall.) Mangifera spreng.) A. Juss) Linn.) Gymnema sylvestre Melia azedarach Pterocarpus marsupium Marsdenia tenacissima Ougeinia oojeinensis (Acacia catechu Abutilon indicum Terminalia arjuna Shorea robusta Linn.) Azadirachta indica Solanum nigrum Onosma bracteatum Leucas cephalotes Plant name Nimba ( Family - Meliaceae Mahanimba ( Family - Meliaceae Atibala ( Family - Malvaceae Moorva ( W. & A.) Family - Asclepiadaceae Kakamachi ( Family - Solanaceae Meshashringi R.Br. Family - Asclepiadaceae Gojihva ( Family - Boraginaecae Shala ( Family - Dipterocarpaceae Arjuna ( Family - Combretaceae Beejaka ( Roxb.) Family - Fabaceae Khadira Family - Mimosoideae Tinisha ( Family - Fabaceae Aamra Beeja Majja ( indica Family - Anacardiaceae Dronapuspi ( Family - Labiatae

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S141 Singh, et al.: Miraculous Herbs for Prameha ( Diabetes) (Contd...) [3,4] Reference Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 684 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 740 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 3 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 6 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 816 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 674 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 753 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 521 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 651 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 776 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 190 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 674 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 575 Dosa Karma Kapha - pitta shamaka Tridoshahara Kapha - pitta shamaka Kapha - vata shamak Kapha - pitta shamaka Kapha - pitta shamaka Tridoshahara Kapha Vata shamaka Tridoshashamaka Kaph - vata shamaka Kapha - pitta shamaka Kapha - pitta shamaka Kaph - vata shamaka Vipaka Katu Katu Madhura Katu Katu Katu Madhura Katu Katu Madhura Katu Katu Katu (Continued)

Virya Ushna ushna Shita ushna ushna Shita Ushna Ushna Shita Usna Shita Shita Ushna Table 1: Guna Laghu, Ruksha Laghu, Sinagdha Laghu, Laghu, Laghu, Ruksha Laghu, Ruksha Laghu, Ruksha Laghu, Ruksha, Tikshna Laghu, Snigdha, Tikshna Laghu, Snigdha Ruksha, Laghu Laghu, Ruksha Laghu, Tikshna Rasa Tikta, Katu Tikta, Katu, Madhura Tikta, Tikta, Tikta, Kashaya Kashaya Pancharasa Katu Kashaya, Tikta Katu, Tikta, Kashaya Kashaya Kashaya Kashaya, Tikta, Katu

Retz.)

linn.) Wall.) Holoptelia Linn.) Linn.) Bergenia ligulata Dioscorea bulbifera Argyreia speciosa Momordica charantia Mallotus philippinensis Myrica esculenta planch. ) Diospyros peregrina Terminalia chebula Vateria indica Centella asiatica Bacopa monnieri Anogeissus latifolia Plant name Karavellam ( Linn.) Family - Cucurbitaceae Varahikanda ( Linn.) Family - Dioscoreaceae Mandukaparni ( Family - Apiaceae Brahmi ( Family - Scrophulariaceae Chirbilva (karanji) ( integrifolia Family - Ulmaceae Dhava ( Family - Combretaceae Haritaki ( Family - Combretaceae Kampillaka ( Muell. Arg.) Family - Euphorbiaceae Pashanabheda ( (Wall.) Engl.) Family - Saxifragaceae Vriddhadaru ( Sweet.) Family - Convolvulaceae Tinduka ( Gaertn.) Family - Ebenaceae Sarja ( Family - Dipterocarpaceae Kataphala ( Buch - Ham.) Family - Myricaceae

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S142 Singh, et al.: Miraculous Herbs for Prameha ( Diabetes) [3,4] Reference Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 54 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 506 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 144 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 806 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 664 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 666 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 668 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 670 Dravya - Guna Vigyan Vol 2, Prof. P.V. Sharma, Page No. 680 Dosa Karma Tridoshahara Kaph - vata shamaka Kaph - vata shamaka, Pitta vardhaka Tridoshashamaka Kapha - pitta shamaka Kapha - pitta shamaka Kapha - pitta shamaka Kapha - pitta shamaka Kapha - pitta shamaka Vipaka Katu Katu Katu Katu Katu Katu Katu Katu Katu (Continued)

Virya Ushna Ushna Ushna Ushna Shita Shita Shita Shita Shita Table 1: Guna Laghu, Ruksha, Tikshna, sukshma, sara Laghu, Ruksha Laghu, Tikshna Laghu, Ruksha Guru, Ruksha Guru, Ruksha Guru, Ruksha Guru, Ruksha Laghu, Ruksha Rasa Tikta, Katu Tikta, Katu, Kashaya Tikta, Katu, Kashaya Tikta, Katu, Kashaya Kashaya Kashaya Madhura, Kashaya Kashaya Kashaya

Lam.) Hook Linn.) Linn.) Roxb.) Pongamia pinnata Thespesia populnea Ficus religiosa Butea monosperma Commiphora mukul Ficus benghalensis Dalbergia sissoo Plant name Guggulu ex stocks.) Burseraceae Palasha ( Family - Fabaceae Karanja Phala ( Pierre) Family - Fabaceae Shinshapa ( Family - Fabaceae Vata ( Family - Moraceae Udumbara (Ficus glomerata Roxb.) Family - Moraceae Ashvatha ( Family - Moraceae Plaksha (Ficus lacor Buch. - Ham.) Family - Moraceae Pareesha ( Soland.) Family - Malvaceae

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S143 Singh, et al.: Miraculous Herbs for Prameha ( Diabetes)

Table 2: Pramehahar drugs in Bhavaprakash Nighantuof herbal origin with respective references Sanskrit name Guna Karma Reference of Varga and Shloka no. in Bhavaprakash Nighantu[4] Aamalaki (Emblica officinalis Gaertn.) Pramehaghna Haritkyadi Varga‑39 Page No. 10 Arkapuspi (Holostemma annularis K. Schum.) Mehajeet Guduchyadi Varga‑271 Page No. 441 Ashtavarga Mehapranut Haritkyadi Varga‑122 Page No. 58 Atibala (Abutilon indicum Linn.) Mehasamana Guduchyadi Varga‑146 Page No. 352 Bakuchi (Psoralea corylifolia Linn.) Mehanut Haritkyadi Varga‑208 Page No. 119 Beejaka (Pterocarpus marsupium Roxb.) Mehaghna Vatadi Varga‑29 Page No. 512 Brahmi (Bacopa monnieri Linn.) Mehajeet Guduchyadi Varga‑281, Page No. 446 Chirbilva (Holoptelia integrifolia planch.) Pramehajeet Guduchyadi Varga‑124, Page No. 338 Devadaru (Cedrus deodara Loud.) Pramehanuta Karpuradi Varga‑25, Page No. 186 Dhava (Anogiessus latifolia Wall.) Pramehahara Vatadi Varga‑60, Page No. 527 Dronapuspi (Leucas cephalotes spreng.) Mehahara Shaka Varg‑34, Page No. 662 Gojihva (Onosma bracteatum Wall.) Pramehara Guduchyadi Varga‑298, Page No. 456 Guduchi (Tinospora cordifolia Willd.) Pramehanut Guduchyadi Varga‑10, Page No. 257 Guggulu (Commiphora mukul Hook ex stocks.) Mehahara Karpuradi Varga‑40, Page No. 195 Gokshura (Tribulus terrestris Linn.) Pramenuta Guduchyadi Varga‑46, Page No. 279 Haridra (Curcuma longa Linn.) Mehaghna Haritkyadi Varga‑197 , Page No. 111 Haritaki (Terminalia chebula Retz.) Pramehahara Haritkyadi Varga‑20, Page No. 5 Indrayana (Citrullus colocynthis Schrad.) Pramehahara Guduchyadi Varg‑206, Page No. 389 Kadali (Pakwa) Mehaghna Amradiphala Varga‑34, Page No. 545 Kakamachi (Solanum nigrum Linn.) Mehajeet Guduchyadi Varga‑247, Page No. 423 Arjuna (Terminalia arjuna Roxb.) Mehahara Vatadi Varga‑27, Page No. 511 Kampillaka (Mallotus philippinensis Muell. Arg.) Mehanut Haritkyadi Varga‑147, Page No. 64 Karanja Phala (Pongamia pinnata Pierre) Mehajeet Guduchyadi Varga‑122, Page No. 335 Karavellam (Momordica charantia Linn.) Mehaghna Shaka Varga‑63, Page No. 670 Katabhi (Carea arborea Roxb.) Pramehara Vatadi Varga‑67 Page no.‑531 Kataphala (Myrica esculenta Buch‑Ham.) Pramehara Haritkyadi Varga‑181, Page No. 97 Katuki (Picrorhiza kurroa Royle. Ex Benth) Pramehanuta Haritkyadi Varga‑152, Page No. 67 Khadira (Acacia catechu Willd.) Mehaghna Vatadi Varga‑32 Page No. 513 Mahanimba (Melia azedarach Linn.) Pramehahara Guduchyadi Varga‑99 Page no.‑317 Mandukaparni (Centella asiatica Linn.) Mehaghna Guduchyadi Varga‑281 Page No. 446 Manjistha (Rubia cordifolia Linn) Mehanuta Haritkyadi Varga‑191 Page no.‑107 Meshashringi (Gymnema sylvestre R.Br) Mehaghna Guduchyadi Varga‑255 Page no.‑428 Moorva (Marsdenia tenacissima W. and A.) Mehanut Guduchyadi Varga‑245 Page no.‑419 Nimba (Azadirachta indica A. Juss) Mehanut Guduchyadi Varga‑96 Page no.‑314 Palasha ( Butea monosperma Lam.) Mehaghna Vatadi Varga‑53Page no. 524 Pashanabheda (Bergenia ligualata (Wall.) Engl.) Pramehara Haritkyadi Varga‑185 Page No. 101 Pippali (Piper longum Linn.) Pramehaghna Haritkyadi Varga‑55 Page No. 15 Shitivara (Marsilea minuta Linn.) Mehapranut Shaka Varga‑ 32 Page No. 661 Tinduka (Diospyros peregrina Gaertn.) Pramehaghna Aamradi phalavarga‑65 Page No. 555 Tinisha (Ougeinia oojeinensis Roxb.) Pramehajeet Vatadi Varga‑76 page No. 535 Trikatu Mehahara Haritkyadi Varga‑63 Page No. 18 Triphala Mehahara Haritkyadi Varga‑43 Page no.‑12 Varahikanda (Dioscorea bulbifera Linn.) Mehaghna GuduchyadiVarga‑179 Page No. 372 Vasa (Adhatoda vasica Nees.) Mehaghna Guduchyadi Varga‑90 Page No. 306 Vridhdaruka (Argyreia speciose Sweet.) Mehapranuta Guduchyadi Varga‑2 Page No. 394

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Table 3: Previous researches related to diabetes and plants act on diabetes Name of the drug Reported References pharmacological activity Amalaki (Emblica officinalis Gaertn.) Antidiabetic effect Santhi Sri KV, Kumari DJ, Sivannarayana G. Effect of Amla, an approach toward the control of diabetes mellitus. Int J Curr Microbiol Appl Sci 2013;2:103‑8.[5] Chirbilva (Holoptelia Interifolia Planch.) Antidiabetic effect Nath S, Sharma P, Dwivedi KN. Experimental Study on Holoptelia Interifolia planch. in relation to diabetes mellitus Type 2. Int J Pharm Res Rev 2015;4:21‑5.[6] Dhava (Anogiessus latifolia Wall.) Antihyperglycemic activity Parvathi KM, Ramesh CK, Krishna V, Paramesha M, Kuppast IJ. Antihyperglycemic activity of Anogeissus latifolia in streptozotocin induced diabetic rats. Int J Chem Sci 2009;7:1974‑82.[7] Guduchi (Tinospora cordifolia Willd.) Antidiabetic activity Khedekar SB, Ravishankar B, Prajapati PK. Anti‑diabetic activity of dried extract of Tinospora Cordifolia (Guduchi Ghana) and honey in streptozotacin induced diabetic rats. Int J Green Pharm 2015;9:S31.[8] Guggulu (Commiphora mukul Hook ex Antidiabetic effect Ramesh B, Karuna R, Saralakumari D. Ethanolic stocks.) extract of Commiphora mukul gum resin attenuates Streptozotocin induced alteration in carbohydrate and lipid metabolism in rats. Exp Clin Sci J 2013;12:556‑68.[9] Haridra (Curcuma longa Linn.) Antidiabetic effect Durga Prasad MV, Prakash LH, Harini A. Efficacy of Haridra Choorna in the management of Madhumeha (diabetes mellitus): A case study. World J Pharm Med Res 2016;2:280‑2. Haritaki (Terminalia chebula Retz.) Antidiabetic effect Kumar A, Kumar S, Chaudhary S, Kumar S, Dwivedi KN, Ram B. Encyclopedic study of Haritaki (Terminalia chebula Ritz.) in reference to prameha. J Med Sci Res 2017;05:25484‑91. Kadali (Musa sapientum) Hypoglycemic effect Dhanabal SP, Sureshkumar M, Ramanathan M, Suresh B. Hypoglycemic effect of ethanolic extract of Musa sapientum on alloxan‑induced diabetes mellitus in rats and its relation with antioxidant potential. J Herbal Pharm 2005;5:7‑19. Kakamachi (Solanum nigrum Linn.) Antihyperglycemic activity Maniyar YA, Umamageswari MS, Karthikeyan TM. Evaluation antihyperglycemic of aqueous extract of leaves of Solanum nigrum in alloxan‑induced diabetes rats. Int J Pharm Biosci 2012;2:312‑9. Arjuna (Terminalia arjuna Roxb.) Antidiabetic effect Ragavan B, Krishnakumari S. Antidiabetic effect of T. Arjuna bark extract in alloxan‑induced diabetic rats. Indian J Clin Biochem 2006;21:123‑8. Karavellam (Momordica charantia Linn.) Antidiabetic effect Joseph B, Jinni D. Antidiabetic effect Momordica charantia (Bitter melon) and its medicinal potency. Asian Pac J Trop Dis 2013;3:93‑102. Katuki (Picrorhiza kurroa Royle. Ex Benth) Antidiabetic activity Husain GM, Singh PN, Kumar V. Antidiabetic activity of standardized extract of Picrorhiza Kurroa in rat model of NIDDM. Drug Discov Ther 2009;3:88‑92.

(Contd...)

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S145 Singh, et al.: Miraculous Herbs for Prameha ( Diabetes)

Table 3: (Continued) Name of the drug Reported References pharmacological activity Khadira (Acacia catechu Willd.) Antidiabetic activity Srivastava SP, Mishra A, Bhatia V, Narender T, Srivastava AK. Acacia Catechu hard wood: Potential anti‑diabetic cum anti‑dyslipidemic. Med Chem Res 2011;20:1732‑9. Mahanimba (Melia azedarach Linn.) Antihyperglycemic effect Prashant K, Irchhiaya R, Lawrence R, Verma A, Singh K, Ahirwar V, et al. Antihyperglycemic Effect of the Leaves of Melia Azedarach on alloxan induced diabetic rats. Int J Pharm Prof Res 2014; 5:1121‑4. Mandukaparni (Centella asiatica Linn.) Antihyperglycemic activity Kabir AU, Samad MB, D’Costa NM, Akhter F, Ahmed A, Hannan JM. Anti‑hyperglycemic activity of Centella asiatica is partly mediated by carbohydrase inhibition and glucose‑fiber binding. BMC Complement Altern Med 2014;14:31. and it also relieves in burning micturition, whereas an ushna performed on many of them. Thus, there is an urgent need virya drugs increase agni and diminish the production of to conduct research on that valuable herbs. ama.

Allopathic drugs used for the treatment of diabetes have their own REFERENCES side effect and adverse effects such as hypoglycemia, nausea, vomiting, hyponatremia, flatulence, diarrhea or constipation, 1. Chaukambha Bharati Academy. Caraka Samhita, of alcohol flush, headache, weight gain, lactic acidosis, pernicious Agnivesa, Revised by Caraka and Dridhabala, Elaborated anemia, dyspepsia, dizziness, and joint pain. Hence, instead Vidyotini HindiCommentary by Pt. Kashinatha Shastri, of allopathic drugs, herbal drugs are a great choice which has Dr Gorakha Nath Chaturvedi, Vol. 02. Varanasi: minimum or no side effects and adverse effects. Chaukambha Bharati Academy; 2011. p. 227. 2. Chaukambha Bharati Academy. Caraka Samhita, of Agnivesa, Revised by Caraka and Dridhabala, Elaborated CONCLUSION Vidyotini Hindi Commentary by Pt. Kashinatha Shastri, Dr Gorakha Nath Chaturvedi. Vol. I. Varanasi: Formulations of these medicinal plants are prepared in the Chaukambha Bharati Academy; 2011. p. 633. form of Swaras (juice), Kalka (paste), Kwath (decoction), 3. Chaukhambha Bharati Academy. Dravya Guna Vigyana Churna (powder), Vati (tablet), Avaleha (lickables), by P.V. Sharma. Vol. 2. Varanasi: Chaukhambha Bharati Academy; 2011. Guggulu (tablet form), etc. and advised according to 4. Chaukambha Bharati Academy. Bhavaprakasha Nighantu severity of disease and strength of patient. The present of Bhavamishra, Commentary by Krishnachandra study aims to collect information on various medicinal Chunekar, Edited by Ganga sahaya Pandey. Varanasi: plants indicating in Prameha (diabetes). Furthermore, Chaukambha Bharati Academy; 2010. on evaluating the reported pharmacological actions of 5. Chaukambha Orientatlia: Caraka Samhita. Vol. 1. these drugs, Table 1 emphasizes on the pharmacological Translated by Prof. P. V. Sharma. Varanasi: Chaukambha properties (Guna Karma) of these Pramehahar plants along Orientatlia; 2011. p. 274. with references. Table 2 shows drugs of herbal origin and 6. Chaukambha Bharati Academy. Caraka Samhita, of their particular action (Pramehara/pramehanuta/mehajeta/ Agnivesa, Revised by Caraka and Dridhabala, elaborated mehahara) as mentioned in Bhava Prakasha Nighantu. Vidyotini Hindi Commentary by Pt. Kashinatha Table 3 shows previous research carried on Diabetes. Shastri, Dr Gorakha Nath Chaturvedi. Vol. I. Varanasi: Various research articles are studied which provides a clear Chaukambha Bharati Academy; 2011. p. 639. evidence of their Pramehahar potential. Most of herbs are available in the market, and no research work has been Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S146 Efficacy of Ayurvedic drugs in the management of gouty arthritis – A case study

Santosh Kumar Maurya1, Dinesh Kumar Verma2 1Department of Dravyaguna, Shanti Ayurvedic Medical College and Hospital, Ballia, Uttar Pradesh, India, 2Department of Rasa Shastra, Shanti Ayurvedic Medical College and Hospital, Ballia, Uttar Pradesh, India

CASE REPORT Abstract

Our day-to-day life is very much influenced by joint pain conditions in old age. However, these conditions include osteoarthritis, rheumatoid arthritis, and gouty arthritis. Gouty arthritis is characterized by hyperuricemia, deposition of uric acid crystals in and around joints, as well as nearby soft tissues. Change in lifestyle has strong impact on incidence of gouty arthritis. Modern treatment with synthetic drug neither able to subside painful conditions for longer duration nor completely cure the diseases. Ayurveda describes gouty arthritis under the name of vatarakta in its classics. Several herbal, herbomineral preparations were reported in classics which are helpful in gouty arthritis. In the present article, we report success story of Ayurvedic medicines in a complex case of a 54-year-old male with polyarticular tophaceous gouty arthritis with disabling effects in hand and feet.

Key words: Gouty Arthritis, Vatarakta, Ayurveda

INTRODUCTION therapy is one of the most faithful medical systems in Indian subcontinent, where plants are essential element of society yperuricemia as a result of altered and lifestyle. We are witnessing a golden age of scientific purine metabolism contributes and systematic development of Ayurveda in the treatment of in rheumatic disorder known as such type of chronic diseases. In the present article, we report H[1] success story of Ayurvedic medicines in a complex case gout. Long-term untreated condition leads to monoarticular arthritis, intercritical period, and of a 54-year-old male with polyarticular tophaceous gouty chronic tophaceous gout where monosodium arthritis with disabling effects in hand and feet. urate (MSU) crystals were deposited in connective tissues and kidneys.[2,3] The disease usually affects middle-aged and elderly men CASE REPORT over 40 years and postmenopausal females. Numerous risk factors, namely, genetics, age, A 54-year-old male patient was presented to our OPD at and gender or modifiable risk factors including Shanti Ayurvedic Medical College, Ballia. The patient was hyperuricemia, diet, alcohol, medications, body a farmer and belongs to near village Bairiya. He has long mass index, and physical fitness.[4] Overall, history of pain, swelling, and redness in his right great toe as well as pain, swelling, and deformity of small and large typical clinical manifestations of the disease are joints of both hands and feet without morning stiffness for swelling, pain, tenderness, heat at joints, flares, approximately 6 years. According to the patient, when he tophi, and urate arthropathy.[5] Joint stiffness, woke up at midnight, unbearable pain occurs in his toe, and mobility issues, and erythema also present in the morning, the toe was dark red and warm. Initially, in some cases. In a typical practice, urate- he took medicine from local health practitioner and treated lowering therapy is of main concern. Treatment with indomethacin leading to the relief over a period of time. includes non-steroidal anti-inflammatory drugs Subsequently, the patient developed recurring incident of (NSAIDs), colchicine, and corticosteroids. polyarthritis with painless nodules on hand and feet. Then, Intra-articular corticosteroid injection is also used in advance cases.[6] Non-pharmacological measures are also helpful in controlling the Address for correspondence: Santosh Kumar Maurya, Shanti Ayurvedic Medical progress of disease. Several alternative therapies College and Hospital, Ballia, Uttar Pradesh, India. are also used by the patients to treat acute E-mail: [email protected] painful episodes of gouty arthritis.[7] Plant-based

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S147 Maurya and Verma et al.: Ayurvedic management of gouty arthritis he goes to modern medicine doctor, and he was advised to take allopurinol for 4 months with protein restricted die as his serum uric acid levels reach up to of 11.93 mg/dL. The patient comes to us for better one. On the first visit of the patient, the following observations were made [Figure 1].

He was afebrile, cardiovascular and respiratory system parameters were normal. Locomotor system examination demonstrates muscular atrophy of limbs and multiple deformities of wrists, proximal interphalangeal joints (PIP), metacarpophalangeal joints of hands, and metatarsophalangeal joints of feet. Non-inflammatory subcutaneous nodule of variable sizes (1–2 cm) also present at joints. Biochemical investigation shows hemoglobin 13.6 g/dL, thin-layer chromatography of 7800/µL, platelet counts of 130 × 103/µL, Figure 1: Blood report before treatment ESR of 18/mm 1st h, uric acid of 13.46 mg/dL, creatinine of 1.04 mg/dL, negative rheumatoid factor, and C-reactive protein 12 mg/L. X-ray confirms the disease as joint space was reduced, subarticular cysts were present at PIP of middle finger of the left hand. Bilateral reduction of joint spaces and presence of subarticular cysts was also observed in X-ray of feet. Histopathology nodule shows the presence of tophus while no atypical cells were observed.

Drug and Treatment Protocol

The patient was advised to take the following medicine for 3 months as follows: 1. Bodhivriksha Kashaya: 50 mL twice daily 2. Vata gajankush Ras: 365 mg twice daily 3. Amrita Guggulu: 500 mg twice daily Figure 2: Blood report after treatment 4. Punarnava Guggulu: 500 mg twice daily 5. Amrutadi Taila: For local application.

Follow-up was done on every 7th day during the 1st month and later once in 15 days for next 2 months. Assessment was made on the basis of subjective and objective parameters (radiological findings) both before and after treatment. After administration of drug by the end of 3rd week of the treatment, the patient gets relief from pain. He was able to do his day-to-day life work. He was instructed to strictly follow the prescribed diet regime and lifestyle. In next 20 days, the changes appear in radiological findings. Blood report reveals that uric acid was significantly reduced. The treatment will continue till the complete removal of tophus [Figures 2 and 3].

DISCUSSION Figure 3: X-ray report after treatment

Gout is a metabolic disorder where uric acid levels exceed its lead to nephrolithiasis and renal damage.[8] These changes higher limit 6.8 mg/dL because uric acid excretion through manifest certain radiologic changes asymmetrical, erosive kidney was impaired.[2] The excess uric acid deposited in the arthritis with preserved articular surface in gouty arthritis. joint and soft tissues as needle-shaped crystal of MSU known Bone erosions may be seen in advance stage due to tophi as tophus.[5] The most common sites are skin overlying joints deposition.[9] The treatment approaches toward gouty arthritis and helix of the ears. Usually, the tophi are formed after a has been changed a lot in recent years. The pharmacological mean period of 10 years of disease duration. This may measures NSAIDs, colchicine, and steroids should not be

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S148 Maurya and Verma et al.: Ayurvedic management of gouty arthritis used for a longer period due to their side effects. Hence, the 2. Hamburger M, Baraf HS, Adamson TC 3rd, Basile J, use of Ayurvedic medicine in case of arthritis increases day- Bass L, Cole B, et al 2011 recommendations for the by-day. Medicinal plants and mineral drug from Ayurveda diagnosis and management of gout and hyperuricemia. science can be very helpful in the treatment of hyperuricemia Postgrad Med 2011;123:3-6 and gout. Ayurveda encourages incorporation of lifestyle 3. Wallace SL, Robinson H, Masi AT, Decker JL, modification along with specific herbs and minerals to cure McCarty DJ, Yu TF. Preliminary criteria for the various diseases.[7] The effects of such Ayurvedic drugs are classification of the acute arthritis of primary gout. purely based on observation. Arthritis Rheum 1977;20:895-900. 4. Saag KG, Choi H. Epidemiology, risk factors, and lifestyle modifications for gout. Arthritis Res Ther 2006;8:S2. CONCLUSION 5. Annemans L, Spaepen E, Gaskin M, Bonnemaire M, Malier V, Gilbert T, et al. Gout in the UK and Germany: Polyarticular tophaceous gouty arthritis is uncommon Prevalence, comorbidities and management in general considering pharmacological treatment of hyperuricemia practice 2000-2005. Ann Rheum Dis 2008;67:960-6. and such cases may be considered as differential diagnosis 6. Stamp LK, O’Donnell JL, Chapman PT. Emerging for rheumatoid arthritis so that early treatment will stop the therapies in the long-term management of hyperuricaemia disability effects in such patients. We have treated the patients and gout. Intern Med J 2007;37:258-66. 7. Kushwaha AK, Maurya SK. Herbal approach toward with such symptoms successfully with the Ayurvedic drugs. Vatarakta (Gout), a Metabolic Syndrome: A review. Int J Thus, the current case confirms that herbal treatment of gouty Ayu Pharm Chem 2014;2:22-43. arthritis can be achieved with the Ayurveda. 8. Ahmad SJ, Khurshid S. Polyarticular tophaceous gouty arthritis: A case report. Int J Case Reports Images 2013;4:554-8. REFERENCES 9. Schlesinger N, Thiele RG. The pathogenesis of bone erosions in gouty arthritis. Ann Rheum Dis 1. Lai SW, Liu CS, Lin T, Lin CC, Lai HC, Liao KF. 2010;69:1907-12. Prevalence of gout and hyperuricemia in Taiwan: A hospital-based, cross-sectional study. South Med J 2009;102:772-3. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S149 Prediabetes - an Ayurvedic review (review article)

Sarita Mishra Department of Prasuti Tantra, Jeevak Ayurvedic College, Chandauli, Varanasi, Uttar Pradesh, India

Abstract

In today’s fast world, people are not aware about consequences of their busy lifestyle on body. Prediabetes is a condition that is result of disturbed lifestyle and metabolism of a person and if not managed at proper time results in various disorders like increased risk for diabetes and cardiovascular disease. As per Ayurvedic concept, health is the state of proper functioning of dosha, dhatu, and mala. These factors are under the control of proper functioning

REVIEW ARTICLE REVIEW of agni and ahara consumed by particular person. By giving proper consideration to agni to maintain homeostasis of body, various metabolic disorders can be managed much earlier stage.

Key words: Agni, Ayurveda, metabolic disorders, prediabetes

INTRODUCTION and ama that will help in prevention and management of prediabetes in better way. rediabetes is the precursor stage before diabetes mellitus in which not all of the Psymptoms required to diagnose diabetes LITERATURE REVIEW are present, but blood sugar is abnormally high.[1] It is not a disease; the American Agni has been considered as route cause of body by Diabetes Association says, “prediabetes should maintaining organism’s integrity and vitality by converting not be viewed as a clinical entity in its own the food consumed in various ways into various structural right but rather as an increased risk for diabetes and functional components, i.e., dhatu and dosha. Function and cardiovascular disease. Prediabetes is of Jatharagni includes digestion of food and Saarakitta associated with obesity, dyslipidemia, high vibhajana (absorption).[3] After the function of jatharagni triglycerides, and hypertension.” It is thus a ahara rasa get form, then bhootagni and dhatvagni come metabolic syndrome, and it usually involves no into play so vijateeya ahara rasa get converted into sajateeya symptoms and only high blood sugar as the sole to different mahabhutas[4] of body and after functioning of sign. Insulin resistance, the insulin resistance dhatupaka gives nourishment to body tissue. However, when syndrome (metabolic syndrome or syndrome proper functioning of agni gets disturbed, ama get formed X), and prediabetes are closely related to one at various levels in body that leads to different pathological another and have overlapping aspects. conditions.[5]

Insulin enters cells first by binding to target When food gets properly digested, it forms sara and kitta insulin receptors. DM and some of those with bhaga. Sara bhaga gets absorb and after digestion with prediabetes have impaired glucose tolerance dhatvagni forms sthayi and asthayi poshaka dhatu. Sthayi in these individuals; blood glucose rises to poshaka dhatus gives nutrition to permanent dhatu, i.e., sthayi abnormally high levels. This may be due to a rasa Dhatu gives nutrition to rasa dhatu proper and asthayi lack of pancreatic hormone release or failure of rasa dhatu after functioning of raktagni forms sthayi and targeted tissues to respond to the insulin present asthayi rakta dhatus, in the same manner, other dhatus get or both. Obesity is thought to be a major cause form and get their nutrition from their previous dhatus.[6] of insulin resistance at tissue level.[2] Address for correspondence: Sarita Mishra, Department of Prasuti Tantra, Jeevak Objective Ayurvedic College, Chandauli, Varanasi, Uttar Pradesh, India. Phone: +91-8948888894. This work will help in better understanding of E-mail: [email protected] pathogenesis of prediabetes in relation to agni

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S150 Mishra: Prediabetes and Ayurveda

Disturbance in function of agni at any level, i.e., jatharagni, as toxins, microbes, and undigested food particle and get absorb bhutagni, and dhatuvagni leads to the formation of ama in blood stream and act like chronic stressor at cellular level that is causative factor of different pathological conditions. in whole body. Chronic stress at cellular level induces various However, gross digestion takes place in amashaya that is factors like betatrophin that alters fat metabolism. Altered fat why acharya has described the formation of ama, primarily metabolism is responsible for insulin resistance and leads to in amashaya. prediabetic stage. Ayurvedic concept of agni and Dhatu poshan can help in better understanding and management of altered gut Symptoms of Ama[7] - Srotarodha - obstruction - this can occur permeability, cellular stress, and fat metabolism. In preventive in any large, small or minute channel when it is indicated by aspect, we can aware people about food habits that help stagnation and disturbance in transport and metabolism in selection of food according to their prakriti, nature of food, and gross as well as at cellular level. Weakness or reduced working status of their agni, i.e., person having kaphaj prakriti should power in any part of body or organ is due to obstruction in avoid excess intake of guru and snigdha ahar, he/she take ahar their nutrition caused by Ama. Other symptoms of ama are that maintains his/her agni, agnimandya[13] should not be their heaviness and lethargy in body along with coated tongue, because agnimandya is the factor which leads the formation improper digestion and incomplete evacuation. of ama at amashaya and Dhatu level that acts as chronic stressor and predisposes the person for prediabetic stage. At therapeutic level, concept of storto-shodhan and agni deepan DISCUSSION can help in prediabetic stage in better way by removing cellular stress because it is already discussed that betatrophin that is As per Ayurvedic concept, obesity is disorder related to kapha induced at cellular level due to chronic stress alters fat and lipid dosha. When a person indulges in kaphaj ahar vihar,[8] his/ metabolism. If one can improve metabolism by agni deepan her agni gets vitiated at jatharagni and dhatvagni level that and storto-shodhan with the help of langhan, deepan pachan, produces ama. As ama is the first cause of almost all diseases, and storto-shodhan by panchakarma, homeostasis of body can it causes strotodushti in the form of avarodh in strotasas and be achieved because these processes improve functioning of disturbs dhatu poshan. agni and proper Dhatu formation by clearing tissue channels, i.e., strotasas.[14,15] Agni deepan and storto-shodhan can help Modern science also believes that there are tight junctions in in the management of chronic stress at cellular level that is digestive tract, expressing different levels of tightness and responsible for altered fat and lipid metabolism by clearing permeability, based on the variety of stimuli, i.e., dietary tissue channels and tissue metabolism. stimuli, hormonal and neuronal signal, and inflammatory mediator.[9] That means permeability of intestine varies time to time in response to various types of stimulation such as CONCLUSION infection, toxic, stress, and age. There are varieties of human diseases in which abnormal intestinal permeability plays major It is very surprising that researches in the field of increase part in their pathogenesis; these diseases are diabetes, Crohn’s gut permeability and altered tissue response in disease disease, autoimmune diseases, irritable bowel syndromes, pathogenesis are in very initial phase in modern medical atopic dermatitis, and ankylosing spondylosis.[10] Before science. Pathogenesis of diabetes, rheumatoid arthritis, atopic the development of proper diseases caused by abnormal gut dermatitis, and autoimmune diseases is now redefining on permeability, various types of symptoms are developed that the basis of altered gut microbiota and increases permeability are combinedly called as leaky gut syndrome. of gut, but concept of agni and ama is very basic concept of Ayurveda that covers similar but much wider area of function Once these tight junctions get broken apart, things such as than gut microbiota and increases gut permeability along with toxins, microbes, and undigested food particle can escape role of proper digestion on body homeostasis. That is why agni from intestine and reach in blood stream and acting as has been considered as cause of life and body (dehadharan) antigen and causes chronic stress at cellular level and result and ama as route cause of all disease (sarva dosha prakopana). in various metabolic and autoimmune disorders. Chronic Hence, by giving consideration to concepts related to agni, stress stimulates production of betatrophin, a protein that then Dhatu poshana, strotovarodh, and ama in researches related goes on to inhibit an enzyme involved in fat metabolism.[11] to intestinal permeability and insulin resistance, management Betatrophin reduces the body’s ability to break down fat and of prediabetes can be done in better way. Thus, concept of slows down fat metabolism. Increase body fat is the major agni and ama can give new vision in the field of maintenance cause of insulin resistance and thus for prediabetes also.[12] of health and cure of disease.

Proper function of agni is responsible for the maintenance of local environment of gut and formation of dhatu and if it get REFERENCES disturbed, it causes the formation of ama at each level of body that is the condition which is similar to the condition when tight 1. Hanefeld M, Koehler C, Fuecker K, Henkel E, junctions of gut get weaken in response to various factors such Schaper F, Temelkova-Kurktschiev T; Impaired Glucose

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Tolerance for Atherosclerosis and Diabetes study. (Mar Sutra Sthan, Dwividhoupkramniya Adhyay (14/18-20). 2003). Insulin Secretion and Insulin Sensitivity Pattern Varanasi: Chaukhambha Sanskrit Pratishthan; 2011.p.194. Is Different in Isolated Impaired Glucose Tolerance and 9. Hossain Z, Hirata T. Molecular mechanism of intestinal Impaired Fasting Glucose. Diabetes Care Mar 2003; permeability: Interaction at tight junction. Mol Biosyst 26:868-84. 2008;4:1181-5. 2. Understanding Prediabetes, National Diabetes Service 10. Ulluwishewa D, Anderson RC, McNabb WC, Scheme Pre-Diabetes Fact Sheet. Diabetes Astralia. Moughan PJ, Wells JM, Roy NC, et al. Regulation of 2016. tight junction permeability by intestinal bacteria and 3. Chaukhambha Sanskrit Pratishthan. Vagbhatt, Ashatanga dietary components. J Nutr 2011;141:769-76. Hridyam, Nirmala Hindi Vyakhyaa, Tripathi Brahmanand, 11. Odenwald MA, Turner JR. Intestinal permeability Sharirsthan, Angavibhag Sharir Adhyay (3/64). Varanasi: defects: Is it time to treat? Clin Gastroenterol Hepatol Chaukhambha Sanskrit Pratishthan; 2011. p. 378. 2013;11:1075-83. 4. Choukhabha Bharati Academy. Agnivesh, Charaka Samhita, 12. Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Vidyotini Hindi Vyakhyaa, Shashtri Kashinath, Chaturvedi Schulzke JD, Serino M, et al. Intestinal permeability – Gorakhanath Grahani Dosha Chikitsa (15/13,14). Varanasi: a new target for disease prevention and therapy. BMC Choukhabha Bharati Academy; 2006. p. 454. Gastroenterol 2014;14:189. 5. Choukhabha Bharati Academy. Charaka Samhita, 13. Zhu JZ, Yu CH, Li YM. Betatrophine, Diabetes and Lipid Vidyotini Hindi Vyakhyaa, Shashtri Kashinath, Chaturvedi Metabolism, Biomedical Report 2: 2015. p. 447-451. Gorakhanath Grahani Dosha Chikitsa (15/44). Varanasi: 14. Chaukhambha Sanskrit Pratishthan. Vagbhatt, Choukhabha Bharati Academy; 2006. p. 460 Ashatanga Hridyam, Nirmala Hindi Vyakhyaa, Tripathi 6. Choukhabha Bharati Academy. Charaka Samhita, Brahmanand, Sutra Sthan, Dwividhoupkramniya Vidyotini Hindi Vyakhyaa, Shashtri Kashinath, Chaturvedi Adhyay (12-14). Varanasi: Chaukhambha Sanskrit Gorakhanath Grahani Dosha Sutra Sthana (28/4). Varanasi: Pratishthan; 2011. p. 192. Choukhabha Bharati Academy; 2006. p. 569. 15. Chaukhambha Sanskrit Pratishthan. Vagbhatt, Ashatanga 7. Chaukhambha Sanskrit Pratishthan. Vagbhatt, Hridyam, nirmala Hindi Vyakhyaa, Tripathi Brahmanand, Ashatanga Hridyam, Nirmala Hindi Vyakhyaa, Sutra Sthan, Doshoupkramniya Adhyay (13/28,29). Tripathi Brahmanand, Sutra Sthan, Doshoupkramniya Varanasi: Chaukhambha Sanskrit Pratishthan; 2011. Adhyay (13/23,24). Varanasi: Chaukhambha Sanskrit p. 188. Pratishthan; 2011. p. 188. 8. Chaukhambha Sanskrit Pratishthan. Vagbhatt, Ashatanga Hridyam, Nirmala Hindi Vyakhyaa, Tripathi Brahmanand, Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S152 Conceptual study of Langhana karma W.S.R. to Gurvadi Guna

Shrikant Pandey, B. K. Dwibedy Department of Siddhant Darshan, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

When we think about cause, prevention, and cure of any disease, we think about various possible factors. Langhana karma is one of among them. It is the causative and contraindicated factors for some pathological conditions like gulma, especially vataja. It may be used as a preventive measure for some pathological condition

REVIEW ARTICLE REVIEW like amadosha and it is often used as treatment procedure in various diseases such as Chardi and Atisara. Various literature reviews revealed that Langhana karma is one of the two main pillars of Ayurveda regarding Chikitsa karma - Aptarpana and Santarpana. Inside the body, all the components have their own properties in form of Gurvadi Guna. Outside the body, in this world, various ahara, vihara, and ausadha, etc., also have Gurvadi guna which are responsible for their functions. Therefore, in this article, it is tried to explore the various aspects of Langhana karma and its importance in chikitsasastra with the help of knowledge of Gurvadi guna.

Key words: Aptarpana karma, Gurvadi guna, Langhana karma, Santarpana karma

INTRODUCTION reduces the body weight and causes lightness in the body is called Langhana (reducing therapy). Langhana karma is yurveda has aim to achieve the “Sama” described as a weight reducing, dhatus reducing, vata promoting/ status or balance status of Doshas, aggravating, kapha diminishing, agni promoting, ama digesting, ADhatus, and Malas, etc. If Doshas and ama preventing procedure in different texts of Ayurveda. increased or decreased, there is an abnormal This procedure is described both as one of the causative factor status known as Vikara or disease. Hence, the of many diseases as well as curative procedure of many diseases. main aim of Ayurveda is to increase and decrease Dosha, Dhatu, and Mala, etc. The principles of Gurvaadigunas are the specific contribution of Ayurveda, remedies are described from the different point i.e., it is not described in any other darshana or text, as of view, i.e. Shodhan and Samshamana. The described in Ayurveda. The concept of Guna is described in five special procedure known as Panchkarma Ayurveda from applied and therapeutic view. These are the is recommended as Shodhana therapy while group of 10 pairs of gunas. These gurvadi gunas perform subsiding the aggravated Doshas are known as specific karmas while residing in the dravyas. These karmas Shamana therapy. These types of remedy are are the basis of treatment and cause of diseases. Langhana applied to manage the disease, but in Charaka karma is performed through specific ahaar, vihara, and Samhita, in context of the “basic principles of ausadh. And all these ahara have specific type of gurvadi remedy,” in the title of लङ्घनंहृ णीयोऽध्याय gunas responsible for Langhana karma. Six types of special remedies are described:

1. Langhana 2. Bringhana AIMS AND OBJECTIVES 3. Rukshana 4. Snehana The aim of this study is to collect, compile, and explore the 5. Svedana applied aspect of Langhana karma for healthy and diseased 6. Stambhana.[1] Address for correspondence: There is no any other remedy in Ayurveda which Shrikant Pandey, Department of Siddhant Darshan, might be beyond of these remedies. All the Faculty of Ayurveda, Institute of Medical Sciences, remedies described in Ayurveda may be included Banaras Hindu University, Varanasi, Uttar Pradesh, India. under this. Among these, the Upkrama which E-mail: [email protected]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S153 Pandey and Dwibedy: Langhana karma and Gurvadi Guna patient from various corners of Ayurvedasastra, so that the contentment. These are the signs and symptoms of proper vast knowledge of Langhana karma may become concised in administration of Langhana therapy.[6] the light of Gurvadi guna and every concept could be studied under this. Lakshana of Atilanghana

Parvabheda, Angamarda, Kasa, Mukhasosha, Loss of LITERATURE REVIEW appetite, Aruchi, Trishna, weakness of ears and eyes, loss of memory, upward movement of Vata, emaciation of body, loss Ayurvedic literature related with Langhana were studied and of the power of digestion, and strength are the lakshana of interpreted to explore the concept of Langhana, its mode of atilanghana.[7] action as causative as well as a curative measure for various diseases in the light of gurvadi guna. For understanding the concept of Langhana karma, Ayurvedic literatures, related Langhana Karma as Nidana of Various Diseases with Gurvadi Guna and gurvaadiguna were also studied. 1. Raaj Yakshama: Vayu gets aggravated due to injury to the chest caused by fighting, reading loudly, carrying CONCEPT OF LANGHANA KARMA excessive weight, walking long distance, observing fast for a long time, etc., are the etiological factors of The procedure or process which reduces the body weight or tuberculosis caused by overexertion.[8] reduce the diameter of body or degenerates the body cells is 2. Vaat Arsha: Fasting, residing in cold country and cold known as Langhana.[1] season, and physical exercise are the etiological factor of Vaatika type of piles.[9] 3. Vata Vyadhi: Keeping fast in excess, etc., are the [10] TYPES OF LANGHANA KARMA causative factors for the generation of Vata Vyadhi. 4. Karsyata: Excessive emaciation is caused by the intake The four types of elimination therapy, control of thirst, of ununctuous diets, drinks, fasting, intake of food in exposure to wind and sun, intake of substance that stimulate inadequate quantity, overadministration of elimination digestion, fasting, and physical exercise constitute reducing therapies, and grief suppression of natural urges [11] therapy.[2] The Langhana therapy is of two types - Sodhana including the urge for sleep. and Shamana.[3] 5. AshmariRoga: Running, fasting, swimming, etc., aggravates the pain in the patients of Ashmari.[12]

Properties of Langhana Dravya Langhana Karma as Treatment Measure in Commonly, this process is performed through Laghu guna, Following Disease but there are some other Gunas which supports the process in Charaka Samhita in reference of Langhana karma. Laghu 1. Jwara: The Doshas residing in the Amasaya, destroy the guna has been enumerated first, but other Gunas are also fire, become Sama, obstruct the passages, and produce mentioned which have an important role in Langhana karma, fever, therefore, Langhana should be done.[13] i.e., Ushna, Tikshna, Vishada, Ruksha, Sukshma, Khara, 2. Gulma: In the case of Kaphaja Shula, Vamana, Sara, and Kathina (hard).[4] Langhana, Mardana, Swedana, KshapanaKarma should be done. Snehana, etc., karmas should be done in all type of Gulma on the basis of Dosha and condition.[14] Persons Advised for Langhana Karma 3. Avipakaja shula: In the case of Avipakaja shula, Vamana, Langhana, Swedana, Pachana, Phalavarti, Khsara, Reducing therapy is to be administered in winter to such of Churna, and Gutika are used.[15] the patient as are suffering from skin disease and obstinate 4. Chardi Vega Dharana Janya Vyadhi: Induction of urinary disorder and to those who possess corpulent body vomiting, smoking, fasting, etc., are indicated in diseases together with unctuousness and fluidity and even to those caused by suppression of urge of vomiting.[16] who suffer from diseases due to vitiation of Vata.[5] 5. RaktajaVikara: Langhana is the one of the treatment measures in the vitiation of Rakta.[17] Lakshana of Samyag Langhana 6. Amasayottha Vikara and Jwara: Diseases having their origin from Aamasya are cured by fasting. Fasting is a Proper excretion of flatus urine and feces, lightness of body, therapy for the cure of fever alone.[18] feeling of purity in heart, eructation, throat and mouth, 7. Visuchika: During treatment of Visuchika Langhana disappearance of drowsiness and exertion, appearance of should be given firstly followed by management given sweat and taste for food, excessive hunger and thirst, and after Virechana.[19] In the case of curable Visuchika,

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Dahana karma should be done on both Parshini along therapies. However, bleeding should not be stopped with this, Teekshna Vamana, Agni-Seka should be done immediately and one should wait for appropriate time or in Amavastha. If Doshas are about to Pakwa condition, the patient can be given fasting therapy.[35] then Langhana Karma and Swedana Karma should be 16. Raktarsha: When the blood is vitiated, Sodhana and also done for Pachana and also Virechana Karma should be Langhana should be done depending on the strength of done.[20] person.[36] 8. As a type of AptarpanaVidhi: Aptarpana is of three types 17. Ama (Grahani): If the Dosha as are in its Ama stage and - Langhana, Langhana Pachana, and Dosavsechana.[21] pervades other parts of the body, then the patient should 9. Sleshma Prakopa: Running, fasting, swimming, whirling, be made to fast and be given drugs condusive to Pachana sleeping, awake during night, fighting, sexual intercourse, of the undigested material, e.g., Yavagu.[37] In condition exercise, unction, bath, and oil massage are some of the of Ama, Langhana should be done. In condition of measures in the management of Slesma Prakopa.[22] Vidagdhata, emesis should be done. In Vistabdhata, 10. Jwara: In the first stage of Jwara fasting is described. fomentation should be done and in Rasshesajeerna sleep It is however not indicated in the Jwara caused by should be advised.[38] consumption, aggravation of Vayu, fear, anger, passion, 18. Atisara: If the Doshas are only slightly aggravated and grief, and physical exertion.[23] Fasting, fomentation, causing diorrhea, then fasting therapy is very useful.[39] time or passage of 8 days, medicated gruels, and drugs In the case of Slesmatisar, Langhana, and Pachana, having bitter in taste. These help in Pachana of Avipkva therapy should be prescribed initially.[40] For the treatment Doshas in the first stage of fever.[24] Langhana therapy of Atisara, Langhana should be done initially, and then, and similar other therapy described in the 22 chapter Yavagu, made of Pachana drugs, should be given.[41] of Sutra Sthana should be invariably administered 19. Chardi: Since all the varieties of Chardi are caused by in following condition - first, when the Jwara in the agitation of Doshas in the stomach, Langhana therapy Sama state. Second, when Khapha is aggravated to should be administered for their cure. These fasting produce the Jwara. Third, when both the Kapha and therapy should not be administered to a patient suffering Pitta are aggravated together.[25] The Doshas residing in from Vatika type of Chardi.[42] In general, vomiting arises the Amasaya, destroy the fire, become Sama, obstruct from the upward movement of the Doshas localized in the passages, and produce fever, therefore, Langhana the Amasaya, hence for them, Langhana is ideal in the should be done.[26] In patients of Jwara having unstable beginning itself except in that caused by Vata.[43] Dosha and Agni, Langhana should be done to digest 20. Pratisyaya: Pratishyaya associated with Vamana, AamaDosha. Langhana destroyes the Jwara, stimulates Angasada, Jwara, Gaurava, Aruchi, Arti, and Atisara, the Agni, and increase the interest in food and makes the etc., should be treated by Langhana initially and then by body light.[27] Deepana and Pachana.[44] 11. Vishama Jwara: When Kapha is predominant then for 21. Avarana Vata Chikitsa: When the Vata is Sama, it the patient emetic therapy, Pachana, ununctuous diet should be made Nirama by treatments such as Svedana, and drinks, fasting, and hot decoction are useful.[28] On Langhana, Pachana, application of pastes, and pouring the day of onset of fever, either Langhana or Bringhana medicinal liquids which are dry, and then, the treatments should be adapted first.[29] suitable for Vata alone should be given.[45] 12. Raktapitta: Keeping in view the tracks through which the diseases is manifested, the association of Doshas and the causative factors, a physician should administer CONCEPT OF GURVADI GUNA either Langhana or Tarpana therapy in the beginning of Raktapitta.[30] On the basis of the condition of Desha These are also known as Sharir gunas as they are found in and Kala, treatment of Raktapitta should be commenced the body tissues and substances influencing them. While either with Langhana or Bringhana with either Sodhana describing Samanya gunas, description of these Gurvadi Gunas or Shamana.[31] along with Paradi gunas is given by Acharya Chakrapani. 13. Sotha: If Svayathu is caused by Ama, then the patient Both these groups of Gunas Gurvadi and Paradi are present should be given fasting therapy, Pachana and Shodhana, in Panchmahabhutas, i.e., Prithvi, Jala, Vayu, etc. Hence, i.e., elimination therapy to alleviate the predominant these Gunas are important part in treatment part of view also Dosha involved in the pathogenesis of this disease.[32] For while application of Samanya-vishesha Siddhant, etc.[46] There their treatment, Siravyadha, Kayavireka, and Dhooma, are twenty Gurvadi guna appearing in ten pairs and each pair intake of old ghee, and fasting should be administered.[33] having opposite characteristics.[47] Charaka, Sushruta, and 14. Jaalagardabha: Fasting, bloodletting, therapy causing Vagbhatta has mentioned the same number of Gurvaadi Gunas, dryness, purificatory therapies, recepies of Dhatri, but there are some differences in type of Gunas considered by and cold application of body should be done always in these Acharyas which is given in following Table 1. Jalagardabha.[34] 15. Pittaslesmic Arsha: If there is predominance of Pitta and Comparison between two Gunas in each pair relatively explains Kapha, the patient should be administered elimination the counteraction and usefulness as per the requirement.

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Table 1: Types of Gurvadi Gunas described in different Samhitas Pair of Gunas Charaka Samhita Sushruta Samhita Astanga Hridaya/Sangraha Rasa‑Vaisesika Guru‑Laghu Considered Considered Considered Considered Sheeta‑Ushna Considered Considered Considered Considered Snigdha‑Rukshna Considered Considered Considered Considered Manda‑Tikshna Considered × Considered × Sthira‑Sara Considered × Considered × Mridu‑Kathina Considered × Considered × Vishada‑Picchila Considered Considered Considered Considered Slakshna‑Khara Considered × Considered × Stula‑Sukshma Considered × Considered × Sandra‑Drava Considered Considered Considered × Mridu‑Tikshna × Considered × Considered Sugandha‑Durgandha × Considered × × Sara‑Manda × Considered × × Ashu‑Sukshma × Considered × × Slakshna‑Khara × Considered × ×

FUNCTIONS OF GUNAS MENTIONED IN Saptadhatu, each Guna for each Dhatu. The theory of Guna LANGHANA KARMA is the basis (especially Gurvaadi Guna) of clinical evaluation of Dosha, Dhatu, and Mala as, for example, Kapha has Guru 1. Ushna guna: It is opposite to sheeta guna, and especially guna while Vata has Laghu. Vata has Sheeta guna while Pitta helps in digestion.[48] has Ushna. The relative Gunas such as Guru-Laghu and 2. Ruksha guna: It is opposite to snigdha guna, and especially Sheeta-Ushna are sheltered in different three Doshas and helps in stambhanakarma and generates kharata.[49] have a role to antagonizing activity to maintain the normal status. These Gunas are also responsible to produce the 3. Vishada guna: It is opposite to picchila guna and causes disease, while the virtue of these Guna any Dosha becomes kledana, aachushana, and ropanakarma.[50] aggravated. In other word, it can be said that Doshas takes 4. Teekshana guna: It causes daha, paka, and aggravation through Gunas. The “Anshansha Kalpana” sravanakarma.[51] (clinical gradation) is based on these Gunas. Any Dosha can 5. Laghu guna: It is opposite to guru guna and causes aggravate with one Guna, two Gunas, or more. The gradation langhana, lekhana, and ropanakarma.[52] of aggravated Dosha depends on the increase or decrease 6. Sara guna: It is responsible for anulomana karma.[53] state of Guna. 7. Sukshama guna: It is responsible for entry in the very minute spaces or pores in body.[54] “Sadopkrama” has the meaning of six procedures of 8. Khara guna: It is responsible for lekhana karma. treatment. Langhana is one of them. These six are based on 9. Kathina guna: It provides strength. Gunas. Over fulfillments or oversaturation results the disease and those diseases are known as “SantarpanaJanyaRoga.” Unsaturated states of Dhatus also produce different types of DISCUSSION diseases, which are known as AptarpanaJanyaRoga. Hence, only two ends are planned in Ayurveda “to increase” or 20 types of Gurvadi Gunas are described in Charaka Samhita “to decrease” which is known as Langhana-Bringhana or (sharir sthana 1), Susruta Samhita (sutra sthana 46), Santarpana-Apatarpana. Among six procedures, some have Astanga Hridaya (sutra sthana 1) and some other Samhitas Langhana effect and some have Bringhana effect. In these of Ayurveda only. These are not described in Darshanas or six procedures, first of all the Langhana and bringhana have anywhere else. These Gunas are considered and applied and been listed and to support these, remaining four procedures searched out only in Ayurveda. These Gunas are described are described. For Langhana Karma, Rukshana, and Svedana with relatives as Guru-Laghu, Sheeta-Ushan, etc. While are supporting procedure. Langhana is the first Upakrama other Gunas of three groups are not described in such manner described among Sadopkrama. The various meanings of because these Gurvaadi Gunas are the backbone of the Langhana are mentioned from literature point of view, but Ayurvedic therapeutic procedure. The Tridosha theory is the from medical point of view, Langhana term is applied in clinical basis, a specific classification of GurvaadiGunas. meaning of lightness of body. It is responsible for decreasing These 7 Gunas of Vata, pitta, and kapha are related with the Dhatu, Amadosha, Mala, etc. The procedure which reduces

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S156 Pandey and Dwibedy: Langhana karma and Gurvadi Guna the body weight, body shape, and SharirDhatu is known as respectively. Langhana. Commonly, the Langhana word is applied for 5. The patient visits in hospital in two conditions: first in fasting. This procedure is applied as elimination therapy or entitled diseases such as Jwara and Kamala and second to minimize the Dosha, Dhatu, and Mala, etc. In reference of in abnormal state of Dosha, Dhatu, and Mala. Langhana therapy, some Gunas have been enumerated which 6. The Langhana karma may be applied as a perfect therapy support this procedure or the Dravya which have enumerated for increased and Sama state of Dosha, Dhatu, and Mala these Gunas, performs this procedure through the Gunas, and supporting/prime therapy for the diseased condition. i.e., Laghu, Ushna, Tikshna, Vishada, Ruksha, Sukshma, 7. This work is totally conceptual. In this study, the Khara, Sara, and Kathina. Among 20 GurvaadiGunas, these concept of Gunas related with Langhana karma has 9 Gunas are mentioned in Langhana Karma. Out of these been discussed, and this procedure requires further Gunas, Laghu, and Ruksha Guna are directly responsible and development from the clinical point of view with clinical abundantly used in effect of Langhana karma. This procedure assessment. can be followed or proceed in different way which have been mentioned as four types of Sodhanachikitsa, Vamana, REFERENCES Virechna, Vasti, and Nasya, minimizing the fluid/liquid intake, exposure to wind, exposure to sun/heat, application and use 1. Agnivesha. Charaka Samhita, Hindi Commentary, of Dravyas which accelerates the digestive process, fasting, Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K. and physical exercise, etc. These processes can be applied for Sutrasthana, Langhanabringhaniyam-Adhyaya (22; 9). a selective stage. This Langhana has been also indicated in Varanasi: Chaukhambha Krishnadas Academy; 2013. two ways as Shodhana and Shamana. The good selection of p. 415. patient is must for this process as in case of skin diseases, 2. Agnivesha. Charaka Samhita, Hindi Commentary, especially in patient of overweight or in case of fat, etc. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K. Sutrasthana, Langhanabringhaniyam-Adhyaya (22; 18) Some cases are contraindicated for this process such as Vataja Varanasi: Chaukhambha Krishnadas Academy; 2013. Gulma. This Langhana mainly effects on Ama, Atisnigdha, p. 416. and Abhisyandi condition, but its clinical scope is very large. 3. Vagbhatta. Astangahridayam, Nirmala Hindi It has been considered as the best procedure for prime disease Commentary, Tripathi Bramhanand, Sutrsthana, Jwara along with the diseases produced by sustained Chardi, Dwividhopkramadiyam-Adhyayam (14;4). New Delhi: Raktavikara, Viscuchika, SlesmaPrakopa, etc. This process Chaukhamba Sanskrit Pratisthan; 2015. p. 191. is a chief process of AptarpanaChikitsa. If this process 4. Agnivesha. Charaka Samhita, Hindi Commentary, is continued for long time in normal state or not needed Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, state, various abnormalities and diseases may occur such Sutrasthana, Langhanabringhaniyam-Adhyaya (22; 12). as Raajyakshama (means loss of immunity), Vatajaarsha, Varanasi: Chaukhambha Krishnadas Academy; 2013. especially Karshyaroga, pain in Ashmari. This process is a p. 415. specific treatment of Stulata/Sthaulya. The particular process 5. Agnivesha. Charaka Samhita, Hindi Commentary, of this procedure is applied for the proper state as for fasting Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, is the proper process in Jwara and other Amavastha, the Sutrasthana, Langhanabringhaniyam-Adhyaya (22; 24). Vyayama is suitable process for a Sthaulyata or obesity, etc. Varanasi: Chaukhambha Krishnadas Academy; 2013. Clinically, this process may be applied in daily practice. p. 417. 6. Agnivesha. Charaka Samhita, Hindi Commentary, Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, CONCLUSION Sutrasthana, Langhanabringhaniyam-Adhyaya (22; 34-35). Varanasi: Chaukhambha Krishnadas Academy; 1. Gurvaadi Gunas (20 in number) are the specific 2013. p. 418. contribution of Ayurveda and the theory of Gurvaadi 7. Agnivesha. Charaka Samhita, Hindi Commentary, Guna has been developed from the clinical point of view. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, 2. The entire clinical principles are established keeping Sutrasthana, Langhanabringhaniyam-Adhyaya (22; the view of importance of Guna. The chief principle of 36-37) Varanasi: Chaukhambha Krishnadas Academy; Tridosha theory is totally based on Gurvaadi Guna. The 2013. p. 419. basis of drug application is Gurvaadi Guna. 8. Agnivesha. Charaka Samhita, Hindi Commentary, 3. The Langhana karma along with other Upakramas of Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Sadopkrama theory is based on GurvaadiGuna directly, Chikitsasthana, Rajyakshmachikitsatama-Adhyaya (8; and this LanghanaUpakrama has been established to 14). Varanasi: Chaukhambha Krishnadas Academy; maintain the DhatuSamya. 2013. p. 313. 4. The Dosha, Dhatu, and Mala have characteristics to 9. Agnivesha. Charaka Samhita, Hindi Commentary, gain the state of Vriddhi and Kshaya and Langhana and Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Bringhana are applied in case of Vriddhi and Kshaya, Chikitsasthana, Arshachikitsatam-Adhyaya (14; 13).

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Varanasi: Chaukhambha Krishnadas Academy; 2013. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, p. 474. Vimanasthana, Roganeekamvimana-Adhyaya (6; 18). 10. Agnivesha. Charaka Samhita, Hindi Commentary, Varanasi: Chaukhambha Krishnadas Academy; 2013. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, p. 848. Chikitsasthana, Vatavyadhichikitsatam-Adhyaya (28; 23. Agnivesha. Charaka Samhita, Hindi Commentary, 16). Varanasi: Chaukhambha Krishnadas Academy; Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, 2013. p. 913. Chikitsasthana, Jwarachikitsatam-Adhyaya (3; 139). 11. Agnivesha. Charaka Samhita, Hindi Commentary, Varanasi: Chaukhambha Krishnadas Academy; 2013. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, p. 127. Sutrasthana, Astaunindatiyam-Adhyaya (21; 11). 24. Agnivesha. Charaka Samhita, Hindi Commentary, Varanasi: Chaukhambha Krishnadas Academy; 2013. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, p. 403. Chikitsasthana, Jwarachikitsatam-Adhyaya (3; 142). 12. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika Varanasi: Chaukhambha Krishnadas Academy; 2013. Hindi Commentary, Shastri Ambikadutta, Nidanasthana, p. 128. Ashmarinamnidana (3; 7). Varanasi: Chaukhambha 25. Agnivesha. Charaka Samhita, Hindi Commentary, Sanskrit Sansthan; 2014. p. 311. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, 13. Vagbhatta. Astangahridayam, English commentary, Chikitsasthana, Jwarachikitsatam-Adhyaya (3; 283). Murthy K.R. Srikantha, Chikitsasthana, (1;1) Varanasi: Varanasi: Chaukhambha Krishnadas Academy; 2013. Chaukhamba Krishnadas Academy; 2009. p. 173. p. 180. 14. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika 26. Vagbhatta. Astangahridayam, English commentary, Hindi Commentary, Shastri Ambikadutta, Uttaratantra, Murthy K.R. Srikantha, Chikitsasthana, (1;1). Varanasi: Gulmapratisedham-Adhyaya (42; 75). Varanasi: Chaukhambha Krishnadas Academy; 2009. p. 173. Chaukhambha Sanskrit Sansthan; 2014. p. 345. 27. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika 15. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika Hindi Commentary, Shastri Ambikadutta, Uttaratantra, Hindi Commentary, Shastri Ambikadutta, Uttaratantra, Jwarapratisedham-Adhyaya (39; 103-104). Varanasi: Gulmapratisedham-Adhyaya (42; 145). Varanasi: Chaukhambha Sanskrit Sansthan; 2014. p. 240. Chaukhambha Sanskrit Sansthan; 2014. p. 355. 28. Agnivesha. Charaka Samhita, Hindi Commentary, 16. Agnivesha. Charaka Samhita, Hindi Commentary, Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Chikitsasthana, Jwarachikitsatam-Adhyaya (3; 295) Sutrasthana, Navegandharniyam-Adhyaya (7; 15). Varanasi: Chaukhambha Krishnadas Academy; 2013. Varanasi: Chaukhambha Krishnadas Academy; 2013. p. 188. p. 177. 29. Vagbhatta. Astangahridayam, English Commentary, 17. Agnivesha. Charaka Samhita, Hindi Commentary, Murthy K.R. Srikantha, Chikitsasthana, (1;155). Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Varanasi: Chaukhambha Krishnadas Academy; 2009. Sutrasthana, Vividhashitpeetiyam-Adhyaya (28; 25). p. 201. Varanasi: Chaukhambha Krishnadas Academy; 2013. 30. Agnivesha. Charaka Samhita, Hindi Commentary, p. 600. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, 18. Agnivesha. Charaka Samhita, Hindi Commentary, Chikitsasthana, Raktapittachikitsatam-Adhyaya (4; 30). Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Varanasi: Chaukhambha Krishnadas Academy; 2013. Nidanasthana, Apasmarnidanam-Adhyaya (8; 31). p. 205. Varanasi: Chaukhambha Krishnadas Academy; 2013. 31. Vagbhatta. Astangahridayam, English Commentary, p. 754. Murthy K.R. Srikantha, Chikitsasthana, (2;4). Varanasi: 19. Agnivesha. Charaka Samhita, Hindi Commentary, Chaukhambha Krishnadas Academy; 2009. p. 206. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, 32. Agnivesha. Charaka Samhita, Hindi Commentary, Vimanasthana, Trividhkuksheeyamvimana-Adhyaya Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, (2; 13). Varanasi: Chaukhambha Krishnadas Academy; Chikitsasthana, Swayathuchikitsatam-Adhyaya (12; 17). 2013. p. 789. Varanasi: Chaukhambha Krishnadas Academy; 2013. 20. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika p. 410. Hindi Commentary, Shastri Ambikadutta, Uttaratantra, 33. Agnivesha. Charaka Samhita, Hindi Commentary, Visuchikapratisedham-Adhyaya (56; 12). Varanasi: Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Chaukhambha Sanskrit Sansthan; 2014. p. 529. Chikitsasthana, Swayathuchikitsatam-Adhyaya (12; 80). 21. Agnivesha. Charaka Samhita, Hindi Commentary, Varanasi: Chaukhambha Krishnadas Academy; 2013. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, p. 425. Vimanasthana, Janpadodhwanshaneeyamvimana- 34. Agnivesha. Charaka Samhita, Hindi Commentary, Adhyaya (3; 43). Varanasi: Chaukhambha Krishnadas Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Academy; 2013. p. 813. Chikitsasthana, Swayathuchikitsatam-Adhyaya (12; 22. Agnivesha. Charaka Samhita, Hindi Commentary, 100). Varanasi: Chaukhambha Krishnadas Academy;

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2013. p. 431. Chaukhambha Sanskrit Sansthan; 2014. p. 156. 35. Agnivesha. Charaka Samhita, Hindi Commentary, 45. Vagbhatta. Astangahridayam, English Commentary, Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Murthy K.R. Srikantha, Chikitsasthana. (22;50). Chikitsasthana, Arshachikitsatam-Adhyaya (14; 176). Varanasi: Chaukhambha Krishnadas Academy; 2009. Varanasi: Chaukhambha Krishnadas Academy; 2013. p. 521. p. 497. 46. Agnivesha. Charaka Samhita, Hindi Commentary, 36. Vagbhatta. Astangahridayam, English Commentary, Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Murthy K.R. Srikantha, Chikitsasthana, (8;98). Varanasi: Sutrasthana, Deerghamjeevatiyam-Adhyaya (1; 44). Chaukhambha Krishnadas Academy; 2009. p. 321. Varanasi: Chaukhambha Krishnadas Academy; 2013. 37. Agnivesha. Charaka Samhita, Hindi Commentary, p. 24. Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, 47. Vagbhatta. Astangahridayam, Nirmala Hindi Chikitsasthana, Grahanidoshachikitsatam-Adhyaya (15; Commentary, Tripathi Bramhanand, Sutrsthana, 75). Varanasi: Chaukhambha Krishnadas Academy; Ayushkamiyam-Adhyayam (1; 18). New Delhi: 2013. p. 532. Chaukhamba Sanskrit Pratisthan; 2015. p. 15. 38. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika 48. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika Hindi Commentary, Shastri Ambikadutta, Sutrasthana, Hindi Commentary, Shastri Ambikadutta, Sutrasthana, Annapanavidhi-Adhyaya (46; 512). Varanasi: Annapanavidhi-Adhyaya (46; 522). Varanasi: Chaukhambha Sanskrit Sansthan; 2014. p. 288. Chaukhambha Sanskrit Sansthan; 2014. p. 289. 39. Agnivesha. Charaka Samhita, Hindi Commentary, 49. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Hindi Commentary, Shastri Ambikadutta, Sutrasthana, Chikitsasthana, Atisarachikitsatam-Adhyaya (19; 19). Annapanavidhi-Adhyaya (46; 523). Varanasi: Varanasi: Chaukhambha Krishnadas Academy; 2013. Chaukhambha Sanskrit Sansthan; 2014. p. 289. p. 655. 50. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika 40. Agnivesha. Charaka Samhita, Hindi Commentary, Hindi Commentary, Shastri Ambikadutta, Sutrasthana, Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Annapanavidhi-Adhyaya (46; 524). Varanasi: Chikitsasthana, Atisarachikitsatam-Adhyaya (19; 102) Chaukhambha Sanskrit Sansthan; 2014. p. 289. Varanasi: Chaukhambha Krishnadas Academy; 2013. 51. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika p. 669. Hindi Commentary, Shastri Ambikadutta, Sutrasthana, 41. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika Annapanavidhi-Adhyaya (46; 525). Varanasi: Hindi Commentary, Shastri Ambikadutta, Uttaratantra, Chaukhambha Sanskrit Sansthan; 2014. p. 289. Atisarapratisedham-Adhyaya (40; 25). Varanasi: 52. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika Chaukhambha Sanskrit Sansthan; 2014. p. 281. Hindi Commentary, Shastri Ambikadutta, Sutrasthana, 42. Agnivesha. Charaka Samhita, Hindi Commentary, Annapanavidhi-adhyaya (46; 526). Varanasi: Dwivedi Laxmidhar Dwivedi B.K. and Goswami P.K, Chaukhambha Sanskrit Sansthan; 2014. p. 289. Chikitsasthana, Chardichikitsatam-Adhyaya (20; 20). 53. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika Varanasi: Chaukhambha Krishnadas Academy; 2013. Hindi Commentary, Shastri Ambikadutta, Sutrasthana, p. 679. Annapanavidhi-Adhyaya (46; 529). Varanasi: 43. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika Chaukhambha Sanskrit Sansthan; 2014. p. 289. Hindi Commentary, Shastri Ambikadutta, Uttaratantra, 54. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika Chardipratisedham-Adhyaya. (49; 15). Varanasi: Hindi Commentary, Shastri Ambikadutta, Sutrasthana, Chaukhambha Sanskrit Sansthan; 2014. p. 460. Annapanavidhi-adhyaya (46; 531). Varanasi: 44. Sushruta. Sushruta Samhita, Ayurveda Tattva Sandipika Chaukhambha Sanskrit Sansthan; 2014. p. 289. Hindi Commentary, Shastri Ambikadutta, Uttaratantra, Pratisyayapratisedha-Adhyaya (24; 23). Varanasi: Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S159 Brief review of commonly used herbal drugs in ayurvedic management of chronic kidney disease

Shriti Agrawal, R. K. Joshi Department of Kayachikitsa, National Institute of Ayurveda, Jaipur, Rajasthan, India

Abstract

Chronic kidney disease (CKD) refers to a spectrum of different pathophysiologic processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate over many

REVIEW ARTICLE REVIEW years. CKD is recognized as a major health problem affecting approximately 14% of the United States population. Numbers of prevalent CKD patients are continuous rising, reflected in the growing elderly population and increasing numbers of patients with diabetes and hypertension. Unfortunately, from India, there is limited data on the prevalence of CKD. In India, diabetes and hypertension account for 40–60% of CKD cases. In this study CKD is chosen, as in present scenario the cost of dialysis is very high and cannot be afforded by every patient and understanding this by means of principles explained in Ayurveda is necessary to manage the disease and make the patient comfortable to perform his daily routine. CKD patients treated with Ayurvedic Herbs such as Punarnava and Gokshur may prolong dialysis time or reduce its frequency.

Key words: Chronic kidney disease, Gokshur, Punarnava

INTRODUCTION Stage GFR, ml/min per 1.73 m2 0 >90# enal disorders have always remained a major area of concern for physicians 1 >90* Rfor a long time. The chronic kidney 2 60–89 disease (CKD) is defined as a reduction 3 30–59 in kidney function over many years and is 4 15–29 characterized by anuria, dysuria, and retention 5 <15 of urine. The kidneys regulate the composition # and volume of blood, remove metabolic With risk factor for CKD. *With demonstrated kidney damage. CKD: Chronic kidney disease wastes in the urine, and help control the acid/base balance in the body. They activate The three most common causes of CKD are diabetes mellitus Vitamin D needed for calcium absorption and (40%), hypertension (30%), and glomerulonephritis (10%). produce erythropoietin needed for red-blood- Together, these cause approximately 75% of all adult cases. cell synthesis. Kidney also makes an enzyme, Various risk factors for CKD are hypertension, diabetes renin which affects blood pressure through mellitus, autoimmune diseases, elderly age, family history negative feedback. CKD is characteristically of renal disease, previous episode of acute kidney injury, the [1] a progressive disease. Reduction of kidney presence of proteinuria, abnormal urinary sediments, and function defined as a glomerular filtration structural abnormalities of the urinary tract. rate (GFR) <60 mL/min/1.73 m2 for 3 months or more with or without evidence of kidney Address for correspondence: damage.[2] Dr. Shriti Agrawal, M.D. Scholar, Department of Kayachikitsa, National Institute of Ayurveda, Jaipur, Based on recent guidelines of the National Rajasthan, India. Kidney Foundation[3] (Kidney Dialysis Phone: 8960587141. Outcomes Quality Initiatives), in which stages E-mail: [email protected] of CKD are described as follows:

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S160 Agrawal and Joshi: Brief review of commonly used herbal drugs in ayurvedic management of chronic kidney disease

A large number of chemicals in common use are potential while having the urge for micturition, and suppression of renal toxins. The prevalence of CKD is increasing the urge of micturition, disorders of wasting or malnutrition worldwide. Most chronic nephropathies lack a specific and severe traumatic injury.[6] In Charak samhita described treatment and progress relentlessly to end-stage renal that Kidney and bladder are the root (controlling organ) of disease. The prevalence of CKD is high in developing the channels carrying urine and fat, the opening of these countries. The prevalence of CKD was high in north and channels get affected by fat, mansa, and liquid dhatus of the southwest regions compared with other regions. As CKD is body. The vitiated doshas while coming in contact with the a morbid and costly disorder with a significant proportion of opening of these channels obstructs them. This results in the patients progressing to an end-stage renal disease requiring manifestation of kidney disease which becomes chronic or dialysis. On the contrary, the middle class/lower class cannot incurable due to the affection of all the qualities of doshas afford treatment such as regular dialysis and renal transplant. and also due to the simultaneous vitiation of homogenous Many people discontinue the treatment as they cannot afford and heterogenous dhatus.[7] The use of herbal drugs for the dialysis. prevention and treatment of various diseases is constantly developing throughout the world. Being an ancient science (the Upaveda of Atharvaveda), Ayurveda views Urinary system differently from the According to modern medical sciences, the causes of CKD modern medical science. Accordingly, three types of are many, but three most common causes of CKD are diabetes excretory products of the body, i.e., Purisha (Faeces), mellitus (40%), hypertension (30%), and glomerulonephritis Mootra (Urine), and Sweda (Sweat) are eliminated through (10%). Together, these cause approximately 75% of all adult three different routes, and for these three Malas, separate cases. The most frequent cause is diabetic nephropathy as the Srotas are described in our classical texts. According to the high levels of sugar damage the kidneys over several years, Ayurveda, waste products will be produced at the end of the and results in a reduced ability to filter blood and excrete metabolic activity of their described Srotas so as the Urine. waste products in the urine. Hypertensive nephropathy Every Srotas as the last part of its activities produces some is a common cause in elderly leads to damage of small amount of “Kleda” (waste metabolic product) which is blood vessels. When small blood vessels in the kidneys carried to the kidneys (Vrikkas) by Udak dhatu on one side that filter the blood are damaged, kidney failure results. while major part of urine is formed as the liquid fraction of Glomerulonephritis may cause a small output of urine, “Kitta” which is the end part of the process of digestion. the spilling of blood and protein into the urine, and body Pakvashya is the place where the Sar (useful) and Kitta swelling. Long-term or repeated kidney infections can also (waste) are differentiated, and the liquid formation of damage the structure of the kidneys, reducing the kidney’s [4] Kitta is absorbed by several “Mootravaha Nadis.” capacity to filter blood. According to the modern medicine, the “Pakvashya” is a large, water and electrolyte absorbing structure. The activity of substances produced by or traveling through Aims and objectives any system is divided into two parts, namely A) Poshaka (i.e., precursor) and B) Poshya (i.e., formed). The urinary In the present study CKD is chosen, as in present scenario system in Ayurveda can be explained by the Poshaka, peoples are not well aware about the importance of kidney for and Poshya concept as the Poshaka division of Urine is their health, so the study is chosen to raise awareness of the formed in the Pakvashaya itself, while Poshya-Poshaka importance of our kidneys to our overall health and to reduce fraction in the kidneys (Vrikkas). The role of Samana and the frequency and impact of kidney disease and its associated Apana Vayu is equally important in this process of Poshaka health problems worldwide. This study is done with an aim Mootra - Poshya Mootra transformation as Samanavayau to review the recent study done on some common herbs used travels all over the Kostha and leads to the formation of in India. Poshaka where Sookshmapachana (micro digestion) takes place, and the role of Apana Vayu is for the excretion of many substances.[5] MATERIALS AND METHODS

However, in Ayurvedic classical texts, there is no any clear This study is done by going through the literature search in description about the role of the kidney in the formation of the classical texts, and the pathogenesis of kidney disease urine. Ayurvedic texts have described the urinary system and various studies on herbs were obtained by searching by the name “Mootravaha Srotas” in all its basic texts. various medical research databases such as PubMed, Several diseases such as Ashmaree, Ashtheela, Mootraghat, Google Scholar, and other national research databases and Mootra vega dharana have been described in details and in the classical texts. The term entered for search by Aacharya Charaka, Sushruta, and Vagbhata in their is “CKD,” “chronic renal failure,” and “nephropathy,” texts along with treatment and diet regimen. According “nephroprotective drugs,” “renal disorder,” and to Acharya charak the causes of mootra dosha vikar are “nephrotoxic drugs.” Manual search was made by going vitiated by the intake of drinks and food, sexual intercourse through the reference list of retrieved articles to identify

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S161 Agrawal and Joshi: Brief review of commonly used herbal drugs in ayurvedic management of chronic kidney disease

Table 1: Mode of action of commonly used herbal drugs in management of chronic kidney disease Plant name Latin name Family Phytoactive constituents Mode of action Punarnava Boerhavia diffusa Nyctaginaceae Punarnavoside, liriodendrin Diuretic, anti‑inflammatory, syringaresinol, xanthone antifibrinolytic, antibacterial beta‑ecdysone properties Gokshura Tribulus terrestris Zygophyllaceae Nitrates, potassium salts Diuretic, anti‑inflammatory essential oil Mahanimba Melia azadirachta Meliaceae Ethanol extract Decrease the concentration of urea and creatinine Haridra Curcuma longa Zingiberaceae Curcumin Anti‑inflammatory, Increases the antioxidant activity Shallaki Boswellia serrata Burseraceae Boswellic acid Anti‑inflammatory Anantmool Hemidesmus Apocynaceae Aqueous and methanolic Reduces the level of indicus extracts microalbuminuria, serum urea, and creatinine relevant additional study. The study of various Ayurvedic Gokshura (Tribulus terrestris) also plays an important texts was made critically, and a review of the action of role in kidney disorders as it has diuretic property due to commonly used herbs in India had been made. large quantities of nitrates, potassium salts, and essential oil present in its fruits and seeds and its diuretic action is very useful in hypertensive patients. The ethanolic extract OBSERVATIONS AND DISCUSSIONS of Gokshura inhibits the expression of cyclooxygenase-2 and induces nitric oxide synthase in lipopolysaccharide- According to Acharya charak, Mootra Dosh Vikara is stimulated cells. It also suppressed the expression of pro- treatized by Punarnava, Gokshur, Pashanbheda, Kusha, inflammatory cytokines such as tumor necrosis factor-alpha Kash, etc.[8] and interleukin-4 in macrophage cell line. Hence, it has a beneficial effect on various inflammatory conditions.[12] Haritaki (Terminelia chebula) is used with Gomutra in edema (shotha) produced due to kidney disorders.[9] Mahanimba (Melia azadirachta) an experimental study was conducted ethanolic extract of M. azadirachta against Shilajeet used with Triphala Kwath is also helpful in Acetaminophen-induced nephrotoxicity in albino rats shows that oral administration of ethanol extract of M. azadirachta has alleviating the edema in kidney disorders.[10] significantly decreased the concentration of urea and creatinine. Based on this study, it can be concluded that the prolonged use Punarnava (Boerhavia diffusa) has the constituent of an extract of M. azadirachta decreases the renal disorder.[13] Punarnavoside is reported to have diuretic, anti-inflammatory, antifibrinolytic, and antibacterial properties. Of the two Various studies demonstrate that mild and moderate CKD is lignans Liriodendrin and Syringaresinol mono-β-D-glucoside associated with chronic inflammation and low antioxidant found in the root extract of Punarnava, liriodendrin has a activity. Systemic inflammation and impaired antioxidant significant calcium channel blocking effect. Calcium channel status may be greater in CKD populations with multiple antagonists or calcium channel blockers are drugs which relax comorbidities. Haridra (Curcuma longa) contains Curcumin the smooth muscle cells, thereby reducing muscle spasms. and Shallaki (Boswellia serrata) contain boswellic acid, so They relax blood vessels and lower blood pressure, which both are safe and tolerable and helped to improve the levels are useful in the treatment of kidney disorders produced due of an inflammatory cytokine.[14] to hypertension. The diuretic action of the herb is attributed to the presence of the xanthone beta-ecdysone. Punarnava Anantmool (Hemidesmus indicus) was found on study base also has antimicrobial, anti-inflammatory, and antispasmodic that aqueous and methanolic extracts have a more significant properties, which are beneficial in treating urinary tract inhibitory effect on saltwater feeding induced severity of disorders such as chronic and recurrent urinary tract infections microalbuminuria, serum urea and creatinine, myocyte (UTIs), including UTIs in pregnancy. The herb has been diameter and retention of sodium and water, and increases reported to increase serum protein levels and reduce urinary the serum calcium level. It is potent natural nephroprotective protein excretion in clinical trials in patients suffering with also a cardioprotective.[15] nephrotic syndrome. The activity is attributed to the presence of rotenoids in various parts of the plant. Punarnava also Kakmachi (Solanum nigrum) was found that renal markers reduces edema associated with kidney dysfunction.[11] (urea, serum creatinine, and uric acid) were brought back

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S162 Agrawal and Joshi: Brief review of commonly used herbal drugs in ayurvedic management of chronic kidney disease to normal. Thus, it is inferred that S. nigrum preserves the on Chakrapani Datta’s Ayurveda Dipika. Vol. II. Edition- functional capacity of the kidney against ethanol toxicity Reprint, Nidana Sthan, Ch. 4, Slok No 8. Varanasi: [Table 1].[16] Published by Choukhamba Sanskrit Series Office; 2010. p. 56. 8. Sastri PK, Chaturvedi GN. Agnivesa’s Caraka Samhita CONCLUSION Text Revised by Caraka and Drdhbala, Introduction by Shri Satya Narayana Sastri. Part I. Reprint, Sutra Sthana, According to Ayurveda CKD is a principal disorder which Ch. 4, Slok No 35. Varaansi: Published by Choukhamba is described in term of Mutra Dosh Vikar and mentioned Bharati Academy; 2011. p. 89. as a cause of edema. Treatment should be prescribed in 9. Sastri PK, Chaturvedi GN. Agnivesa’s Caraka Samhita both the conditions. Remedies should be diuretic and anti- Text Revised by Caraka and Drdhbala, Introduction by inflammatory as well as being electrolytes filtration. Shri Satya Narayana Sastri. Part II. Reprint, Chikitsa Sthana, Ch. 12. Slok No 21. Varaansi: Published by Choukhamba Bharati Academy; 2013. p. 35. REFERENCES 10. Sastri PK, Chaturvedi GN. Agnivesa’s Caraka Samhita Text Revised by Caraka and Drdhbala, Introduction by 1. Kidney Disease Statistics for the United States- Shri Satya Narayana Sastri. Part II. Reprint, Chikitsa National Institute of Diabetes and Digestive and Sthana. Ch. 12. Slok No 49. Varaansi: Published by Kidney Disease. Available from: https://www.niddk.nih. Choukhamba Bharati Academy; 2013. p. 365. gov›HealthInformation›HealthStatistics. [Last retrieved 11. Awasthi LP, Verma HN. Boerhavia diffusa–A wild herb on 2016 Dec 06]. with potent biological and antimicrobial properties. 2. Mathew KG, Aggrawal P. Medicine. 4th ed. Ch. 16. Asian Agrihist 2006;10:55-68. New Delhi: Published by Elsevier a Division of Reed 12. Chhatre S, Nesari T, Somani G, Kanchan D, Sathaye S. Elsevier India Private Limited.; 2012. p. 729. Phytopharmacological overview of Tribulus terrestris. 3. Fauci S, Kasper L, Longo L, Braunwald E, Hauser L, Pharmacog Rev 2014;8:45. Jameson L, et al. Harrison’s Principle of Internal 13. Srinivasan V, Panneerselvam R, Gunasekaran S, Medicine. 17th ed. Ch. 274. United States: Published by Palani S. Ethanolic extract of Melia azadirachta against McGraw-Hill Companies, Inc.; 2008. p. 1761. acetaminophen induced nephrotoxicity. Int J PharmTech 4. Ambikaduttashashtri K. Reprint, Sushruta Samhita. Res 2014;6:70-9. Part 1. Ch. 3. Slok No 21, 22. Varanasi: Published by 14. Moreillon JJ, Bowden RG, Deike E, Griggs J, Wilson R, Chaukhambha Sanskrit Sansthana, Nidanasthana; 2013. Shelmadine B, et al. The use of an anti-inflammatory p. 314. supplement in patients with chronic kidney disease. 5. Tripathi B. Ashtang Hridaya. Reprint, Sutrasthana. Ch. J Complement Integr Med 2013;10:632-8. 12. Slok No 8, 9. New Delhi: Published by Chaukhambha 15. Chidrawar VR, Ushir YV, Sudarshan S, Patel KN, Sanskrit Prakashan; 2014. p. 171, 172. Patel NJ, Vadalia KR. Possible role of natural 6. Sharma RK, Dash VB. Agnivesa’s Caraka Samhita nephroprotective; Hemidesmus indicus in congestive Text with English Translation and Critical Exposition heart failure. Pharmacog Res 2009;1:367. Based on Chakrapani Datta’s Ayurveda Dipika. Vol. 16. Sankaran M. Protective effect of Solanum nigrum fruit II. Edition-Reprint, Vimana Sthan. Ch. 5. Slok No 20. extract on the functional status of liver and kidney Varanasi: Published by Choukhamba Sanskrit Series against ethanol induced toxicity. J Biochem Technol Office,; 2010. p. 179. 2009;3:339-43. 7. Sharma RK, Dash VB. Agnivesa’s Caraka Samhita Text with English Translation and Critical Exposition Based Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S163 Medicinal use of ashwagandha (Withania somnifera) and its cultivation possibilities in Vindhyan Region, Uttar Pradesh, India

S. N. Singh, G. P. Singh, S. P. Singh, K. K. Maurya, Shree Ram Singh Department of Krishi Vigyan Kendra, Institute of Agricultural Sciences, Barkachha, Mirzapur-231001, Uttar Pradesh, India

Abstract

Ashwagandha (Withania somnifera) is also known as Indian ginseng. The roots of ashwagandha smell like horse

REVIEW ARTICLE REVIEW and it vitalizes body; its plant has been traditionally used in Indian medicines such as Ayurveda. It has been used for more than 3000 years, and also, its different plant parts, i.e., seeds, root, and leaves are used for preparing various drugs. Ashwagandha is a very powerful ancestral plant which has allowed it to persist through centuries of use to become one of best known in the world today. The crop is cultivated in many states, and Madhya Pradesh, Rajasthan, Punjab, Haryana, Uttar Pradesh, Gujarat, and Maharashtra are major growing states in India. The plant is hardy even in drought conditions and resistant to major pests and infestations. It can be cultivated equally as a rainfed and irrigated crop. Ashwagandha is grown in deep-rooted and well-drained sandy loam or red soil with good drainage facilities, having pH in the range of 6.5–8.0. Waterlogged and eroded soil is not suitable for cultivation, and good quality seeds on different varieties of ashwagandha should be used in cultivation.

Key words: Ashwagandha, medicinal plant, Vindhyan region

INTRODUCTION whitish brown roots. Flowers are greenish in color with orange-red berries. shwagandha (Withania somnifera) is also known as Indian ginseng. The Vindhyan region is a complex, alternating chain AThe roots of the plant have been of mountain ridges, hill ranges, highlands, and plateau traditionally used in Indian medicines such as escarpments in West Central India. The Vindhyan region Ayurveda and unani. Ashwagandha is called consists of the Vindhyan plateau and the hills in the southern winter cherry in English, Asgandh in Hindi, part of the state and lies between 23°52’ and 24°21’ N Ammukirankazangu in Tamil, Amangura in Latitude to 82°42’ and 88°24’ E Longitude. Most area Kannada, Asvagandhi in Telugu, and Trittavu in covered in Vindhyan region is basically undulated land and Malayalam. Ashwagandha is originated in India soil of this region is having low fertility and low organic and is used very often in Ayurvedic medicine. It carbon content, but most of the area has red lateritic soils has multiple medicinal property and used in the with often pronounced nodules locally called “Murram.” [1] oldest Indian medicine system in the world. The depth of the soil also varies, and much of the area has The name “Ashwagandha” is derived as its roots a soil depth of just a few centimeters. Deep and fertile soils smell like horse and it vitalizes body. It has been are often found in the valleys between folds of hills where used for more than 3000 years, and different the soil washed from hill slopes has accumulated. Hence, plant parts such as seeds, root, and leaves are the topography presents a contrast from bare rocky outcrops used for preparing various drugs. All the plant alternating with good deep soils. The climate of the area parts are credited with medicinal properties.[2] is characterized by a long and intensely hot summer, low Ashwagandha is a very powerful ancestral plant rainfall, and a short mild winter. The hot weather usually which has allowed it to persist through centuries of use to become one of best known in the Address for correspondence: world today. It is used for medicinal purpose S. N. Singh, Department of Krishi Vigyan Kendra, for stress reliever, to treat senile dysfunction, Institute of Agricultural Sciences, Barkachha, and also, to control anxiety, depression, phobia, Mirzapur-231001, Uttar Pradesh, India. schizophrenia, etc. It is a branching shrub with Phone: +91-9453791916. E-mail: [email protected] an average height of 30–120 cm with fleshy,

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S164 Singh, et al.: Medicinal use of ashwagandha and its cultivation begins from the middle of March and extends up to the 2. Jawahar Asgand-134: It is a very high alkaloid variety, break of the monsoon till June. The summer temperature grown in Madhya Pradesh. It is developed by Jawaharlal goes up to 48°C in May and June. However, the average Nehru Krishi Vishwavidyalaya. Plant height is short and temperature range varied from 80 to 34°C. The rainfall is known for its higher density planting. The crop yields varies from 750 mm to about 1150 mm. Most of the rainfall in 180 days with a total withanolide content of about occurs in June, July, and August. There is a little winter rain 0.30% in dry roots. also which occurs generally in January and February and is 3. Raj Vijay Ashwagandha-100: It is also developed by sometimes substantial, fairly regular as compared with other Jawaharlal Nehru Krishi Vishwavidyalaya, Madhya [3] part of the state. Vindhyan region shows good possibilities Pradesh. in the cultivation of Ashwagandha. This paper details about 4. Rakshita and Poshita: These are high yielding verities the cultivation and medicinal use of Ashwagandha on developed by CSIR-Central Institute of Medicinal and Vindhyan region of Uttar Pradesh, India. Aromatic Plant, Lucknow. 5. WSR: Developed by CSIR-Regional Research Laboratory, Jammu. AREAS UNDER CULTIVATION 6. Nagori: It is a local variety with feature of having starchy roots. The global demand compared to supply for roots of Ashwagandha is high, and hence, it provides sufficient scope to cultivate it on commercial scale. The crop is cultivated in different states in which Madhya Pradesh, SEEDS AND SOWING Rajasthan, Punjab, Haryana, Uttar Pradesh, Gujarat, and For good quality crop, seeds of different varieties of Maharashtra are major growing states in India.[4] The plant is hardy even in drought conditions and resistant to major Ashwagandha are used in cultivation and 4–5 kg seed is pests and infestations. It can be cultivated equally as a used per acre. To protect crop from seed borne disease and rainfed and irrigated crop. pest, before sowing, do treatment with thiram or dithane M-45 (Indofil M-45) at 3 g/kg of seeds. After treatment, the seeds are then air dried and used for sowing. Spacing of FIELD PREPARATION the Ashwagandha plantation depends on the growth habit and germination percentage of seed, normal spacing used Ashwagandha is generally grown in deep-rooted and well- for Ashwagandha plantation is about 20–25 cm line-to-line drained sandy loam or red soil with good drainage having distance 10 cm plant to plant distance, and seeds are usually pH in the range of 6.5–8.0. Waterlogged and eroded soil sown about 1–3 cm deep. is not suitable for cultivation of Ashwagandha. The soil should be loose, deep and black or heavy soils having good drainage are also suitable for cultivation of Ashwagandha. NURSERY MANAGEMENT AND Land preparation for Ashwagandha plantation is done in TRANSPLANTING April–May; it requires well pulverized and leveled soil. For fine tilth, the field is ploughed 2–3 times and ploughing or Before transplanting, field must be ploughed by Mould harrowing should be done before rains. Spread 10-20 tones Board Plough and harrowed twice to bring the soil in fine of farm yard manure, 15 kg of nitrogen and 15 kg phosphorus tilth and fill the soil with plenty of organic matter to nourish per ha required as a nutrient dose to the soil. At the time of the soil. Treated seeds are sown on raised nursery bed. The land preparation, FYM should be mixed with soil, and then seeds germinate in 5–7 days and are ready for transplantation the field is leveled with planking. There is no use of chemical in about 35 days. The water is applied in appropriate amount fertilizers and pesticides as it is a medicinal plant and grows before transplanting so that seedling can be easily uprooted. through organic sources. Some organic sources such as FYM, Nursery of Ashwagandha is prepared in June–July. vermicompost, green manure, concentrated organic manures, and crop residues are used as per requirement. Irrigation

VARIETIES OF ASHWAGANDHA Excess irrigation may harm the crops. If rainfall is heavy, then irrigation is not required otherwise 1 or 2 times irrigation is 1. Jawahar Asgand-20: High alkaloid variety, developed necessary in the crops. Under irrigated conditions, the crop by Jawaharlal Nehru Krishi Vishwavidyalaya, Madhya can be irrigated 1 time in 10–15 days. First irrigation should Pradesh. These are short plant height and grow in higher be given after 30–35 days from germination, and then, planting density. The crop yields in 180 days with a total second irrigation is provided after 60–70 days from first withanolide content of about 0.30% in dry roots. irrigation.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S165 Singh, et al.: Medicinal use of ashwagandha and its cultivation

PLANT PROTECTION Sitoindosides and acylsterylglucosides are anti-stress agents. Active principles of ashwagandha, for instance, the Weed control sitoindosides VII-X and withaferin-A, have been shown to have significant anti-stress activity against acute models of Normally two weddings are done to maintain the field free experimental stress. from weeds. First wedding is done in 20–25 days of sowing and second wedding after 20–25 days of first weeding. The dose of isoproturon 1.5/kg and glyphosate 1.5/kg should be MEDICINAL USE used before sowing the seeds to control the weeds. The leaves of ashwagandha plant has anti-inflammatory, hepatoprotective, and antibacterial properties and used for Aphids treating several health problems such as tumors, tuberculous gland, swelling, inflammation, boils, conjunctivitis, and It is a small bug which feeds by sucking sap from plants. blood purification. Its leaves are also very good for weight They reproduce rapidly and cause extensive damage to loss. The plant is being extensively used in traditional system plants. Imidacloprid 18.5% SL as foliar spray at 10-15 days of medicine for treating many ailments of animals and interval should be applied. humans.[6].

Shoot borer Diuretic activities are shown by fruits and seeds of plant, and roots of plants[7] are numerable pharmacological properties This insect belongs to Lepidoptera order. It is creamy in color and below are listed some of them: with brown head and mainly infests leaf and shoot of a young • Analgesic: Relieve pain. mature plant. This borer can be controlled with the spray of • Antianemic: Treat or to prevent anemia. indoxacarb 14.5 SC at 0.5 ml/L. • Adaptogen: Substance considered helping the body adapt to stress. • Anti-inflammatory: Reducing inflammation by acting on Disease and their control body mechanisms. • Antioxidant: Neutralize the oxidant effect of free radicals Diseases such as seedling rot, leaf spot, and blight are seen and other substances. in crop. To prevent from these diseases, it should be sprayed • Antitumor: Inhibiting the growth of a tumor or tumors. with dithane M-45 at of 3g/L of water, when crop is 30 days • Antidepressant: Prevent or treat depression. old and the spray should be repeated at 15 days interval if the • Aphrodisiac: Stimulates sexual desire. diseases persist. • Immunomodulatory: Modifies the immune response or the functioning of the immune system. • Phytoestrogen: Plant-derived estrogens not generated HARVESTING AND STORAGE within the endocrine system but consumed by eating phytoestrogenic plants. Plant starts yielding 160–180 days. Harvesting is complete • Reproductive tonic: Tonic for reproductive organs. in the dry weather when leaves are drying and berries change • Sedative: Promoting calm or inducing sleep. its color into red–orange. Harvesting is finished by hands by • Tonic: Restore or improve health or well-being. uprooting the whole plant or through machines such as power tiller without damaging the roots. The roots are removed from the plant and cut into smaller pieces, i.e., 8–10 cm in HEALTH BENEFITS length, and then, it is air dried and graded. The root pieces are stored in tin containers for sale. The higher the length of root • It is natural antioxidant. pieces, the higher it will fetch the price. Berries are plucked • It supports better sleep. separately, and then, they are air dried and crushed so as to • It improves energy level. take out the seeds. • It stabilizes on blood sugar and lowers cholesterol. • It helps to reduce the level of stress and tension. • It increases hemoglobin (red blood count) and hair CHEMICAL COMPOSITION melanin. • It helps to lower blood pressure and is highly effective in Whole plant of ashwagandha contains different chemical stopping the formation of stress-induced ulcers. compounds, and Whole plant of Ashwagandha contains • Ashwagandha is anabolic in effect and mainly considered different phyto chemical compounds includes alkaloids to help in weight gain. (isopelletierine, anaferine, cuseohygrine, anahygrine,[5] • It also helps to lose weight by reducing swelling in body Steroidal lactones (withanolides, withaferins) and saponins, and improving hemoglobin level.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S166 Singh, et al.: Medicinal use of ashwagandha and its cultivation

• It is a tonic that nourishes the whole body. In weakness, REFERENCES low body weight, emaciation, deficient hemoglobin, anemia, post convalescent weakness, and such other 1. Umadevi M, Rajeswari R, Rahale CS, Venkadesh SS, condition, its use gives good result. Pushpa R, Kumar KP, et al. Coimbatore traditional • It is useful for any imbalance in the muscles as it reduces and medicinal uses of Withania somnifera. Pharm Inov inflammation and strengthens muscles. 2012;1:102-10. • It improves body immunity and strengthens body defense 2. Singh S, Kumar S. Withania Somnifera: The Indian system. Ginseng Ashwagandha. Vol. 6. Lucknow: Central • It gives good results in nerve-related conditions such Institute of Medicinal and Aromatic Plants; 1998. p. 293. as multiple sclerosis, neurosis, insomnia, anxiety, and 3. Dubey P, Mishra P, Srivastava RJ, Burfal BS, Dixit RK. stress. Technology to Conserve Biodiversity of Vindhyan • It is used to enhance memory and lesson age-related Region. Proceeding International Symposium Tropical cognitive deficits. Forestry Research: Challenges in the New Millennium; • It may help prevent tolerance and dependence with 2001. p. 59-61. morphine. 4. Rishikesh AH, Sarika FA, Amol SR, Sunil GS, Kumar SR, Dighe CS. Maharashtra micropropagation of CONCLUSION Ashwagandha (Withania somnifera) Biosci Biotech Res Comm 2016;9:88-3. The Vindhyan region of Uttar Pradesh has rich medicinal 5. Rao BR, Rajput DK, Naguraju G, Adinarayana G. wealth, which has got wonderful commercial national as Hyderabad opportunities and challenges in the well as global potentials. This region is a native of many cultivation of Ashwagandha {Withania somnifera (L.) important medicinal plants and has a great potential for Dunal}. J Pharmacog 2012;3:88-1. their conservation and cultivation. Hence, the cultivation of 6. Rajakumar N, Shivanna MB. Traditional veterinary Ashwagandha can be promoted in this region, in conjunction healthcare practices in Shimoga districts of Karnataka, with marked facilities for the product. However, there are India. Indian J Trad Knowl 2012;11:283-7. many challenges such as price fluctuations of roots, limited 7. Narendra S, Moti B, De Prasant J, Gilca M. An exports by companies, long duration of the crop, low root overview on Ashwagandha: A rasayana (Rejuvenator) yields, high fiber content of the roots in some locations, of ayurveda. Afr J Tradit Complement Alter Med and long-term storage of roots. These challenges may be 2011;8 5 Suppl:208-13. overcome, by policy formation for promoting medicinal plants and providing skills to farmers for advanced methods of cultivation practices and use of high-yielding varieties. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S167 Pharmacognostical and phytochemical evaluation of Tephrosia purpurea (Linn.) Pers.

Snehal Kumari1, Anupriya Singh1, Dev Nath Singh Gautam2, Narendra Kumar Singh1 1Department of Pharmacy Ayurveda, Ayurvedic Pharmacy Research Laboratory , Rajiv Gandhi South Campus, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Barkachha, Mirzapur, Uttar Pradesh, India, 2Department of Rasa Shastra, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

ORIGINAL ARTICLE ORIGINAL The plant Tephrosia purpurea (Linn.) Pers. belonging to the family Fabaceae, reach in prenylated flavonoids, is used by the several ethnic groups for its anthelmintic activity. It is also described in traditional medicine for the treatment of splenomegaly and hepatic disorders. This present study was performed for the identification of the plant by macroscopical, microscopical, physicochemical, and quantitative study using standard methods. Characters of leaf are, namely, erect, nerved, entire, oblanceolate in shape and 7–10 cm long, 11–15 leaflets (2–2.8 cm × 0.8–1.2 cm), and one terminal leaflet at the appendage. 7–12 mm long petioles, cuneate base, having aromatic, characteristic odor, and unpleasant bitter taste were found in macroscopical study. The unicellular trichomes, uniform cuticle, palisade cells, and collateral type vascular bundle were observed in the transverse section (T.S.) of leaflet. The sclerenchymatous cells, medullary rays, and lignified xylem were observed in the T.S. of stem and root. The calcium oxalate crystals were observed in the pith region of the section of stem. Fluorescence study, ash, extractive, saponification, and acid values were estimated as per the WHO guidelines. The presence of secondary metabolites such as flavonoids, proteins, carbohydrate, steroids/terpene, and phenolics was confirmed, and concentration of heavy metals was also measured. The present study was performed to compile the suitable monograph for the identification and to ensure the purity of crude material of T. purpurea (Linn.) Pers.

Key words: Tephrosia purpurea, Sharapunkha, Isoflavones, Chalcones

INTRODUCTION of prenylated flavonoids.[4-6] Phytochemical screening of the plant shows the presence of rotenoids, isoflavones, flavanones, ephrosia purpurea (Linn.) Pers. belongs chalcones, sterols, flavonols, and flavones.[7] The whole plant to the family Fabaceae, its English name is anthelmintic, alexeteric, antipyretic, use in liver diseases, is “Purple Tephrosia” or “Wild indigo,” and spleen, heart, blood, cures tumors, ulcers, leprosy, asthma, T bronchitis, piles, caries of teeth, and used internally as a blood in Sanskrit known as Sharapunkha is a highly branched, suberect, and herbaceous perennial purifier. In Ceylon, it is employed as an anthelmintic for [8] [9] herb. In Ayurvedic literature, it is named as “Sarwa children. Infusion of seed is used as anthelmintic oil. Seeds wranvishapaka” which means it has property oil used to treat eczematous itching, scabies, and for other skin [10] of healing all types of wounds.[1] The generic disease. Seeds also used for piles, gonorrhea, and syphilis. name T. purpurea is derived from the Greek word tephros, means “ash-colored,” giving the grayish tint on to the leaves. Tephrosia is a genus Address for correspondence: of flowering plants in the pea family, Fabaceae, Dr. Narendra Kumar Singh, having more than 400 species.[2] It is the native Ayurvedic Pharmacy Research Laboratory, plant of Africa, Southeast Asia to Australia, Rajiv Gandhi South Campus, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Western part of Pacific, China, Sri Lanka, Barkachha, Mirzapur - 231 001, Uttar Pradesh, India. and India. In India, Andhra Pradesh, Haryana, Phone: +91-9956749674. Rajasthan, and Tamil Nadu are the places where E-mail: [email protected] T. purpurea found.[3] This genus has rich amount

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S168 Kumari, et al.: Pharmacognosy of Tephrosia purpurea

MATERIALS AND METHODS Foreign matter determination The seeds of plant (250 g) were spread uniformly in the Plant Material form of a thin layer without overlapping. The sample was inspected using magnifying lens (6×). Foreign matter was Whole plant (fresh) and seeds of T. purpurea were collected separated manually. After whole examination of sample, the from the Rajiv Gandhi South Campus, Banaras Hindu foreign matter was weighed and percentage w/w present in University, Mirzapur, Uttar Pradesh, India, in September the sample was calculated.[15] month and whole plant specimen was authenticated at Botanical Survey of India, Howrah, West Bengal, India Fluorescence analysis of powdered drug (plant identification letter: CNH/2017/Tech.II/48, speciemen Fluorescence characteristic was carried out by treating the No. SK-01, Dated: 17-10-2017). coarse powder of T. purpurea seeds with different reagents and observing in the visible light, short UV (254 nm), and Preparation of Plant Extract long UV (366 nm).[16]

The collected seeds of T. purpurea were dried well and coarsely powdered with mechanical grinder, then sieved Phytochemical Evaluation through 20 #. 5 g coarse powder was successively extracted by cold maceration process with 100 mL each of petroleum Preliminary phytochemical screening ether, chloroform, alcohol, and water by shaking continuously Presences of various phytochemical constituents were [11] for 6 h and allowed to stand for 18 h. All the different analyzed by preliminary phytochemical screening methods. extracts were filtered and concentrated under reduced For the detection of secondary metabolites such as alkaloids, pressure in rotary evaporator (Perfit India, Pvt. Ltd.) below carbohydrate, glycosides, saponins, terpenoids, phenolics, 60°C and stored in a desiccators until its use. steroids, and flavonoids, and protein different extracts, namely, petroleum ether extract, chloroform extract, ethyl Pharmacognostical Evaluation acetate extract, methanol extract, and aqueous extract of T. purpurea seeds were used.[12,17] Powder study Thin-layer chromatography (TLC) For the powder study, small amount of powder was stained with phloroglucinol:HCl (1:1), observed under microscope TLC was used for the further confirmation of secondary and pictures were taken at different magnifications.[12] metabolites in the various crude extracts of seeds.[18] TLC

was performed using silica gel 60 F254 as stationary phase Macroscopical, microscopic, and powder evaluation and various compositions of different organic solvents with varying polarity were used as mobile phases to develop The macroscopical evaluation of the whole plant parts, namely, chromatogram. For the detection of components, various leaf, stem, and roots of T. purpurea was performed by studying visualizing reagents including Dragendorff’s reagent the different organoleptic characters such as size, shape, (alkaloids), benzidine and sodium metaperiodate (glycosides/ color, surface characteristics, odor, taste, and texture. For the microscopical studies, free-hand sections of the fresh leaf, stem, sugars), Liebermann–Burchard reagent (saponins/sterols/ and root of plant were taken and washed with chloral hydrate. terpenoids), 5% ferric chloride (phenolics), and Sinoda The sections were immersed into absolute alcohol to dehydrate reagent (flavonoids) were used. and stained with phloroglucinol and conc. hydrochloric acid (1:1 v/v) and finally mounted with glycerin on slides and Quantitative estimation of heavy metals observed under Nikon trinocular digital microscope (Eclipse Heavy metals Zn, Cd, and Pb were quantitatively estimated E200). Images were captured at different magnifications.[13,14] in the powdered seeds of T. purpurea,[19] using atomic absorption spectrophotometer (Shimadzu-AA6300). Determination of physicochemical parameter Physicochemical standardization of seeds powder of T. purpurea was done using several parameters, namely, total RESULTS ash value, acid-insoluble ash value, water-soluble ash value, loss on drying, and foreign matter, extractive values in organic Pharmacognostical Evaluation solvents such as alcohol, chloroform, water, petroleum ether, foaming index, and swelling index, while saponification Morphological evaluation value and acid value were estimated using petroleum ether extract. All these standardization parameters were performed Leaves of the plant were found to be erect, nerved, entire, as per the WHO guidelines.[15] lanceolate in shape and 7–10 cm long having 11–15 leaflets

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S169 Kumari, et al.: Pharmacognosy of Tephrosia purpurea

(2–2.8 cm × 0.8–1.2 cm), and one terminal leaflet at the Fluorescence powder drug analysis appendage. Upper surface was dark grayish-green, glabrous, The results of the fluorescence analysis of seeds powder of while lower surface was light in color than upper having fine the plant in day light (visible light), short UV light (λmax hairs. Length of petioles was 7–12 mm, cuneate base, and ascending slender. Leaves have aromatic, characteristic odor, and unpleasant bitter taste. Leaflets form tongue-shaped structure Table 1: Physicochemical feature of T. purpurea when break by stretched longitudinally. Seeds were light brown seeds in color having dark brown spots. The stem was cylindrical, Physicochemical parameters Results brown colored, woody, branched, bitter in taste, and odorless. Foreign matter Not >1.0% (w/w) Roots were small, pale yellow, cylindrical, odorless, and bitter in Loss on drying Not >0.5% (w/w) taste having many root hairs and small roots [Figure 1]. Acid value Not <8.75 Saponification value Not <287.51 Microscopical evaluation Ash value In the T.S., leaflet showed uniform cuticle or isobilateral Total ash value Not >11.26% (w/w) in nature. The upper epidermis, mesophyll tissue, and Acid‑insoluble ash value Not >2.5% (w/w) lower epidermis were present in the lamina portion. Upper epidermis of lamina containing tangentially elongated Water‑soluble ash value Not >10.98% (w/w) single layer of cells is covered with cuticle. Upper palisade Extractive value has 2–4 layers of palisade cells while lower has 2–5 layers. Water‑soluble extractive value Not <20.65% (w/w) Spongy parenchymatous cells loosely arranged in between Alcohol‑soluble extractive value Not <2.85% (w/w) the upper and lower palisade consist of vascular bundle. The Chloroform‑soluble extractive value Not <6.84% (w/w) uniseriate, covering trichomes were present on lower and upper epidermis. The upper epidermis is less convex than Petroleum ether‑soluble Not <12% (w/w) extractive value lower epidermal part of midrib. The midrib part consists of collateral type of vascular bundle surrounding spongy Foaming index Not <100 parenchymatous cells. The vascular bundle is arc shaped Fiber content Not <6.18% having spiral xylem vessels [Figure 2]. Swelling index <0.5% Heavy metals The T.S. of the stem observed having elongated epidermal Lead (Pb) 0.1941 ppm layer, was covered with cuticle. Layers of parenchymatous cells were present after the epidermis. Lignified Cadmium (Cd) 0.0050 ppm sclerenchymatous cells were also found in cortex region. Zinc (Zn) 1.5045 ppm Bicollateral vascular bundles were situated beneath the cortex T. purpurea: Tephrosia purpurea having lignified xylem. Medullary rays were uniseriate type present with the xylem. The pith occupied the central portion containing calcium oxalate crystals and no intercellular spaces [Figure 2].

In the same fashion, T.S. of root was also found to contain epidermal layer, which was made up of irregular compact cork cells. After the epidermis, cortex containing collateral arrangement of xylem and phloem (vascular bundle) with a b c lignified xylem observed. A thin layer of phloem found Figure 1: Dorsal and ventral view of leaf (a), stem (b), and root (c) surrounding the xylem. The medullary rays were spreaded in the whole central part [Figure 2].

Microscopical study of powder of whole plant showed the presence of unlignified multicellular covering trichomes, fragments of leaf epidermis, compressed cork cells of root, fragments of pitted xylem vessel, tracheids, and fibers. a b c Figure 2: Transverse section of leaf (a), stem (b), and root (c) of Physicochemical characteristic Tephrosia purpurea. UE: Upper epidermis, LE: Lower epidermis, Ep: Epidermis, UP: Upper palisade cell, LP: Lower palisade cell, The results of physicochemical standardization parameters Sc: Sclerenchymatous cell, Ph: Phloem, Xy: Xylem, Mr: Medullary represented as in Table 1. ray, Pi: Pith, T: Trichome, C: Calcium oxalate crystals

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S170 Kumari, et al.: Pharmacognosy of Tephrosia purpurea

[20] Table 2: Fluorescence powder drug analysis of seed with modern medicine. Leaves are the photosynthetic of T. purpurea machinery and constitute the several metabolites of the plants. Seeds, stem, and roots are also important source of Powder + Reagent Visible 254 365 nm bioactive compounds. Morphological and microscopical light nm evaluation of leaves, stem, and roots reveals the different Powder as such Mustard NF Lime characters and special arrangements of various types of cells Powder + 1 N NaOH Lemon NF Pea soup to constitute the plant tissue which are presented in results. in water In the evaluation of physicochemical parameters, the total Powder + 1 N NaOH Lime NF Silver ash value was approximately 4 times more than acid- in MeOH insoluble ash and water-soluble ash indicating the presence Powder + 1 N HCl in Colorless NF Mint of inorganic and silica components in the seed powder. water [15] The water-soluble extractive value was the highest Powder + 1 N HCl in Colorless NF Apple green value and petroleum ether-soluble extractive value was MeOH the second highest extractive value. Chloroform-soluble extractive was 3 times more than alcohol but less than water Powder + 1 N HNO3 Sand color NF Kiwi green in MeOH and petroleum ether extractive values. The seed powder was found to contain steroid, phenolics and flavonoids in Powder + 1 N HNO3 Mustard NF Dark green in water various extracts. Preliminary phytochemical screening revealed the presence of high amount of carbohydrate and Powder + I2 (5%) Dark NF NF brown proteins in aqueous extract. Petroleum ether extract of T. purpurea seeds was found to contain free acids and fatty Powder + FeCl (5%) Dark olive NF NF 3 acids resulting acid value and saponification value 8.75 green and 287.51, respectively. In the quantitative analysis of Powder + KOH Colorless NF Lime green heavy metal, the concentration of lead (Pb) and cadmium

Powder + NH3 (25%) Nut brown NF Lime green (Cd) was 0.1941 ppm and 0.0050 ppm, respectively, is Powder + acetic acid Colorless NF Grass green very low concentration than zinc (Zn) which was present in NF: No fluorescence, T. purpurea: Tephrosia purpurea 1.5045 ppm concentration.

T. purpurea is described in Vedic literature for the treatment Table 3: Preliminary phytochemical screening and of scrofula, wound, rat poisoning, splenomegaly and use thin‑layer chromatography of T. purpurea seed extracts to expel worms from abdomen, and several preparations Phytoconstituents Various extracts of T. purpurea for different health problems.[21] It is also described for seeds hepatic disorders, and seed oil used for the treatment W. E. A. E. C. E. P. E. E. of skin disease.[22] T. purpurea plant used by different Alkaloids ‑ ‑ ‑ ‑ ethnic groups for the treatment of several diseases, so it Steroids/terpenes + + is important to standardize the plant. The reported data in this study for T. purpurea, namely, pharmacognostic Saponin + ‑ ‑ ‑ features, values of physicochemical standardization, and Phenolic compound +++ +++ + + quantitative estimations will help to compile the suitable Carbohydrate +++ + ‑ ‑ monograph for its identification and to ensure the purity Protein +++ + ‑ ‑ of this drug. Flavonoids + ++ Starch ‑ ‑ ‑ ‑ CONCLUSION W.E.: Water extract, A.E.: Alcoholic extract, C.E.: Chloroform extract, P.E.E.: Petroleum ether extract. (+), (++), and (+++) indicate the presence of phytoconstituents in higher, moderate, The plant T. purpurea is used by different ethnic groups for the and lower amount, respectively. (–) indicates the absence of treatment of several diseases. The whole plant is anthelmintic, phytoconstituents. T. purpurea: Tephrosia purpurea alexeteric, antipyretic, use in liver diseases, spleen, heart, blood, cures tumors, ulcers, leprosy, asthma, bronchitis, 254 nm), and long UV light (λmax 365 nm) are expressed in piles, caries of teeth, and used internally as a blood purifier. Tables 2 and 3. In the present study, pharmacognostical and physicochemical standardization of T. purpurea were performed. Tephrosia is a genus of flowering plants in the pea family, Fabaceae, having DISCUSSION more than 400 species. Standardization parameters developed in the present study will be helpful in the identification and The plant-derived medicines have less adverse effects, authentication of T. purpurea as well as to differentiate with more therapeutic activity and safe to use, if compared other species of genus Tephrosia.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S171 Kumari, et al.: Pharmacognosy of Tephrosia purpurea

ACKNOWLEDGMENT system. Int J Recent Adv Pharm Res 2013;3:12-22. 11. Anonymous. The Ayurvedic Pharmacopoeia of India. Authors are thankful to R. Gogoi, Botanical Survey of India, Part-II. 1st ed., Vol. I. New Delhi: Ministry of Health and Howrah, West Bengal, India, for proper identification and to Family Welfare, Govt. of India; 2007. p.191. authenticate the plant specimen. 12. Khandelwal KR. Practical Pharmacognosy.18th ed. Pune: Nirali Prakashan; 2001. 13. Kokate CK, Purohit AP. A Text Book of Pharmacognosy. REFERENCES Pune (India): Nirali Prakashan; 2006. 14. Johansen DA. Plant Microtechnique. London: McGraw- 1. Despande SE, Shah GB, Parmar NS. Anti-ulcer activity Hill Publishing Company, Ltd.; 1940. p. 182. of Tephrosia purpurea in rats. Indian J Pharmacol 15. Anonymous. Quality Control Methods for Medicinal 2003;35:168-72. Plant Materials. Geneva: World Health Organization; 2002. p. 115. 2. Quattrocchi U. CRC World Dictionary of Plant 16. Chase CR, Pratt RJ. Fluorescence of powdered vegetable Names: Common Names, Scientific Names, Eponyms, drugs with particular reference to development of a system Synonyms and Etymology. Vol. 4. Boca Raton: CRC of identification. J Am Pharm Assoc 1949;38:324-31. Press; 2000. p. 2642. 17. Harbone JB. Phytochemical Methods. 3rd ed. London: 3. Orwa C, Mutua A, Kindt R, Jamnadass R, Simons A. Chapman Hall; 1984. Agroforestree Database: A Tree Reference and Selection 18. Wagner H, Bladt S. Plant Drug Analysis: A Thin Layer Guide Version 4.0 World Agroforestry Centre. Vol. 27. Chromatography Atlas. 2nd ed. New York: Springer- Nairobi, Kenya: CGIAR; 2009. p. 52-9. Verlag Berlin Heidelberg; 1984. 4. Geesink R. Advances in Legume Systematics. Part 1. 19. Gomez MR, Cerutti S, Sombra LL, Silva MF, Martinez LD. London: Royal Botanic Gardens, Kew; 1981. p. 245-60. Determination of heavy metals for the quality control in 5. Ambasta SP. The Useful Plants of India. New Delhi Argentinean herbal medicines by ETAAS and ICP-OES. (India): CSIR; 1986. Food Chem Toxicol 2007;45:1060-4. 6. Saldanha CJ, Singh BG. Flora of Karnataka. Vol. 1. 20. Muniappan A, Savarimuthu I. Ethnobotanical London: Oxford and IBH Press; 1984. p. 495-9. survey of medicinal plants commonly used by Kani 7. Gupta RK, Krishnamurti M, Parthasarathi J. Purpurin: tribals in Tirunelveli hills of Western Ghats, India. A new flavanone from Tephrosia purpurea seeds. J Ethnopharmacol 2011;134:851-64. J Phytochem 1980;19:1264. 21. Sharma PV. Classical Uses of Medicinal Plants. 1st ed. nd 8. Kirtikar KR, Basu BD. Indian Medicinal Plants. 2 ed., Varanasi (India): Chaukhambha visvabharti; 1996. p. 359-60. Vol. 1. Dehradun: International Book Distributors and 22. Mishra S, Vaisya R. Bhavprakash of Shribhav Mishra Publishers; 1996. p. 724-5. Including Bhavprakash Nighantu portion Edited with 9. Anonymous. The British Pharmacopoeia. Vol. 8. the ‘Vidyotini’ Hindi Commentary, Notes and Appendix. United Kingdom: Published by the Stationary Office First Part. 11th ed., Varanasi (India): Chaukhamba on Behalf of the Medicines and Health Care Products. Sanskrit Bhavan; 2007. p. 407-8. Regulatory agency (MHRA); 2009. p. 1456-60. 10. Sharma R, Mehan S, Kalra S, Khanna D. Tephrosia purpurea-A magical herb with blessing in human biological Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S172 Shigrupunarnavadi lepa reduces the local reactions in keeta visha

K. Shobha Bhat Department of Agadatantra, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

Aim: Clinical evaluation of the efficacy of Shigrupunarnavaadi lepa on the four cardinal local reactions of Keeta Visha (insect bites). Materials and Methods: The study employed a single arm before-after clinical trial design. A sample of 30 subjects who had a history of insect bite or sting and presenting with the four cardinal symptoms- pain, itching, redness and swelling were enrolled into the study. Shigrupunarnavaadi lepa was applied externally on the bite site, twice daily for 5 days. These four symptoms were clinically graded before and after the application of the ORIGINAL ARTICLE ORIGINAL drug. Results and Discussions: Ruja (Pain) in the subjects showed an improvement of 76.59%, Kandu (itching) 58.75%, raga (redness) 54.16% and shopha (swelling) 81.03% respectively. Conclusion: Sigrupunarnavaadi Lepa helps to reduce the local reactions including - pain, itching, redness and swelling and hence can be recommended as external application in the management of Keeta Visha.

Key words: Insect bites, keeta visha, Shigrupunarnavadi lepa, vhishaja shopha

INTRODUCTION which is movable, drooping down, quickly manifesting and causing burning sensation, and pain.[4] Apart from edema, the here are millions of insect species in the local reactions of keeta visha include raga (redness), strava world occupying virtually every possible (discharge), and vedana (pain).[5] ecological niche. The largest phylum T [6] “Arthropoda” consists of three subphyla, Shigrupunarnavadi lepa mentioned in Prayoga samucchaya, comprising of nine classes. In the arthropod a textbook of Keraleeya Visha Chikitsa, is traditionally class, insecta is the largest, containing used for toxic edematous conditions and is found to be thousands of species. Apidae, bombidae (bees), very effective in insect-bite associated with edema. This vespidae (wasps), and formicidae (ants) are the paper intends to discuss the effect of external application of important species that molest man. The range Shigrupunarnavaadi lepa on local reactions of keeta visha. of disorders caused by arthropods varies from mild local reactions due to bites and stings to severe systemic reactions or even death.[1] METHODOLOGY

Ayurveda explains shopha or edema to be of The study employed a single arm before-after clinical trial exogenous and endogenous verities. The causes design. A sample of 30 participants attending the outpatient of exogenous type of edema are affliction of department of visha chikitsa, who had a history of insect bite the external skin by the impact of wood, stone, or sting with acute toxicity with a maximum duration of 72 h weapon, fire, and poison. Edema due to insect and between the age group of 10–70 years were enrolled bite, hence, is classified under the exogenous [2] into the study. Patients with fatal conditions such as coma edema or Aagantu Shopha. Toxic edema or and convulsions, following the bite, or with complications vhishaja shopha is produced by crawling or due to the presence of sting were excluded from the study. urinating of insects over the body, injured by Informed consent from each participant was obtained. The 30 tusks, teeth, or claws of poisonous animals or even by the contact of excreta, urine, or semen; Author for correspondence: or of cloth contaminated by these or of even Dr. K. Shobha Bhat, Department of Agadatantra, non-poisonous animals; touch of poisonous Faculty of Ayurveda, Institute of Medical Sciences, trees, exposure to polluted air, wind, and Banaras Hindu University, Varanasi – 221 005, Uttar rubbing of artificial poisons.[3] The signs and Pradesh, India. E-mail: [email protected] symptoms of toxic edema include soft swelling

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S173 Bhat: Shigrupunarnavaadi lepa reduces the local reactions in Keeta visha participants were treated with trial drug-Shigrupunarnavadi 3. Continuous but not disturbing the patient in any way. lepa. 4. Pain disturbing some physical activities of the patient. 5. Excruciating pain disturbing routine and sleep.

DETAILS OF THE DRUG Itching 1. No itching. The drugs in Shigrupunarnavadi lepa were included in the study: 2. Mild itching, at the bite sight, found only immediately after the bite. Shigru (Moringa oleifera), Punarnava (Boerhavia diffusa), 3. Mild itching, at the bite sight, found for a few hours after Haridra (Curcuma longa), Vacha (Acorus calamus), Chandana the bite. (Santalum album), Patha (Cyclea peltata), Eswara Mooli 4. Moderate itching, at the bite sight, found for a few hours (Aristolochia indica), Yashti (Glycyrrhiza glabra), Shireesha after the bite. (Albizia lebbeck), and Gokshura (Tribulus terrestris). 5. Continuous and severe itching, at the bite sight, found for a few hours after the bite affecting the routine activity. Preparation of the Choorna Redness The above-mentioned fresh drugs after identification, 1. No redness collection, and cleaning with normal water were dried for 2. Slight color change, only at the point of bite, not well 7 days. They were then converted to Sookshma choornam appreciable. (fine powder) and used for the study. 3. Slight color change, in surrounding area up to 5 cm, not well appreciable. Method of Application of the Drug 4. Marked color change, in surrounding area up to 5 cm, well appreciable. The drug was applied externally as lepa. Required amount 5. Marked color change involving area >5cm. of the powder was mixed with sufficient quantity of water and applied as a coating over the affected area with even Swelling thickness. The lepa was washed once dried. This procedure was done twice daily with a gap of 12 h. 1. No swelling. 2. Slight edema, just at the point of bite, not well The application was over the lesion and surrounding area. appreciable. The first dose was on the first visit, irrespective of time. 3. Slight edema involving surrounding area. 4. Marked edema, involving surrounding area, well appreciable. Assessment Criteria 5. Marked pitting edema involving surrounding area.

It was tried best to grade the four cardinal symptoms such as Ruja, Kandu, Raga, and Shopha in the participants (Table 1). OBSERVATIONS AND RESULTS Apart from the above researches states that individually all the drugs of Shigrupunarnavadi lepa possess anti-inflammatory Among the 30 participants studied, males outnumbered the activity(Table 2).[9-17] females (73.3%), the majority of them were found in the age group of 31–40 years (53.3%). Almost three-fourths of the Pain participants were Hindus (73.3%). 60% of the participants 1. No pain. were agriculturists followed by students who constituted 10% 2. Pain only on pressure. of the study participants. 20% of the bite was in the upper arm,

Table 1: Effect of therapy on different signs and symptoms of Keeta Visha Symptoms Mean score % relief SD SE t P B.T A.T Ruja 2.82 0.66 76.59 0.86 0.20 10.68 0.001 Kandu 1.60 0.66 58.75 1.51 0.35 2.68 0.020 Raga 2.4 1.1 54.16 0.76 0.243 5.34 0.001 Shopha 2.32 0.44 81.03 0.96 0.22 8.54 0.001 SD: Standard deviation

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13.3% in the forearm, and 10% in the palm, thus constituting DISCUSSION a total of 43.33% on the upper limb, 6.6% of the bite was on the trunk. 10% of the bite was on the thigh, 6.66% in the Table 3 summarizes Guna and Karmas of ingredients of calf region, and 23.33% on the foot thus constituting a total Shigrupunarnavadi powder. of 46.66% in the lower limb. 10% of the bite was noted on the face and neck region. Out of the 30 participants, 16.66% came with single bite mark, 60% had two bite marks, whereas Vishaghna Property 23.33% had no bite marks. Maximum bites were seen in the intervals between 6 and 8 A.M and 5 and 7 P.M (43% and 37%, All the ingredients of this yoga possess vishaghna property. respectively). 30% of the total participants showed the features Hence, this combination may be administered in all conditions of Vataja keeta damsa, 50% of Pittaja, 10% of Kaphaja, and of visha. 10% showed the features of Sannipatajakeetadamsa. 10% of the total participants belonged to the Lootadamsha, 13.33% Doshahara Property to Vrischikadamsha, 6.66% to Kanabha, 6.66% to Makshika, 10% to Pipeelika, 6.66% to Mashaka, 10% to Shatapadi, and Shigru, Punarnava, Haridra, Vaca, Paata, Eswara Mooli are 36.66% were Anirdishyakeetadamsha. having kapha and vata hara property; Yashtimadhu is having vata and pitta hara property; shireesha is having pitta and Results vata hara property, and Gokshura is having vata pitta hara property. Visha vitiates all the dosha, so the combination of Ruja in the subjects showed an improvement of 76.59%, Kandu drugs, which is tridoshahara with property of vishaghnata, 58.75%, raga 54.16%, and shopha 81.03%, respectively. will be very efficacious in this condition.

Table 2: Chemical constituents and probable action of the ingredients of the trial drug Name of drug Chemical constituent Action Shigru Sterols, terpenes, moringine, pteregospermine Oedema suppression, anti‑inflammatory action Punarnava Hentriacontane, B‑sitosterol, punarnavine Possesses free radical scavenging effect thus reducing inflammation Haridra Curcumene, Curcumenone, B‑sitosterol Molecules involved in inflammation are inhibited by curcumin Vaca Acolamone, Aryl aldehydes, Acorin, Eugenol, Significant anti‑inflammatory activity Candana Santalol, santalenes, Anti‑inflammatory effect Paata Fangchinoline, cycleapeltine, cycleadrine, burmannaline Eswara Mooli Aristalochine, aristolochic acid cephaeradiones Anti‑inflammatory effect Yashti Glycyrrizine, Isoliquiritin, Liquiritin Anti‑inflammatory effect Shireesha Tannins, B‑sitosterol, Albigenin, saponins Anti‑inflammatory effect Gokshura Glycoside, Sterol, Tannin, and Harmine Anti‑inflammatory effect chlorogenin, diosgenin, gitogenin

Table 3: Rasa panchaka of ingredients of Sigrupunarnavaadi Choorna Name of drug Rasa Guna Veerya Vipaka Prabhava Shigru Katu, Tikta Lagu, Rooksha, Teekshna. Ushna Katu Vishahara Punarnava Madhura, Tikta, Kashaya Lagu, Rooksha Ushna Katu Haridra Tikta, Katu Lagu, Rooksha Ushna Katu Vishahara Vaca Tikta, Katu Lagu, Teekshna. Ushna Katu Candana Tikta, Madhura Lagu, Rooksha Sheeta Katu Vishahara Paata Tikta Lagu, Teekshna Ushna Katu Eswara Mooli Tikta, Katu Lagu, Teekshna Ushna Katu Vishahara Yashti Madhura Guru, Snigdha Sheeta Madhura Vishahara Shireesha Kashaya, Tikta Madhura Lagu, Rooksha, Teekshna Eeshatushna Katu Vishahara Gokshura Madhura Guru, Snigdha Sheeta Madhura

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S175 Bhat: Shigrupunarnavaadi lepa reduces the local reactions in Keeta visha

In inflammatory edema, pain is due to vata; redness, Publication; 2002. p. 521. temperature, and burning sensation, is due to pitta; edema, 5. Chakrapanidatta. Ayurveda Dipika, Commentary oozing, and itching; is due to kapha; and induration is due on Charaka Samhita. Chikitsasthana. 23/140. 5th ed. to vaatakapha. Hence, the above-said combination aptly acts New Delhi: Munshiram Manoharalal Publishers Pvt. on this clinical condition by virtue of its doshaghna property. Ltd.; 1992. p. 577. 6. Thampuran K. Prayoga Samucchayam. Kodungallur: Devi book Stall (Publishers); 1998. p. 76. Action by Virtue of Rasa-guna 7. Chakrapanidatta. Ayurveda Dipika, Commentary on Charaka Samhita. Sutrasthana. 26/43, 5th ed. New Delhi: Out of the ten drugs in the combination, eight drugs have Munshiram Manoharalal Publishers Pvt. Ltd.; 1992. tiktapradhana rasa. Tikta rasa acts as raktaprasadaka, p. 144. kandughna, and kushtaghnaanddaha prashamana.[7] By virtue 8. Chaukhambha Sanskrit Sansthan. Bhavamishra. of these karma based on the rasa, the drug could have reduced Bhaavprakaasha, I Vol. 6/202. Pandit Brahma Shankar itching, redness, and swelling. Mishra. 8th ed. Varanasi: Chaukhambha Sanskrit Sansthan; 2003. p. 276. By virtue of its gunas, the drug is laghu and 9. Rao KN, Gopalakrishnan V, Loganathan V, Nathan SS. rookshagunapradhana and also is kaphaghna.[8] Due to this, Anti-inflammatory activity of Moringa oliefera. Lam. shopha, which is Kaphaja, gets reduced. Anc Sci Life 1999;18:195-8. 10. Rachh PR, Rachh MR, Modi DC, Shah BN, Apart from the above researches states that individually all the Bhargava AS. In-vitro evaluation of antioxidant activity drugs of Shigrupunarnavadi lepa possess anti-inflammatory of Punarnava (Boerhaavia diffusa Linn.). Int J Pharm activity.[9-17] Res 2009;1:36-40. 11. Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). CONCLUSION J Altern Complementary Med 2003;9:161-8. 12. Shah PD, Ghag M, Deshmukh PB, Kulkarni Y, Joshi SV, Within the limits of the present study, it can be concluded Vyas BA, et al. Toxicity study of ethanolic extract of that Shigrupunarnavadi lepa helps to reduce the local Acorus calamus rhizome. Int J Green Pharm 2012;6:29. reactions including ruja, kandu, raga, and shophaand, 13. Gacche RN, Dhole NA. Antioxidant and possible anti- hence, can be recommended as external application in the inflammatory potential of selected medicinal plants management of keeta visha. prescribed in the Indian traditional system of medicine. Pharm Biol 2006;44:389-95. 14. Desai DC, Jacob J, Almeida A, Kshirsagar R, Manju SL. REFERENCES Isolation, structural elucidation and anti-inflammatory activity of astragalin, (-)hinokinin, aristolactam I and 1. Mehta VR. Cutaneous reactions to insect bites. Indian J aristolochic acids (I & II) from Aristolochia indica. Dermatol Venerol Leprol 1980;46:225-9. Nat Prod Res 2014;28:1413-7. 2. Chakrapanidatta. Ayurveda Dipika, Commentary 15. Anil K, Jyotsna D. Review on Glycyrrhiza glabra on Charaka Samhita. Chikitsasthana. 12/7, 5th ed. (Liquorice). J Pharm Sci Innov 2012;1:1-4. New Delhi: Munshiram Manoharalal Publishers Pvt. 16. Kajaria D, Tripathi JS, Tiwari SK, Pandey BL. The Ltd.; 1992. p. 483. analgesic and anti-inflammatory activities of the 3. Chaukhamba Orientalia Publication. Vagbhata, Ashtang hydroalcholic extract of “shirishadi compound” in Hridaya, Sarvaangasundara and Ayurveda Rasaayana, animal model. J Appl Pharm Sci 2011;1:98-101. Nidanasthana. 13/40, Collated by Anna Moreshwara 17. Baburao B, Rajyalakshmi G, Venkatesham A, Kunte. 9th ed. Varanasi: Chaukhamba Orientalia Kiranb G, Sunderb AS, Rao CB. Anti-inflammatory and Publication; 2002.p. 521. antimicrobial activities of methanolic extract of Tribulus 4. Chaukhamba Orientalia Publication. Vagbhata, Ashtang terrestris linn plant. Int J Chem Sci 2009;7:1867-72. Hridaya, Sarvaangasundara and Ayurveda Rasaayana, Nidanasthana. 13/42, Collated by Anna Moreshwara Kunte. 9th ed. Varanasi: Chaukhamba Orientalia Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S176 Review on antianxiety activity of some indigenous plants

Sonali Keshari1, Dev Nath Singh Gautam2, Narendra Kumar Singh1 1Pharmacy Ayurveda Research Laboratory, Rajiv Gandhi South Campus, Banaras Hindu University, Barkachha, Mirzapur – 231 001, Uttar Pradesh, India, 2Department of Rasa Shastra, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi – 221 005, Uttar Pradesh, India

Abstract

Anxiety is a public emotional phenomenon in humans characterized by uneasiness, discomfort, and concern or fear about some determined or indeterminate future warning. Anxiety is considered to be a usual reaction to stress

REVIEW ARTICLE REVIEW and involves heart palpitations, fatigue, nausea, and shortness of breath. In the current decade, anxiety is the most mutual mental illness affecting 1/8th of the total population and has become a very significant area of investigation in psychopharmacology. About 500 million individuals in the world suffer from anxiety disorder. The prevalence of anxiety disorders is 30.5% and 19.2% in women and men, respectively. The prevalence of anxiety disorders is remarkably high in young people. Children of age 7–11 years reported a 15.4% prevalence rate of anxiety disorders. A survey has also revealed that <14% of people with such psychiatric disorders receive treatment in any form. Current medications (selective serotonin reuptake inhibitor and tricyclic antidepressants) focus on the blockade of norepinephrine and serotonin uptake, thereby prolonging their synaptic effects. The relative success of these agents generates a conceptual impasse that limits identification of novel therapeutic targets for these disorders.[14] Several models (amphetamine-induced, pentylenetetrazole-induced, picrotoxin-induced, strychnine- induced, isoniazid-induced, yohimbine and footshock-induced anxiety, etc.) are used for the evaluation of antianxiety activity of different extracts as well as isolated compounds in rats. In the present manuscript, data on antianxiety activity of different extracts and isolated compounds from 39 indigenous plants were represented.

Key words: Anxiety, psychopharmacology, stress, tricyclic antidepressants

INTRODUCTION shortness of breath. In the current decade, anxiety is the most mutual mental illness affecting 1/8th of the total population tress and anxiety are psychiatric and has become a very significant area of investigation in manifestations of the modern world and psychopharmacology.[6] Slifestyles. However, too much stress, or a strong response to stress, is injurious Some unit of anxiety is a part of normal life and treatment to the health. It is responsible not only for is needed when it is disproportionate to the situation and poor health but also for specific physical or extreme. Approximately psychotics and depressed patients psychological sicknesses such as infections, also exhibit pathological anxiety.[7] Psychological anxiety and heart disease, and depression. Persistent and distress can be categorized as generalized anxiety disorder, unrelenting stress may lead to anxiety and social phobia, and post-traumatic stress disorder.[8] harmful behaviors. Psychiatric illnesses are major disorder of organic or emotional origin It is considered to be a normal reaction to stress or and always associated with severe distortion characterized as a state of being that arises from common and of thought, behavior, and capacity to recognize non-specific stimuli perceived as being potentially aggressive reality as well as deficient perception leading in the future. This perception often results in an apprehensive to delusion and hallucination and subsequent neurochemical imbalance in the brain.[1]Anxiety Address for correspondence: is a public emotional phenomenon in humans Dr. Narendra Kumar Singh, Pharmacy Ayurveda characterized by uneasiness, discomfort, and Research Laboratory, Rajiv Gandhi South concern or fear about some determined or Campus, Banaras Hindu University, Barkachha, indeterminate future warning.[2-5] Anxiety is Mirzapur – 231 001, Uttar Pradesh, India. considered to be a usual reaction to stress and E-mail: [email protected] involves heart palpitations, fatigue, nausea, and

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S177 Keshari, et al.: Indigenous plants for anxiety mood accompanied by increased arousal and vigilance, of the roots and rhizomes showed anxiolytic activity at 100– which when taken to an extreme persist for extended periods 300 mg/kg dose.[20] of time.[9] Atibala Several studies revealed that among the behavioral disorders, anxiety has the maximum frequency.[10] Anxiety has several Abutilon indicum L. commonly known as Atibala belongs mental and physical signs including palpitation, cramp, to the family Malvaceae. Alcoholic extract of leaves showed perspire, asthma, nausea, provocation, urination, failure to anxiolytic activity at 100–400 mg/kg doses.[21] encounter position, uncertainty about future, feeling of fear and stress, expectation of sorrow occurrence, inability of concentration, and night sleeplessness.[11] About 500 million Shirish individuals in the world suffer from anxiety disorder.[12] Anxiety disorders are psychiatric disorders affecting nearly Albizia lebbeck (L.) Benth. commonly known as Shirish 25% of the adult population at several stages of their life. belongs to family Mimosaceae. n-butanolic extract of dried The prevalence of anxiety disorders is 30.5% and 19.2% in leaves containing saponins showed anxiolytic and nootropic women and men, respectively. The prevalence of anxiety activity at the dose of 25 mg/kg dose.[22] disorders is remarkably high in young people. Children of age 7–11 years reported a 15.4% prevalence rate of anxiety Taalisa patra disorders. A survey has also revealed that <14% of people with such psychiatric disorders receive treatment in any Abies pindrow Royle is a large evergreen tree commonly [13] form. known as Taalisa belonging to family Pinaceae. Ethanolic extract of leaves showed anxiolytic effects at 50–100 mg/kg dose.[23] Chloroform and methanol extract of aerial parts HERBAL MEDICATIONS FOR ANXIETY exhibited significant antianxiety activity at 200–400 mg/kg dose, respectively. The ethyl acetate and n-butanol fractions Major limitation in the development of new antianxiety drugs of methanol extract showed anxiolytic activity at the dose of is a fundamental lack of a coherent pathophysiology and dose 50 mg/kg.[24] etiology for major depression, bipolar disorder, and common anxiety disorders. Current medications (selective serotonin reuptake inhibitor and tricyclic antidepressants) focus on Lahsune blockade of norepinephrine and serotonin uptake, thereby prolonging their synaptic effects. The relative success of these Allium ascalonicum Linn. is an annual herbaceous plant, agents generates a conceptual impasse that limits identification commonly known as Shallot, belongs to family Liliaceae. of novel therapeutic targets for these disorders.[14] Several The hydroalcoholic extract of aerial part showed anxiolytic [25] models (amphetamine-induce, pentylenetetrazole-induced, activity at the dose of 100 mg/kg. picrotoxin-induced, strychnine-induced, isoniazid-induced, yohimbine and footshock-induced anxiety, etc.) are used for Apamarga the evaluation of antianxiety activity of different extracts as well as isolated compounds in rats.[15] Achyranthes aspera Linn. commonly known as Apamarga belongs to the family Amaranthaceae. Methanol extract of fresh leaves showed anxiolytic activity at 100–600 mg/kg Ashwagandha dose.[26] Withania somnifera is commonly known as Ashwagandha, Indian ginseng, and winter cherry belongs to the family Neem Solanaceae.[16] Roots of W. somnifera showed anxiolytic activity at the dose of 20 and 50 mg/kg body weight due to Azadirachta indica commonly known as Neem belongs to the glycoside withanolides.[17] Chloroform and water fractions of family Meliaceae. Aqueous extract of fresh leaves of neem the hydroalcoholic extract of roots at the dose of 40 mg/kg showed anxiolytic activity at 10–200 mg/kg dose.[27] show anxiolytic activity.[18] Traditional extract (water: honey: ghee) of roots showed anxiolytic and antidepressant activity Kusmand at 250 mg/kg dose.[19] Benincasa hispida commonly known as Kushmanda belongs Yasthimadhu to the family Cucurbitaceae.[28] Methanolic extract of fresh fruits showed anxiolytic activity at the dose 300 mg/kg.[29] Glycyrrhiza glabra Linn. is commonly known as Yashtimadhu Alcoholic extract showed anxiolytic activity at 200 and belongs to the family Fabaceae. The hydroalcoholic extract 400 mg/kg dose.[30]

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Kasmard Dugdhika

Cassia occidentalis which is commonly called Kasmard Euphorbia hirta, an important medicinal herb, commonly belongs to the family Caesalpiniaceae. Ethanolic and known as Dugdhika, belongs to the family Euphorbiaceae. aqueous extracts of leaves show antianxiety activity at Hydroalcoholic extract of the whole plant showed anxiolytic 500 mg/kg, but an ethanol extract possesses more significant property at the dose of 200 mg/kg.[46] The lyophilized aqueous antianxiety and antidepressant activity compared to aqueous extract showed sedative and anxiolytic activity at 12.5 and [31] extract. 25 mg/kg dose.[47]

Dhanyak Kakodumber

Coriandrum sativum L. is an annual herb commonly known Ficus hispida Linn.is a moderate-sized tree commonly known as Dhanyak belongs to the family Umbelliferae. The aqueous as Kakodumber belongs to the family Moraceae.[48] Methanol extract of seeds at the dose of 200 mg/kg showed an anxiolytic extract of the leaf showed anxiolytic activity at the dose of effect.[32] Aqueous extract of leaf showed antianxiety activity 200–400 mg/kg.[49] at 50, 100, and 200 mg/kg dose.[33] Hydroalcoholic extract of fruits showed antianxiety activity at the doses of 100 and 200 mg/kg.[34] The aqueous extract of seed shows an anxiolytic Fennel activity at 50, 100, and 500 mg/kg.[35] The aqueous extract of seed shows an anxiolytic activity at 10–100 mg/kg.[36] Foeniculum vulgare Mill. commonly known as Fennel Hydroalcoholic extract of leaves showed anxiolytic effect at belongs to Apiaceae family. Ethanolic extract of fruits the dose of 200 and 400 mg/kg.[37] showed anxiolytic activity at 100–200 mg/kg dose.[50] The essential oil of F. vulgare showed anxiolytic activity at 100 [51] Kesar/saffron and 200 mg/kg doses.

Crocus sativus L. is a perennial herb, commonly known as Krishna Vasa Saffron, belongs to the family Iridaceae. Crocins, isolated compound from C. sativus L. showed anxiolytic activity at Justicia gendarussa Burm f. commonly known as Willow- [38] the dose of 50 mg/kg. The aqueous extracts of C. sativus leaved justicia belong to the family Acanthaceae. The ethanol contain active component safranal showed an anxiolytic extract of aerial parts possesses significant antianxiety [39] activity at the doses of 0.15 and 0.35 ml/kg body weight. activity at 200–500 mg/kg doses.[52] Acetonitrile extract of stigmas of the plant showed antianxiety activity at 60 mg/kg.[40] Rugmini

Talmuli Ixora coccinea Linn. a small-to-medium sized hardy shrub commonly known as West Indian jasmine belongs to Curculigo orchioides Gaertn. is commonly known as Kali family Rubiaceae. The ethanol extract of the whole plant at musali belongs to the family Amaryllidaceae. Methanol 400 mg/kg dose showed anxiolytic activity.[53] extract and aqueous extract of dried rhizome showed maximum anxiolytic activity at the dose 400 mg/kg.[41] Ikhwaku Paribhadra Lagenaria siceraria is commonly known as Bottle gourd [54] Erythrina variegata is a medium-sized deciduous small tree, belongs to the family Cucurbitaceae. Aqueous extract of [55] commonly known as Coral tree, belongs to family Fabaceae. fresh fruits showed anxiolytic activity at 200 mg/kg dose. The aqueous extract of stem bark at medium (200 mg/kg) and Methanol extract of L. siceraria at higher dose 400 mg/kg high (400 mg/kg) doses showed anxiolytic effect.[42] produced anxiolytic effect.[56]

Snuhi Amra

Euphorbia neriifolia Linn. is small erect, fleshy glabrous Mangifera indica commonly known as Mango belongs shrub commonly known as Snuhi belongs to the family to the family Anacardiaceae. Aqueous extract of leaves Euphorbiaceae.[43,44] Hydroalcoholic extract of leaves shows showed anxiolytic activity at 250 mg/kg and 500 mg/kg antianxiety effect at 400 mg/kg dose.[45] dose.[57]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S179 Keshari, et al.: Indigenous plants for anxiety

Shigru extract of leaves showed anxiolytic activity at 100 mg and 300 mg/kg doses.[75] Moringa oleifera commonly known as Drumstick tree belongs to the family Moringaceae.[58] Ethanol extract Karvellak of leaves showed anxiolytic property at 200 mg/kg and 400 mg/kg dose.[59-61] The plant Momordica charantia Linn. is a well-known plant and commonly known as Bitter gourds belong to family Jatiphala Cucurbitaceae.[76] Methanol extract of dry leaves showed anxiolytic activity at 100, 200, and 300 mg/kg doses.[77] Myristica fragrans an evergreen tree commonly known as Methanol extract of the whole plant showed anxiolytic Nutmeg belongs to family Myristicaceae. Ethanolic extract activity at 200 mg/kg dose.[78] of the whole plant at the doses of 25 mg/kg and 50 mg/kg possess anxiolytic activity.[62] Gorakhmundi

Kumud Sphaeranthus indicus Linn. is a highly branched herb commonly known as Gorakhmundi belongs to family Nymphaea alba is an aquatic, flowering, and rhizomatous Asteraceae. Hydroalcoholic extract of the whole herb herbs commonly known as White lotus or Water lily belongs to showed anxiolytic activity at 100 mg/kg.[79] Petroleum ether, the family Nymphaeaceae. Ethanol extract of the whole plant alcohol, and aqueous extract of flowers showed anxiolytic showed anxiolytic activity at 100 and 200 mg/kg doses.[63] activity at the dose of 10 mg/kg, 10 mg/kg, and 30 mg/kg, respectively.[80] Changeri Haritaki Oxalis corniculata Linn. is somewhat delicate appearing, low growing, herb, commonly known as Creeper wood sorrel, Terminalia chebula is a medium-to-large-sized tree commonly belongs to the family Oxalidaceae.[64-67] Ethanol extract of the known as Haritaki belongs to family Combretaceae. Aqueous whole plant at 100 and 300 mg/kg showed anxiolytic activity.[68] extract of fruits shows anxiolytic activity at the dose of 1.3 and 2.6 mg/kg.[81] Aqueous extract of fruits shows anxiolytic activity at the dose of 18mg/kg.[82] Hydroalcoholic extract of Passion flower dry fruits which contains active component chebulinic acid showed anxiolytic activity at 20 mg/kg and 40 mg/kg.[83] Passiflora incarnate is commonly known as Passion flower belongs to family Passifloraceae. Aqueous fraction of methanol extract of leaves showed anxiolytic effect at 30 mg/ Nirgundi kg dose.[69] Methanol extract of P. incarnate showed anxiolytic activity at 200 mg/kg dose.[70] Ethanol extract of P. incarnate Vitex negundo Linn. is a large aromatic shrub, commonly showed anxiolytic activity at 375 mg/kg doses.[71] Butanol known as Nirgundi, belongs to the family Verbenaceae. fraction of a hydroalcoholic extract of aerial parts at the dose Chloroform and ethanol extract of the roots showed anxiolytic of 2.1 mg/kg and 4.2 mg/kg and chloroform fraction in doses activity at 400 mg/kg and 100 mg/kg doses, respectively.[84] of 0.17 mg/kg and 0.34 mg/kg both correspond to a total An ethanol extract of roots of V. negundo showed anxiolytic extract at the dose of 150 and 300 mg/kg showed anxiolytic activity at 100 and 200 mg/kg.[85] Ethanol extract of leaves activity.[72] showed anxiolytic activity at 200, 300 mg/kg doses.[86]

Kava kava Vacha

Piper methysticum is a perennial plant commonly known Acorus calamus Linn. is commonly called as Sweet flag as Kava belongs to Piperaceae family. Ethanol extract of belongs to the family Araceae. Hydroalcoholic extract of kava roots showed anxiolytic activity at 125 mg/kg and rhizome showed anxiolytic activity at 500 mg capsule twice 88 mg/kg doses.[73] Extract of roots showed anxiolytic activity daily for 60 days.[87] at 120‑240 mg/kg doses.[74] Brahmi Lemon balm Bacopa monnieri (L.) Wettst. is commonly known as Brahmi Melissa officinalis L., commonly known as Lemon balm, is belongs to the family Scrophulariaceae. Whole plant extracts a perennial shrub belongs to the family Lamiaceae. Ethanol showed anxiolytic effects at 10 and 20 mg/kg doses.[88]

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Methanol extract of the whole plant showed anxiolytic 2. Kjernisted KD, Bleau P. Long-term goals in the activity at 10, 20, or 30 mg/kg doses.[89] management of acute and chronic anxiety disorders. Can J Psychiatry 2004;49:51S-63S. 3. Weinberger DR. Anxiety at the frontier of molecular Bhanga medicine. N Engl J Med 2001;344:1247-9. 4. Clément Y, Calatayud F, Belzung C. Genetic basis of Cannabis sativa is commonly known as Bhanga belongs to anxiety-like behaviour: A critical review. Brain Res Bull the family Cannabaceae. Cannabidiol isolated from C. sativa 2002;57:57-71. showed anxiolytic effect at 2.5–10 mg/kg doses.[90] Cannabidiol 5. Gupta V, Bansal P, Kumar S, Sannd R, Rao MM. showed anxiolytic effect at 300 mg dose in human.[91] Therapeutic efficacy of phytochemicals as anti-anxiety-a review. J Pharm Res 2010;3:174-9. Mandukparni 6. Jung JW, Yoon BH, Oh HR, Ahn JH, Kim SY, Park SY, et al. Anxiolytic-like effects of gastrodia elata and Centella asiatica (Linn.) is an herbaceous plant, commonly its phenolic constituents in mice. Biol Pharm Bull known as Mandukparni, belongs to the family Apiaceae. 2006;29:261-5. Hexane, ethyl acetate, and methanol extracts of the whole 7. Tripathi KD. Essentials of Medical Pharmacology. 6th ed. plant showed anxiolytic activity at 3, 5, and 10 mg/kg New Delhi: Jitendar P VijJaypee Brothers Medical doses.[92] Extract of the whole plant showed anxiolytic Publishers (P) Ltd.; 2007. activity at the 500 mg/kg dose.[93] 8. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 4th ‘Text Revision’ ed. Washington, DC: American Psychiatric Shunthi Association; 1994. Zingiber officinale Roscoe., commonly known as Adraka, 9. Dias BG, Banerjee SB, Goodman JV, Ressler KJ. belongs to the family Zingiberaceae. Benzene fraction of Towards new approaches to disorders of fear and anxiety. petroleum ether extract of dried rhizomes showed anxiolytic Curr Opin Neurobiol 2013;23:346-52. activity at 100 and 200 mg/kg doses.[94] Ethanol and aqueous 10. Farahani MF. Descriptive Dictionary of Educational extracts of the rhizomes showed anxiolytic activity at 200 Science. Tehran: Asrar-e Danesh Press; 1999. and 400 mg/kg doses.[95] 11. Borkovec TD, Lyonfields JD. Worry: Thought suppression of emotional processing. In: Krohome HW, editor. Attention and Avoidance: Strategies in Coping Agatsya with Aversiveness. Seattle: Hogrefe & Huber Publishers; 1993. p. 101-8. Sesbania grandiflora (L.) Poiret., is commonly known as 12. Kaviani H, Mousavi AS. Psychometric properties of the Agatsya, belongs to Fabaceae family. Benzene:ethylacetate Persian version of beck anxiety inventory (BAI). Tehran fraction of acetone soluble part of a petroleum ether extract Univ Med J 2008;66:136-40. [96] of leaves showed anxiolytic activity at 100 mg/kg dose. 13. Leon AC, Portera L, Weissman MM. The social costs of anxiety disorders. Br J Psychiatry Suppl 1995;27:19-22. 14. Healy D. The dilemmas posed by new fashionable CONCLUSION treatments. Adv Psychiatr Treat 2001;7:322-7. 15. Vogel HG. Drug Discovery and Evaluation: The use of natural products is as ancient as human civilization Pharmacological Assays. 2nd ed. Springer – New York: and for a long time, plants were the main sources of drugs Verlag Berlin Heidelberg 2002. p. 401-58. for their therapeutic nature. According to the World Health 16. Singh RH, Udupa KN. Clinical and experimental Organization, plant-based medicine is still the mainstay of studies on rasayana drugs and rasayana therapy. Special about 80% of the population in the developing countries, hence Research Monograph, Central Council for Research in extensive investigation is very much needed to standardize Ayurveda and Siddha (CCRAS). New Delhi: Ministry of and validate the accrued knowledge of traditional medicine. Health and Family Welfare; 1993. Synthetic drugs used for the treatment of various diseases are 17. Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. not free from side effects. In the coming future, it is necessary Anxiolytic-antidepressant activity of Withania to develop the potential candidates from the plants for the somnifera glycowithanolides: An experimental study. treatment of various psychopharmacological disorders. Phytomedicine 2000;7:463-9. 18. Khan ZA, Ghosh AR. L-Arginine abolishes the anxiolytic‑like effect of withaferin-a in the elevated REFERENCES plus‑maze test in rats. Afr J Pharm Pharmacol 2011;5:234-7. 1. Barar FS. Essentials of Pharmacotherapeutics. 19. Ramanathan M, Srinivasan J, Saravanbabu C, New Delhi: S Chand Publication; 2006. Viswanad B, Suresh B. Comparative behavioral

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51. Mesfin M, Asres K, Shibeshi W. Evaluation of anxiolytic 66. Kathiriya AK, Das K, Joshipura M, Mandal N. Oxalis activity of the essential oil of the aerial part of Foeniculum corniculata Linn. The plant of Indian subtropics. Herb vulgare miller in mice. BMC Complement Altern Med Tech Ind 2010;1:7-11. 2014;14:310. 67. Madhava KS, Sivaji K, Tulasi RK. Flowering plants 52. Subramanian N, Jothimanivannan C, Senthil KR, of Chitoor District, Andhra Pradesh, India. Tirupati: Kameshwaran S. Evaluation of anti- anxiety activity of Student Offsent Printers; 2008. p. 54. Justicia gendarussa Burm. Pharmacologia 2013;4:404-7. 68. Gupta G, Kazmi I, Afzal M, Rahman M, Anwar F. 53. Mohammed SP, Latheef N, Ganeshan PS. Evaluation Anxiolytic effect of Oxalis corniculata (Oxalidaceae) in of anxiolytic activity of Ixora coccinea Linn. Ethanolic mice. Asian Pac J Trop Dis 2012;2012:S837-40. extract in swiss albino mice. Clin Exp Pharmacol 69. Santos KC, Kurtz SM, Müller SD, Biavatti MW, 2014;4:146. Oliveira RM, Santos CA. Sedative and anxiolytic effects 54. Rahman AS. Bottle gourd (Lagenaria siceraria)-a of methanolic extract from the leaves of Passiflora vegetable for good health. Nat Prod Radiance actinia. Braz Arch Biol Technol 2006;49:565-73. 2003;2:249-50. 70. Brown E, Hurd NS, McCall S, Ceremuga TE. Evaluation 55. Aslam M, Najam R. Anxiolytic and memory enhancing of the anxiolytic effects of chrysin: A Passiflora activity of Lagenaria siceraria in rodents. Int J Biomed incarnate extract, in the laboratory rat. Am Assoc Nurse Adv Res 2013;4:40-6. Anesth 2007;75:333-7. 56. Prajapati R, Kalariya M, Parmar S, Sheth N. Anxiolytic 71. Grundmann O, Wähling C, Staiger C, Butterweck V. effects of Lagenaria siceraria fruits on the elevated plus Anxiolytic effects of a passion flower (Passiflora maze model of anxiety in rats. Asian J Ethnopharmacol incarnata L.) extract in the elevated plus maze in mice. Med Foods 2016;2:2630. Pharmazie 2009;64:63-4. 57. Patel NB, Kumar S, Prasad AK, Patel JA, Patel HA. 72. Sampath C, Holbik M, Krenn L, Butterweck V. Assessment of anxiolytic activity of aqueous extract of Anxiolyticeffects of fractions obtained from Passiflora Mangifera indica L. Leaves in rodents exposed to chronic incarnate L. In the elevated plus maze in mice. Phytother unpredictable mild stress. Int Res J Pharm2013;4:247-51. Res 2011;25:789-95. 58. Ganatra TH, Joshi UH, Bhalodia PN, Desai TR, 73. Garrett KM, Basmadjian G, Khan IA, Schaneberg BT, Tirgar PR. A panoramic view on pharmacognostic, Seale TW. Extracts of kava (Piper methysticum) induce pharmacological, nutritional, therapeutic and acute anxiolytic-like behavioral changes in mice. prophylactic values of Moringa oleifera Lam. Int Res J Psychopharmacology (Berl) 2003;170:33-41. Pharm 2012;3:1-7. 74. Rex A, Morgenstern E, Fink H. Anxiolytic-like effects of 59. Bhat SK, Joy AE. Antianxiety effect of ofethanolic kava-kava in the elevated plus maze test – a comparison extract of leaves of Moringa oleifera in Swiss albino with diazepam. Prog Neuropsychopharmacol Biol mice. Arch Med Health Sci 2014;2:5-7. Psychiatry 2002;26:855-60. 60. Lakshmi BV, Sudhakar M, Ramya RL. Anti-anxiety 75. Taiwo AE, Leite FB, Lucena GM, Barros M, Silveira D, activity of Moringa olieferaa seeds using different Silva MV, et al. Anxiolytic and antidepressant-like experimental anxiety models in mice. J Pharm Res effects of Melissa officinalis (lemon balm) extract in 2014;8:343-8. rats: Influence of administration and gender. Indian J 61. Bhattacharya A, Santra S, Mahapatra S, Sahu PK, Pharmacol 2012;44:189-92. Agrwal D, Kumar S. Study of anxiolytic effect of 76. Satyawati GV, Gupta AK, Tandan N. Medicinal plants of ethanolic extract of drumstick tree leaves on albino India. New Delhi: Indian Council of Medical Research; mice in a basic neuropharmacology laboratory of 1987. a postgraduate teaching institute. J Health Res Rev 77. Ganesan A, Natesan S, Vellayutham R, Manickam K, 2016;3:41-7. Ramasamy N. Anxiolytic, antidepressant and anti- 62. Nagaraju B, Sahar SH, Bolouri A, Kushnoor NZ, inflammatory activity of methanol extract of leaves of Zahra A, Zothanmawia C, et al. Anxiolytic effect of Momordica charantia Linn. (Cucurbitaceae). Iran J Myristica fragrans. Int J Phytother Res 2013;3:1-7. Pharmacol Ther 2008;7:43-7. 63. Thippeswamy BS, Mishra B, Veerapur VP, Gupta G. 78. Ishola IO, Akinyede AA, Sholarin AM. Antidepressant Anxiolytic activity of Nymphaea alba linn. In mice as and anxiolytic properties of the methanolic extract of experimental models of anxiety. Indian J Pharmacol Momordica charantia Linn. (Cucurbitaceae) and its 2011;43:50-5. mechanism of action. Drug Res (Stuttg) 2014;64:368-76. 64. Badwaik H, Singh MK, Thakur D, Giri KT, Tripathi DK. 79. Galani VJ, Patel BG. Effect of hydroalcoholic extract of The botany, chemistry, pharmacological and therapeutic Sphaeranthus indicus against experimentally induced application of Oxalis corniculata Linn. Int J Phytomed anxiety, depression and convulsions in rodents. Int J 2011;3:1-8. Ayurveda Res 2010;1:87-92. 65. Dreyer LL, Esler KJ, Zietsman J. Flowering phenology 80. Ambavade SD, Mhetre NA, Tate VD, Bodhankar SL. of South African Oxalis-Possible indicator of climate Pharmacological evaluation of the extracts of change. S Afr J Bot 2006;72:150-6. Sphaeranthus indicus flowers on anxiolytic activity in

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mice. Indian J Pharmacol 2006;38:254-59. Effect of acute and sub chronic use of Bacopa monnieri 81. Chandrashekar R, Manohar VR, Rao SN. Acute anxiolytic on dopamine and serotonin turnover in mice whole brain. effect of aqueous extract of fruits of Terminalia chebula Afr J Pharm Pharmacol 2012;6:2767-74. (AETC) in mice. Int J Pharm Bio Sci 2012;3:673-7. 90. Filho NG, Tufik S. Comparative effects between 82. Chandrashekar R, Manohar VR, Rao SN. Chronic cannabidiol and diazepam on neophobia, food intake and anxiolytic effect of aqueous extract of Terminalia chebula conflict behavior. Res Comm Psychol Psychiatr Behav (AETC) in rats. Drug Invent Today 2012;4:447-9. 1981;6:25-6. 83. Onasanwo SA, Faborode SO, Agrawal M, Ijiwola OL, 91. Zuardi AW, Cosme RA, Graeff FG, Guimarães FS. Jaiyesimi BO, Narender T. Antidepressant and anxiolytic Effects of ipsapirone and cannabidiol on human potentials of chebulinic acid in laboratory rodent. Ann experimental anxiety. J Psychopharmacol 1993;7:82-8. Depress Anxiety 2014;1:1032. 92. Chen SW, Wang WJ, Li WJ, Wang R, Li YL, Huang YN, 84. Sharma A, Gulsheen, Kumar A, Sharma A. Comparative et al. Anxiolytic-like effect of asiaticoside in mice. anti-anxiety potential of different parts of Vitex negundo Pharmacol Biochem Behav 2006;85:339-44. linn. Int J Pharma Sci Res 2018;9:282-5. 93. Wijeweera P, Arnason JT, Koszycki D, Merali Z. 85. Adnaik RS, Pai PT, Sapakal VD, Naikwade NS, Evaluation of anxiolytic properties of Gotukola— Magdum CS. Anxiolytic activity of Vitex negundo Linn. (Centellaasiatica) extracts and asiaticoside in rat Int J Green Pharm 2009;3:243-7. behavioral models. Phytomedicine 2006;13:668-76. 86. Aswar MK, Bidkar AA, Gujar KN, Athawale TG. 94. Vishwakarma SL, Pal SC, Kasture VS, Kasture SB. Anxiolytic like effects of leaves extract of Vitex negundo Anxiolytic and antiemetic activity of Zingiber officinale. (L) (fam:-verbaceae) in elevated plus maze test. J Nat Phytother Res 2002;16:621-6. Remedies 2012;12:141-50. 95. Harsha SN, Anilakumar KR. Anxiolytic effects of the 87. Bhattacharya D, Sur TK, Lyle N, Jana U, Debnath PK. extracts of Zingiber officinale in mice. J Pharm Res A clinical study on the management of generalized 2012;5:219-23. anxiety disorder with Vaca (Acorus calamus). Indian J 96. Kasture VS, Deshmukh VK, Chopde CT. Anxiolytic and Trad Know 2011;10:668-71. anticonvulsive activity of Sesbania grandiflora leaves in 88. Bhattacharya SK, Ghosal S. Anxiolytic activity experimental animals. Phytother Res 2002;16:455-60. of a standardized extract of Bacopa monniera: An experimental study. Phytomedicine 1998;5:77-82. 89. Rauf K, Subhan F, Abbas M, ulHaq I, Ali G, Ayaz M. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S184 A phytopharmacological review on Ludwigia octovalvis

Stuti Pandey1, Alakh N. Sahu2, Manmath K. Nandi1 1Department of Medicinal Chemistry, Faculty of Ayurveda, Institute of Medical Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India, 2Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, India

Abstract

Medicinal plants are used for the treatment and prevention of various diseases from ancient time due to their medicinal activities. The demand of traditional system of medicines is increasing day to day due to population

REVIEW ARTICLE REVIEW explosion, restricted supply and more side effects of synthetic drugs, and development of resistance to antibiotic used for contagious diseases. Recently, phytomolecules isolated from medicinal plants such as taxol, vincristine, morphine and quinine are getting preference for the treatment of diseases over synthetic drugs due to their fewer side effects. One of the Indian medicinal plants Ludwigia octovalvis (Onagraceae) is used traditionally for the treatment of various diseases such as edema, nephritis, hypotension, antimalarial, dysentery, diarrhea, diabetes, headache, fever, and toxemia, as carminative, laxative, vermifuge, astringent, and anthelminthic in nervous disorders and as analgesic in rheumatic pain and for swollen glands. Preliminary phytochemical study of the various extracts of Ludwigia octovalvis reported that the plant is rich with phenolics, alkaloids, steroids, glycosides and flavonoid compounds. Some phytomolecules such as beta-sitosterol, oleanolic acid, ursolic acid, oleanane-type triterpenes, daucosterol, luteolin, quercetin, and apigenin are isolated. Pharmacological activities such as hypoglycemic, antimicrobial, antioxidant, and anti-inflammatory activity are also investigated on this plant. This study compiles the information related to L. octovalvis, which will help the researchers for further study on this plant.

Key words: Antioxidants, flavonoids, Ludwigia octovalvis, triterpenes

INTRODUCTION diseases from phytomolecules isolated from medicinal plants such as taxol, vincristine, morphine, and quinine for the edicinal plants are used for the treatment of diseases over synthetic drugs due to their fewer treatment and prevention of various side effects.[5] India has a good diversity of medicinal plants, diseases from ancient time due to and near about 7800 pharmaceutical companies in India M involved in the manufacturing of formulation containing their medicinal activities. Plants rich with various phytochemicals and are used as whole medicinal plants or its parts and consumes about 2000 tons or its parts in both traditional and modern of plants in every year.[6] The traditional system of medicines medicines for the treatment or management of has a hopeful future as the world rich with millions of plants, various chronic diseases.[1] Traditional systems and most of them have some medicinal values, some are of medicines are widely adapted on many investigated and some are yet to be studied. One of the Indian countries, and 80% of the world population of medicinal plants Ludwigia octovalvis is used traditionally the developing countries depends on traditional for the treatment of various diseases, some pharmacological medicines for their primary health care.[2] In effects are investigated, and some are yet to be studied. The developed country like the United States of present review is designed to highlight the traditional use, America, about 38% of adults and 12% of pharmacognostical, phytochemical, and pharmacological children population are also prefer medicines studies carried out on L. octovalvis so that other possible designed from medicinal plants for their primary pharmacological activities could be investigated. health problems.[3] Recently, the demand of traditional system of medicines increased due to population explosion, restricted supply and more Address for correspondence: side effects of synthetic drugs, and development Dr. Manmath K. Nandi, Department of Medicinal of resistance to antibiotic used for contagious Chemistry, Faculty of Ayurveda, Institute of Medical diseases.[4] Pharmaceutical companies are now Science, Banaras Hindu University, Varanasi, designing new formulation for the treatment of Uttar Pradesh, India. E-mail: [email protected].

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S185 Pandey, et al.: A phytopharmacological review on Ludwigia octovalvis

PLANT PROFILE[7] leaf has upper and lower epidermis, cuticle, parenchyma, palisade ratio, vascular bundle, spongy parenchyma, and Kingdom: Plantae lignified xylem, whereas the transverse section study of its Division: Tracheophyta stem has epidermal layer, cork, vascular bundle, protoxylem, Class: Magnoliopsida metaxylem, and pith. Further, quantitative microscopical Order: Myrtales study of leaf and physicochemical study of J. suffruticosa has Family: Onagraceae been performed, and the parameters are reported as stomata Genus: Ludwigia index - 17.94, vein islet number - 23, vein termination Species: Octovalvis number - 16, palisade ratio - 56, moisture content - 8.9%, total ash value - 4.8%, acid-insoluble ash value - 1.3%, water- soluble ash value - 2.8%, and extractive value in alcohol and water - 8.0% and 8.8%, respectively.[16]

PHYTOCHEMICAL REVIEW

Biological activity shown by the plant extract is due to the presence of primary and secondary metabolite, and phytochemical screenings are performed to ascertain the primary and secondary metabolite present in the extract of the crude drugs. Kumar and Kashyap studied the extract of L. octovalvis and revealed that the alcoholic extract of whole plant part of L. octovalvis is rich with phenols, alkaloids, steroids, glycosides, and flavonoids.[16] Further, Mandal and Rath also studied separately the aqueous extract of leaf of 13 ethnomedicinal plants of Chilika lagoon including L. octovalvis and the study revealed that the plant extract is rich with flavonoids, alkaloids, DESCRIPTION phenols, tannin, saponin, and steroids but lack of glycosides.[17]

L. octovalvis (Synonyms: Oenothera octovalvis and Jussiaea Yakob et al. studied the leaf, stem, and root of L. octovalvis suffruticosa) belongs to family Onagraceae. The family extracted in 80% methanol, ethyl acetate, chloroform, and Onagraceae comprises 17 genera and 650 species,[8] which hexane for the total phenolic content. It has been reported that have potential bioactive compounds and used in traditional 80% methanolic extract of leaf and stem is rich in the total folk medicines. It is commonly known as Mexican primrose phenolic content as 264.76 ± 0.23 gallic acid equivalent (GAE) - willow (local name - Hiran khuri or bhulabang). It is mostly mg/g dry weight and 239.05 ± 0.29 GAE mg/g dry weight, grown in the moist area and native to India, Australia, China, respectively, whereas other extracts have comparatively low and Tropical America.[9] It is a perennial herb, which grown amount of total phenolic content.[18] Quantitative estimation of up to a maximum height of 4 m. The plant has erect, grooved, total phenolics and flavonoids content were also studied for and woody stem. Leaves are elongated with small hairs on the aqueous extract of leaves of Ludwigia octovalvis, and the both sides. Flowers are yellow in color with four petals and study reported that the total phenolic content in the extract was sepals and eight stamens. Fruits are ribbed capsule type with determined as 170 mg of GAE/g dry weight of extract and total very small seeds.[10] flavonoids content was determined as 147.102 mg CE (catechin equivalent)/g dry weight of extract.[17] The plant is used traditionally for the treatment of diseases like edema, nephritis, hypotension,[11] antimalarial, Yan and Yang isolated 13 phytomolecules from the medicinal dysentery, diarrhea, diabetes,[12] fever, toxemia, body ache,[13] plant L. octovalvis, and these were characterized from their carminative, laxative, vermifuge, astringent, antihelmintic,[14] spectroscopic data as beta-sitosterol, oleanolic acid, 2 alpha- nervous disorders, rheumatic pain and swollen glands.[15] hydroxy ursolic acid, tormentic acid, daucosterol, maltol, luteolin, quercetin, apigenin, methyl brevifolincarboxylate, gallic acid, 3, 4, 8, 9, 10-pentahydroxydibenzo[b, d]pyran-6- PHARMACOGNOSTICAL REVIEW one, and ellagic acid.[19]

The World Health Organization recommends to study specific Chang and Kuo also studied extract of L. octovalvis, and it physicochemical and pharmacognostical parameters for the has been reported that four compounds were isolated from identification and standardization of crude drugs of natural the ethyl acetate fraction of methanolic extract of whole plant origin. Kumar and Kashyap studied the transverse section as (23Z)-feruloylhederagenin, (23E)-feruloylhederagenin, of the leaf and stem of J. suffruticosa and reported that the β-amyrin acetate, and β-amyrin palmitate.[20]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S186 Pandey, et al.: A phytopharmacological review on Ludwigia octovalvis

In another study, Chang et al also isolated five compounds in balb/c mice infected with Shiga toxin of Escherichia ([23Z]-coumaroylhederagenin, [23E]-coumaroylhederagenin, coli strain 0157: H7. The study reported that after 14 days [3Z]-coumaroylhederagenin, oleanolic acid, and ursolic acid) treatment of extract, the level of serum IgA antibodies from the extract of the whole plant of L. octovalvis.[21] increased, whereas the level of serum IgG and IgM antibodies was not altered. It indicated that the immune- Structure of the some phytomolecules isolated from Ludwigia stimulating properties of 80% methanolic extract of L. octovalvis is given below: octovalvis against Shiga toxin-producing E. coli O157:H7 in Balb/c mice potentiated through increased level of serum IgA antibodies.[12]

DIURETIC ACTIVITY

Further, Murugesan et al. reported that methanolic extract of aerial part of J. suffruticosa showed dose-dependent diuretic activity in Wistar rats. This study has been performed on the basis of measurement of the volume of urine excreted and quantitative estimation of sodium, potassium, and chloride ions in the excreted urine after administration of a methanolic extract of J. suffruticosa at 200 and 400 mg/kg body weight. This study suggested that the plant could be an effective hypernatremic, hyperchloremic, and hyperkalemic diuretic drug.[14]

ANTIOXIDANT AND ANTIBACTERIAL ACTIVITY

Yakob et al. studied the 12 extracts of leaf, stem, and root PHARMACOLOGY REVIEW of L. octovalvis, extracted in 80% methanol, ethyl acetate, chloroform, and hexane to determine the total phenolic Antiaging effect content and antioxidant activity by in vitro method. The ferric-reducing antioxidant power (FRAP) activity and 2, Lin et al. revealed that extract of L. octovalvis significantly 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity increased the lifespan of both male and female Drosophila were determined using the extract by spectrophotometer melanogaster, when feeded with high calorie diet but method at 593 nm, and trolox was used as antioxidant in the extract was not effective with low-calorie diet. The both the methods as standard. It has been reported that 80% extract blocked the age-related cognitive damage in both methanolic extract of leaf showed maximum antioxidant male and female flies and in SAMP8 mouse. This study activity and the DPPH value and FRAP value for 80% also reported that extension of lifespan in flies may be methanolic extract of leaf were 1080.84 ± 6.07 µM trolox due to high rich in polyphenols and flavonoids content in equivalent (TE)/mg dry weight and 1256.88 ± 5.38 µM TE/mg the extract of L. octovalvis. It has been reported that gas dry weight. It showed that, with decrease in polarity of solvent, chromatography–mass spectrometry study of the extract the in vitro antioxidant activity decreases with the exception of L. octovalvis showed the presence of 17 bioactive that the ethyl acetate extract of root had highest antioxidant phytomolecules with the amount of β-sitosterol and value.[18] squalene was maximum. Further reported that β-sitosterol extended the lifespan of adult flies through AMP- In this study, they reported that 12 extracts of the plant were activated protein kinase and would be helpful in treating evaluated for antibacterial activity against Bacillus cereus age-related disorders.[11] (ATCC 10876), Bacillus licheniformis (ATCC 12759), Bacillus spizizenii (ATCC 6633), Staphylococcus aureus (ATCC 12600), Staphylococcus epidermidis (ATCC 12228), IMMUNE-STIMULATING PROPERTIES Streptococcus mutans (ATCC 25175), E. coli (ATCC 25922), Klebsiella pneumoniae (ATCC 13883), Pseudomonas In this study, Yakob et al. experimentally evaluated that 80% aeruginosa (ATCC 27853), Pseudomonas stutzeri (ATCC methanolic extract of L. octovalvis at a dose of 200 mg and 17588), and Shigella boydii (ATCC 9207) by disc diffusion 400 mg/kg enhances the immunity stimulating properties method and broth microdilution method. The study showed

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S187 Pandey, et al.: A phytopharmacological review on Ludwigia octovalvis that 80% methanolic extract of leaf is most effective against activity were 80 µg/ml, 125 µg/ml, 60 µg/ml, and 70 µg/ml, E. coli and B. spizizenii, while 80% methanolic root extract respectively. This study indicated that the aqueous extract of most effective against P. aeruginosa at minimum inhibitory leaf has good antioxidant activity.[17] concentration (MIC) and minimum bactericidal concentration value 62.5 µg/ml and 125 µg/ml.[18] TOXIC EFFECT In another study, Chen et al. evaluated the antibacterial activity of aqueous extracts of 79 medicinal plants against Yakob et al. studied 80% methanolic leaves extract of cariogenic bacterium, S. mutans. It has been reported that L. octovalvis and evaluated both acute and subacute toxic aqueous extract of L. octovalvis showed highest antibacterial effect on mice. In this acute toxicity study, the leave extract at activity along with Morus australis and Thuja orientalis, and a dose of 2000 mg/kg body weight was administered to mice the MIC value for the antibacterial activity was less than or for 14 days, and for sub-acute toxicity study, 200, 400, and [22] equal to 2.5–7.8 mg/ml. 800 mg/kg of extract were administered to mice for 28 days. This acute and subacute study revealed that 80% methanolic leaf extract of L. octovalvis did not cause any lethality and GLYCEMIC CONTROL AND MEMORY toxicological effects on mice.[25] PERFORMANCE ACTIVITY

Lin et al. studied the effect of L. octovalvis extract and ANTIDIABETIC STUDY β-sitosterol (isolated from it) for hypoglycemic activity in C2C12 muscle cells and in HepG2 hepatocellular cells (in Murugesan et al. evaluated the hypoglycemic and vitro model). This study reported that both L. octovalvis antihyperglycemic activity of methanolic extract of extract and β-sitosterol significantly induced AMPK J. suffruticosa in normal and alloxan-induced diabetic rats. phosphorylation and L. octovalvis extract also inhibited In this study, it has been reported that the extract at a dose glucose production and enhanced uptake of a fluorescent of 200 mg/kg and 400 mg/kg body weight significantly glucose derivative (2-NBDG). Lin et al. also studied the reduced plasma glucose level after oral administration and effect of L. octovalvis extract, β-sitosterol, and metformin in only the extract at a dose of 400 mg/kg reduces showed streptozotocin-induced diabetic mice, and it has been reported hypoglycemic activity in the alloxan-induced diabetic that both induce antihypoglycemic effect like metformin. rats.[26] Further, it has been reported that L. octovalvis extract also improves memory performance and attenuates glucose level in HFD feeding mice.[23] ANTIPYRETIC ACTIVITY

Murugesan et al. evaluated the methanolic extract of aerial ANTIOXIDANT ACTIVITY part of J. suffruticosa for antipyretic activity in normal and yeast-induced pyrexia in rats. The study reported that all the Shyur et al. studied the antioxidant activity and DNA dosages of extract (100, 200, and 300 mg/kg of body weight) protecting activity with extracts of 26 medicinal plants by showed a significant reduction in body temperature both in DPPH and superoxide anion scavenging activity in vitro normal and yeast-induced pyrexia in rats, and the effect was method. The study has been reported that of 26 medicinal maintained up to 5 h after administration in a dose-dependent plants, L. octovalvis most significantly inhibits free radical manner.[27] and superoxide anion and also protected the DNA damage by hydroxyl radicals. The study reported that IC50 value for

L. octovalvis was lowest among 26 plants. The IC50 values for free radical (DPPH) scavenging activity and superoxide CENTRAL NERVOUS SYSTEM (CNS) anion scavenging activity were 4.6 µg/ml and 25.9 µg/ml, ACTIVITY respectively.[24] Murugesan et al. also evaluated the methanolic extract of Mandal and Rath also evaluated the antioxidant activity the whole part of J. suffruticosa for CNS activity in rats of aqueous leaf extract of L. octovalvis by various in vitro and mice. In this study, the extract was evaluated at doses methods as DPPH scavenging activity, superoxide radical of 200 mg/kg and 400 mg/kg body weight for general scavenging activity, hydroxyl ion (OH) radicals scavenging behavior, exploratory behavior, muscle relaxation activity, activity, and nitric oxide (NO) scavenging activity methods. and sleeping time induced by phenobarbitone sodium. The

The study reported that the IC50 values for (DPPH) scavenging study reported that psychopharmacological parameters were activity, superoxide radical scavenging activity, hydroxyl significantly influenced by the both doses of methanolic ion (OH) radicals scavenging activity, and NO scavenging extract.[28]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S188 Pandey, et al.: A phytopharmacological review on Ludwigia octovalvis

ANTI-INFLAMMATORY ACTIVITY accessed on 2018 Feb 03]. 8. Levin RA, Wagner WL, Hoch PC, Nepokroeff M, Murugesan et al. reported that the methanolic extract of the Pires JC, Zimmer EA, et al. Family-level relationships whole part of J. suffruticosa showed dose-dependent anti- of Onagraceae based on chloroplast RBCL and NDHF inflammatory activity by carrageenin, serotonin-induced data. Am J Bot 2003;90:107-15. paw edema model, and cotton pouch granuloma model. 9. Barua IC. The genus Ludwigia (Onagraceae) in India. The study reported that the extract at a dose of 100, 200, Rheadea 2010;20:59-60. and 300 mg/kg body weight showed dose-dependent anti- 10. Perera PC, Nilanthi D. Review of major abundant weeds inflammatory activity in rats.[29] of cultivation in Sri Lanka. IJSRP 2015;5:2250-3153. 11. Lin WS, Wang JC, Wang PY, Chen JY, Chen LY, Lin CH, et al. The anti-aging effects of Ludwigia octovalvis ANTHELMINTIC ACTIVITY on drosophila melanogaster and SAMP8 mice. AGE 2014;36:689-703. Mythreyi et al. studied the methanolic extract of root of 12. Yakob HK, Uyub AM, Sulaiman SM. Immune- J. suffruticosa for anthelmintic activity against Pheretima stimulating properties of 80% methanolic extract of posthuma and Ascaris lumbricoides parasites. This study Ludwigia octovalvis against Shiga toxin-producing reported that the plant extract at a concentration of 1%, 2%, E. coli O157:H7 in Balb/c mice following experimental 3%, and 5% was evaluated against both worms and only infection. J Ethnopharmacol 2015;172:30-7. 13. Bhagyaleena P, Gopalon R. Aquatic medicinal plants 5% concentration of the extract was 100% effective against in ponds of Palakkad, Kerala. India J Pharm Biol Sci earthworm and 90% effective against flat worm.[30] 2012;2:29-35. 14. Murugesan T, Manikandan L, Suresh KB, Pal M, Saha BP. Evaluation of diuretic potential of Jussiaea suffruticosa, CONCLUSION extract in rats. Indian J Pharm Sci 2000;62:150-1. 15. Useful Tropical Plants Database; 2014. Available from: L. octovalvis is an important medicinal plant, having various http//www.tropical.theferns.info. [Last accesed on biological properties. Most of the information related to this 2018 Mar 04]. plant is documented. Isolation of new phytomolecules from 16. Kumar A, Kashyap P. Pharmacognostical and L. octovalvis and their efficacy in various diseases including phytochemical approach of Jussiaea suffruticosa Linn. mechanism of action to be evaluated for the effective use of IJPPR 2013;5:192-6. this herb. Further, lots of work to be explored about the plant 17. Mandal J, Rath J. Phytochemical and antioxidant for the benefit of human beings. activities of ethnomedicinal plants used by fisher folks of Chilika lagoon for Indigenous Phytotherapy. J Pharmacogn Phytochem 2015;3:55-65. REFERENCES 18. Yakob HK, Sulaiman SF, Uyub AM. Antioxidant and antibacterial activity of Ludwigia octovalvis on 1. Saxen M, Saxena J, Nema R, Singh D, Gupta A. Escherichia coli o157:h7 and some pathogenic bacteria. Phytochemistry of medicinal plants. J Pharmacogn World Appl Sci J 2012;16:22-9. Phytochem 2013;1:168-82. 19. Yan J, Yang XW. Studies on the chemical constituents 2. Jayapriya G, Gricilda SF. Phytochemical analysis and in herb of Ludwigia octovalvis. Zhongguo Zhong Yao antimicrobial efficacy of Rhinacanthus nasutus (l) Linn. ZaZhi 2005;30:1923-6. J Pharmacogn Phytochem 2015;3:83-6. 20. Chang CI, Kuo YH. Oleanane-type triterpenes from 3. Galor SW, Benzie FF. An Introduction to Its History, Ludwigia octovalvis. J Asian Nat Prod Res 2007;9:67-72. Usage, Regulation, Current Trends, and Research Needs. 21. Chang CI, Kuo CC, Chang JY, Kuo YH. Three new In: Herbal Medicine: Biomolecular and Clinical Aspects. oleanane-type triterpenes from Ludwigia octovalvis with 2nd ed. Taylor and Francis; 2011. cytotoxic activity against two human cancer cell lines. 4. Introduction and Importance of Medicinal Plants and J Nat Prod 2004;67:91-3. Herbs. Available from: http//www. nph.gov.in. [Last 22. Chen CP, Lin CC, Namba T. Screening of Taiwanese crude accessed on 2018 Mar 19]. drugs for antibacterial activity against Streptococcus 5. Yuan H, Ma Q, Ye L, Piao G. The traditional medicine mutans. J Ethnopharmacol 1989;27:285-95. and modern medicine from natural products. Molecules 23. Lin WS, Lo JH, Wang HW, Fan SZ, Wang PY. Ludwigia 2016;21: pii: E559 octovalvis extract improves glycemic control and 6. Wakdikar S. Global health care challenge: Indian memory performance in diabetic mice. J Ethnopharmacol experiences and new prescriptions. Electron J Biotechnol 2017;207:211-9. 2004;7:214-20. 24. Shyura LF, Tsunga JH, Chenb JH, Chiua CY, Lo CP. 7. The Integrated Taxonomic Information System on-line Antioxidant properties of extracts from medicinal plants Database. Available from: http://www.itis.gov. [Last popularly used in Taiwan. IJASE 2005;3:195-202.

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25. Yakob HK, Uyub AM, Sulaiman SM. Toxicological activity of Jussiaea suffruticosa extract in rats and mice. evaluation of 80% methanol extract of Ludwigia Pharm Pharmacol Commun 1999;5:663-5. octovalvis (Jacq.) P.H. Raven leaves (Onagraceae) in 29. Murugesan T, Pal M, Saha BP. Evaluation of anti- BALB/c mice. J Ethnopharmacol 2012;142:663-8. inflammatory potential of Jussiaea suffruticosa extract 26. Murugesan T, Rao B, Sinha S, Biswas S, Pal M, Saha BP. in albino rats. Des sources du savoir aux médicaments Anti-diabetic activity of Jussiaea suffruticosa extract in du future. Proceedings of the 4th European Congress on rat. Pharm Pharmacol Commun 2000;6:451-3. Ethnopharmacology; 2002; p. 395-8. 27. Murugesan T, Mandal SC, Bhakta T, Das J, Pal M, 30. Mythreyi R, Sasikala E, Murugan M, Geetha A. Saha BP. Evaluation of anti-pyretic potential of Anthelmintic activity of methanolic extract of roots of Jussiaea suffruticosa extract in rats. Phytomedicine Jussiaea suffruticosa. IJPRE 2017;4:1-2. 2000;7(3):231-4. 28. Murugesan T, Ghosh L, Das J, Pal M, Saha BP. CNS Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S190 Ayurvedic perspective on leucorrhea

Sucheta Mondal, Purnima Singh, Neha Shreya, Punam Kumara Department of Ayurveda Pharmacy, Rajiv Gandhi South Campus, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University

Abstract

Leucorrhea is a symptom not a disease, it appears at any stage of age. In Ayurveda, it is known as Shweta pradar. It is yellowish, whitish discharge occurring from vaginal route. These discharges possess offensive odor that causes itching, back pain, burning sensation, and weakness in whole body. The main causes of leucorrhea are hormonal imbalance, bacterial, fungal, yeast infection in vaginal region, eating spicy and fried food, unhygienic condition and suffering from diabetes, anemia, and hypothyroidism. In Ayurveda, it is caused by vitiation of kapha and vata kapha. It is described in

REVIEW ARTICLE REVIEW various ayurvedic texts such as Sharangdhar samhita, Charak samhita, Bhavaprakash, and Yogaratnakar. In Ayurveda, many ayurvedic formulations are available for the treatment of leucorrhea such as pradarari rasa, darvyadi kwatha, ashokarishta, and ashoka gritam. However, in western system of medicine, there is no permanent curing treatment.

Key words: Ayurvedic view, modern view, Shweta pradar

INTRODUCTION h. The chemical present in soap, detergent, and washing powder causes excessive discharge from vagina due to eucorrhea is whitish, yellowish, or alteration in pH level. greenish discharge occurring from the i. Use of birth control contraceptive pills, intrauterine vagina.[1] The vagina epithelium made device, poor immunity, and persons suffering from L diseases like hypothyroidism has greater risk of up stratified squamous epithelium and lamina propria. It is fibrovascular tube that connecting leucorrhea. the uterus.[1] The discharge originates from the 1. Infection: Caused by bacteria trichomonas vaginitis, vagina, ovaries, fallopian tube, and mostly from monilial vaginitis, bacterial vaginosis, and cervicitis. cervix.[2] These discharge having offensive Nature: (a) Cardy white in flakes, pruritic. (b) Gray-white, odor and creates problem such as itching non-pruritic, and fishy odor. (c) Frothy yellow discharge. vulva, back pain, weakness, tiredness, anxiety, 2. Atrophic: Caused by post-menopausal. tissue inflammation, and burning sensation.[3,4] Nature: (a) Not prominent discharge. (b) Irritation is Leucorrhea basically a symptom not a disease, prominent. this symptom may be appearing at any age.[5] 3. Foreign body: Caused by mechanical irritation and forgotten pessary, tampon. Nature: Often blood stained, purulent, copious, and THE MAIN CAUSE OF offensive odor. OCCURRING LEUCORRHEA The excessive secretion makes vulva moistness or staining brownish on drying, sometimes need to wear vulval pad. a. Hormonal imbalance, when estrogen level Sometimes, it becomes frustrating and makes women will be increased. uncomfortable, and they feel the urge to change their b. Fungal and yeast infection in vaginal undergarments in a day, excess perspiration occur and due region. to unpleasant odor, that creates embarrassing situation for c. Diabetes and anemia. women. Due to excessive discharge, excessive lubrication d. Eating spicy, fried food, and lots of the occurs which reduces the griping over penis that causes presence of carbohydrates. disappointing experience during sexual intercourse. There is e. Unhygienic condition that helps to grow bacteria within the vagina.[5] Address for correspondence: f. Leucorrhea occurs during pregnancy due to Sucheta Mondal, Rajiv Gandhi South Campus, Banaras increase in estrogen level.[6] Hindu University, Mirzapur, Uttar Pradesh, India. g. Moist and damp environment of vagina E-mail: [email protected] leads to growth of microorganisms.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S191 Mondal, et al.: Leucorrhea – Ayurvedic view the growth of microorganism due to moist environment and 3. Maintain of health and hygiene inflammation of vagina occurs due to excessive secretion.[5] 4. For pathological demonstration, common therapy is used in case of pelvic lesion Modern View on Leucorrhea 5. Estrogen level is balanced naturally 6. The discharge may be reduced by using such solution Leucorrhea can be defined as excessive whitish, yellowish which is pH balanced or greenish, sticky, viscous having offensive odor or odorless vaginal discharge occur from vagina, cervix, fallopian tube, and Antibiotics such as nystatin, natamycin, and povidone are ovaries and also due to physiological and pathological excess used for the treatment of leucorrhea. They act on bacteria and in female which may occur normally or due to infection. The kill them, thereby preventing leucorrhea. It has no significant women encounter normal fluid discharge which comprises all role in hormonal imbalance, neither have they imported worn out dead cells in the vaginal tract.[7] The chronic stage of the immune system. For the balancing of estrogen level, leucorrhea leads to pelvic inflammatory disease. i.e., hormonal balance Femiforte tablet is used.[13]

Types of Leucorrhea AYURVEDIC VIEW ON LEUCORRHEA 1. Physiological excess: a. During the time of pregnancy, vascularity increases Raktapradar, pradara, and asrgdara are the terms used for which leads to the increase in cervical gland bleeding from vagina but for white discharge word such secretion. as Shweta pradar or yonisrava has been used which is b. During menses, the level of estrogen increases which mentioned in various ayurvedic texts such as Sarangadhar cause increase in cervical gland secretary activity. samhita, Bhavaprakash, and Yogaratnakar. Vitiation of kapha c. Puberty - At the time of puberty, the level of leads to the development of symptom of all gynecological endogenous estrogen increases, thus causing disorder which is known as shweta pradara. In disease such excessive growth of endocervical epithelium leads to as atyananda, karnini, acarana, aticarana, slesmala, upapluta, congenital ectopy, thereby enhancing the secretion.[8] and prasramsini, specific clinic features are also described d. It is also observed in newborn female infants for 1 for each disease. Charak and Vagbhata have also prescribed or 2 month after birth due the exposure of estrogen symptomatic treatment for pandura asrgdara after describing [14] in womb. the treatment of all the gynecological disorder. Pandura e. Abundant secretions occur from Bartholin gland at asrgdara is described as shweta pradar and Indu as shukla [15] the time of sexual intercourse. (white) asrgdara by chakrapani. Explanation of Indu was f. It is caused due to natural defense mechanism of found to be doubtful since Asrgdara indicates discharge vagina to maintain pH balance in vagina. of blood which is red in color but cannot be white. For the treatment, the medicine prescribed is not specifically 2. Pathological excess: hemostatic but include kasaya rasa or astringent which have a. It can be defined as vaginal discharge due to infection capability of suppressing any discharge. It assumes that the or disease in female reproductive system.[9] word asrgdara also denotes the type of vaginal discharge, b. The vaginal infection may occur due to bacteria, along with bleeding from the vagina. Since shweta pradara virus, and fungi. is a symptom not a disease which was mentioned earlier, c. It may be caused due to infection vaginal mucosa by the etiopathogenesis of the main disease would also be Trichomonas vaginalis and Candida.[10] the etiopathogenesis of the symptoms which is described d. Hormonal imbalance and metabolically disorder previously. Aggregation of kapha occurs due to own vitiation may lead to its enhancement. factor or vitiation of rasa dhatu of reproductive system which is greatly influenced by excessive sexual intercourse, abortion or better living habit, or diet during menstruation.[16] SYMPTOMS Ayurvedic Treatment According to Classical Text It may include excessive vaginal discharge, itching in vaginal part, foul smell, irritability, digestive disturbance, black patch 1. The rice washing (tandulodaka) along with the kalka around eyes, anorexia,[11] polyuria, pain adhesiveness in of the khush grass drink for 3 consecutive days. 3 g of abdomen, pain during menstruation, constipation, body ache powder of the bhunimba along with 50 ml tandulodaka.[17] and thirst, fever, and vomiting.[12] 2. Bhasma of mercury or rasa sindura and decoction of the leave of vasaka plant.[18] Treatment: 3. Amla seed powder mixed with sugar candy powder and 1. Prevent the use of contraceptive for short time period then adds honey in it and take twice a day. 2. Surgical treatment such as electrocautery cryosurgery or 4. Make a churna of bark of Asoka and mix with equal trachelorrhaphy is used in case of cervical leucorrhea quantity of misri in it and then add 1-1 spoon in cow

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milk for 3 times in a day for few weeks.[19] activities such as excessive intercourse, abortion, unbalance 5. Take one glass of freshly extracted pomegranate juice diet, and improper timing during periods. Uncomfortability, one daily at least for 3 times in a day. uneasiness felt by women prove to a greater hindrance in the 6. Make a decoction of stem bark of vata and then mixed treatment. Various ayurvedic formulations are used for the with paste of lodhra (Symplocos racemosa).[20] treatment of leucorrhea such as kwatha, vati, varti, aveleha, 7. Take a fruit of Ficus racemosa and then make juice and asava, and arista. take with honey. After that, cooked rice, milk, and sugar are taken dietary supplement.[21] 8. Darvyadi kwath (Daru – haridra, Rasanjana, bark of CONCLUSION the adusa plant, mustaka, the pulp of bilva fructified, purified bhallataka, or red variety of sandalwood and Shweta pradar is whitish discharge occurring from the lotus.[22] vagina which does not possess burning sensation, pain, 9. Chandanadi churna (Red variety of sandal wood, and discomfort. It is caused due to various conditions such jatamansi, lodhra, usira, padma kesar, Nagapuspa, bark as hormonal imbalance, vaginitis, bacterial, fungal and of the bilva tree, bhadramustaka, raw sugar, natrabala yeast infection, and various gynecological disorders. Many patha, bark of kutaja plant, dried ginger, indrayava, formulations are available in Ayurveda such as Pradarari rasa, ativisha, dhataki flower, rasanjana, the pulp of stone of ashoka ghritam, Ashokarista for the treatment of leucorrhea mango fruit, the seed of jambu fruit, mocarasa, nilkamal, and results are good compared to western medicines. manjistha, root of plant samanga, lesser variety of cardamom, seed of pomegranate, honey, and rice washing.[23] REFERENCES 10. Pradarantaka rasa (purified mercury, purified sulfur vanga bhasma, rajat bhasma, kharpara bhasma, varatika 1. Available from: https://www.britannica.com/science/ [24] bhasma, lauha bhasma, and juice of ghrita kumara. leukorrhea encyclopedia britanica. [Last accessed on 11. Pradarari rasa (take one part of each of vanga bhasma, 2018, Feb 07]. lauha bhasma, purified ras sindur, root of the red lotus, 2. Jiménez-Castellanos MR, Zia H, Rhodes CT. [25] flower, and variety of sandalwood). Mucoadhesive drug delivery systems. Drug Dev Ind [26] [27] 12. Madhukadya avaleha, Sarvanga sundara ras, Pharm 1993;19:143-94. [26] [28] Patrangasava, Ashoka ghritam, and Ashokarista are 3. Duchěne D, Touchard F, Peppas NA. Pharmaceutical [29] important formulation use in leucorrhea. and medical aspects of bioadhesive systems for drug administration. Drug Dev Ind Pharm 1988;14:283-318. 4. Pepas NA, Buri PA, Surface interfacial and molecular DISCUSSION aspect of polymer bioadhesion on soft tissue. J Control Rel 1985;2:257-75. Women may suffer from gynecological disorder which 5. Bland PB, Rakoff A. The pharmacopeia and the physian may have vagina discharge due to vitiation of vata, pitta, leukoria clinical and leukoria clinical and therapeutic and kapha which may be caused due to involvement of diet aspect. JAMA 1940;115:1013. regime. The discharge may be profuse yellowish in color 6. Hameed HK. Hamdad Matab. New Delhi: Hamdard viscous, sometimes accompanied with offensive odor. It is Dawakhana; 1981. mentioned as gynecological disorder. Due to increased level 7. Dutta DC. Dc Dutta’s Textbook. Enlarged and of estrogen it leads to marked overgrowth of the endocervical Revised Reprint of Sixth edition. New Delhi, London, epithelium, may encroach onto the ectocervix which produces Philadelphia, Panama: Jaypee Brothers Medical congenital erosion and increased the secretion. Due to chronic Publichers (P) Ltd; 2013. p. 551. inflammation along with erosion, burning sensation, pain, and 8. Konar H. Dc Dutta’s Textbook of Gynecology 18. itching are also noticed. Itching may occur due to unhygienic Enlarged and Revised Reprint of Sixth edition. condition leading to the growth of microorganism. Increase New Delhi, London, Philadelphia, Panama: Jaypee in cervical gland secretion at the time of pregnancy may lead Brothers Medical Publichers (P) Ltd; 2013. p. 551. to vaginal discharge. At the time of puberty and menses, 9. Konar H. Dc Dutta’s Textbook of Gynecology 18. the level of estrogen increases in the body. Sometimes, Enlarged and Revised Reprint of Sixth edition. infection due to microorganism or disease in female New Delhi, London, Philadelphia, Panama: Jaypee reproductive system or hormonal imbalance may also lead Brothers Medical Publichers (P) Ltd; 2013. p. 552. to vaginal leucorrhea. According to Ayurveda development 10. Elkabbakh GT, Elkabbakh GD, Broekhuizen F, of symptom, gynecological disorder occurs due to vitiation Griner BT. Value of wet mount and cervical cultures at of vata kapha and kapha. Charak and Vagbhata determining the time of cervical cytology in asymptomatic women. leucorrhea as pandura asrgdara and they also describe some Obstet Gynecol 1995;85:449-503. sympyomatic treatment on leucorrhea. It may occur due to 11. Hameed HK. Hamdad Matab. New Delhi: Hamdard vitiation of kapha as mentioned earlier which is influence by Dawakhana; 1981. p. 95-6.

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12. Jackobsin L, Westrom L. Objectivised diagnosis of acute Varanasi: Chaukhambha Bharti Academy; 2006. pelvic inflammatory disease, Diagnostic and prognostic p. 770-772. value of routine Laparoscopy. Am J Obstet Gynecol 22. Shastri KN, Pandey GS, editors. Charak Samhita 1969;105:1088-98. Vidyotini. 1st ed. Chikitsa sthana 30/116. Varanasi: 13. Konar H. Dc Dutta’s Textbook of Gynecology 18. Chaukhambha Bharti Academy; 2006. p. 770-772. Enlarged and Revised Reprint of Sixth edition. 23. Chaukhambha Sanskrit Bhawan. Bhaisajya ratnavali New Delhi, London, Philadelphia, Panama: Jaypee of Shri Govinda Dasji. Vol. 3. Ch. 66/24. Varanasi: Brothers Medical Publichers (P) Ltd; 2013. p. 553 Chaukhambha Sanskrit Bhawan; 2006. p. 342. 14. Tiwari P. Ayurvedic Prasuti Tantra Evam Stei rog. Vol. 2. 24. Chaukhambha Sanskrit Bhawan. Bhaisajya ratnavali New Delhi, India: Chaukhamba Publication; 2009. of Shri Govinda Dasji. Vol. 3. Ch. 66/51. Varanasi: p. 268. Chaukhambha Sanskrit Bhawan; 2006. p. 347. 15. Shastri KN, panday GS, editiors. Charak Samhita. Vidyotini 25. Chaukhambha Sanskrit Bhawan. Bhaisajya ratnavali Hindi Commentary. Chikitsa Sthana 30/116. 1st ed., Vol. 2. of Shri Govinda Dasji. Vol. 3. Ch. 66/57-61. Varanasi: Varanasi: Chaukhamba Bharati Academy; 2006. Chaukhambha Sanskrit Bhawan; 2006. p. 348. 16. Tiwari P. Ayurvedic Prasuti Tantra Evam Stei rog. Vol. 2. 26. Chaukhambha Sanskrit Bhawan. Bhaisajya ratnavali New Delhi, India: Chaukhamba Publication; 2009. of Shri Govinda Dasji. Vol. 3. Ch. 66/56. Varanasi: p. 267. Chaukhambha Sanskrit Bhawan; 2006. p. 348. 17. Chaukhambha Sanskrit Bhawan. Bhaisajya ratnavali 27. Chaukhambha Sanskrit Bhawan. Bhaisajya ratnavali of of Shri Govinda Dasji. Vol. 3. Ch. 66/3. Varanasi: Shri Govinda Dasji. Vol. 3. Ch. 66/122-126. Varanasi: Chaukhambha Sanskrit Bhawan; 2006. p. 339. Chaukhambha Sanskrit Bhawan; 2006. p. 357. 18. Chaukhambha Sanskrit Bhawan. Bhaisajya ratnavali 28. Chaukhambha Sanskrit Bhawan. Bhaisajya ratnavali of of Shri Govinda Dasji. Vol. 3. Ch. 66/18. Varanasi: Shri Govinda Dasji. Vol. 3. Ch. 66/103-109. Varanasi: Chaukhambha Sanskrit Bhawan; 2006. p. 341. Chaukhambha Sanskrit Bhawan; 2006. p. 356. 19. Charak Samhita, Chikitsha Sthana. Vol. 2. Varanasi: 29. Chaukhambha Sanskrit Bhawan. Bhaisajya ratnavali of Chaukhambha Sanskrit Bhawan. p. 858. Shri Govinda Dasji. Vol. 3. Ch. 66/144-118. Varanasi: 20. Chaukhambha Sanskrit Bhawan. Bhaisajya ratnavali Chaukhambha Sanskrit Bhawan; 2006. p. 357. of Shri Govinda Dasji. Vol. 3. Ch. 66/4. Varanasi: Chaukhambha Sanskrit Bhawan; 2006. p.388. 21. Shastri KN, Pandey GS, editors. Charak Samhita Vidyotini. 1st ed., Vol. 2. Chikitsa sthana 30/116. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S194 Diabetic retinopathy - A vision - threatening complication of diabetes mellitus and its management by Triphala - An evidence-based review

Sudheer Kumar Kushwaha1, B. Mukhopadhyay1, Roli Sarjuprasad Mishra2 1Department of Shalakya Tantra, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India, 2Department of Dravyaguna, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

REVIEW ARTICLE REVIEW Abstract

As we are living in 2018, a huge population of the world is fighting with a serious metabolic disorder - diabetes. As per the WHO survey, 415 million people of the world were diabetic in 2015. The rate of progression of diabetes is continuously rising. Diabetes mellitus is a metabolic syndrome characterized by chronic hyperglycemia along with disturbance of carbohydrate, protein, and fat metabolism. Diabetes mellitus can give birth to some serious complications such as diabetic ketoacidosis, stroke, cardiovascular diseases, chronic kidney disease, diabetic foot, diabetic nephropathy, diabetic neuropathy, and diabetic retinopathy (DR). DR is a microangiopathy, in which the integrity of the retinal precapillaries, arterioles, and venules becomes disturbed and either due to hemorrhage or occlusion the clinical presentation of DR appears. Triphala is a famous drug of Ayurveda, which is described in Brihattrayi, Laghuttrayi, Nighantus, and many other literatures of Ayurveda. In many places, it is used for Prameha. Triphala and its ingredients are quoted as Chakshushya in many places. Many studies have been done on Triphala in different parts of our country as well as outside the country which shows the hypoglycemic, anti-inflammatory, antioxidant, free radical scavenging, and anti-vascular endothelial growth factor activity of Triphala and favors the fact that Triphala has very significant role in the management of diabetes as well as DR.

Key words: Chakshushya, diabetes, diabetic retinopathy, hyperglycemia, microangiopathy, Prameha, Triphala

INTRODUCTION an estimated 31,705,000 diabetics in the millennium year which is estimated to grow by over 100% to 79,441,000 by n the 21st century, our world is fighting 2030. According to the International Diabetes Federation with some specific type of health issues Atlas 2015, an estimated 69.2 million Indians are diabetic, which are grouped in lifestyle disorders which as per the WHO assessment stood at 63 million in the I year 2013. The estimates depict that diabetes prevalence has such as diabetes mellitus and hypertension. Developed countries as well as developing alarmingly doubled and so far has grown by over 100% in countries are suffering from these serious the past 15 years. problems. According to the WHO, “diabetes” or “diabetes mellitus” Data say that approximately 415 million is a group of metabolic disorders which depend on multiple people in the world had diabetes in 2015,[1] factors and characterized by chronic hyperglycemia Type 2 diabetic patient having 90% share of along with disturbance of carbohydrate, protein, and fat it.[2,3] This represents about 8.3% of the adult metabolism.[9] These abnormalities occur due to defects in population,[3] with an equal percentage of both insulin secretion, insulin action, or both. Symptoms of high male and female.[4] The rate of progression is continuously rising.[5] Due to diabetes, a Address for correspondence: person’s risk of early death doubles.[6] From Dr. Sudheer Kumar Kushwaha, Room No. 292, Sushrut 2012 to 2015, approximately 1.5–5.0 million Hostel, Trauma Centre, Institute of Medical Sciences, people died due to diabetes per year.[1,7] In Banaras Hindu University, Varanasi - 221 005, 2014, global economic cost of diabetes was Uttar Pradesh, India. E-mail: [email protected] estimated to be US$612 billion.[8] India had

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S195 Kushwaha, et al.: Diabetic retinopathy and its management by an indigenous drug- Triphala blood glucose include polydipsia, polyphagia, and polyurea. of DR in a scientific manner with the help of Ayurvedic If diabetes mellitus is left untreated for pronged time, it literature and research works which are published in different becomes the root cause of several other serious conditions standard journals. such as diabetic ketoacidosis, hyperosmolar hyperglycemic state, cardiovascular disease, stroke, chronic kidney disease, diabetic foot, diabetic nephropathy, diabetic neuropathy, and WHAT IS DR? diabetic retinopathy (DR).[6] DR is a microangiopathy affecting the retinal precapillaries, DR is a microangiopathy which occurs due to arterioles, and venules.[10-12] It is the complication of hyperglycemia (micro = small, angio = vessels, and diabetes mellitus. In diabetes mellitus, if the blood glucose pathy = abnormality). It involves damage to the retinal level is increased for a prolonged time, microvascular and capillaries. It is a progressive disease. Early disease may macrovascular changes occur in whole body. These changes not cause symptoms, but in advance stage, patient may loss also occur in eyes. The retina which is the innermost his vision completely.[10-12] DR is a leading cause of legal tunic of the eyeball has 10 layers. The outer four layers blindness and visual disability in the working age group in are supplied by choriocapillaris and inner six layers are industrialized country.[13] supplied by branches of central retinal artery. The retina has two distinct structures - one is optic disc and another is Retina is the innermost tunic of the eyeball which is very thin Macula lutea. Optic disc is pale-pink, well-defined circular delicate and transparent membrane. It is the most developed area of approximately 1.5 mm diameter. At the optic disc, and sensitive part of the eye.[14] We can see objects clearly with all the retinal layers terminate except the nerve fibers, accurate shape, size, and color due to the great anatomical which pass through the lamina cribrosa (sieve-like sclera) structure of the retina. When structure of retina becomes to run into the optic nerve. Optic nerve transmits the visual abnormal with or without visual disturbance, condition is sensation to the visual cortex of the brain. Macula lutea is referred as DR. situated in the posterior pole of the eyeball, temporal to the optic disc, and having a diameter of 5.5 mm. The central Triphala is an Ayurvedic drug which have three components - depressed part of the macula is known as fovea centralis and Amalaki (Emblica officinalis Gaertn.), Haritaki (Terminalia having 1.5 mm diameter. It is the most sensitive part of the chebula Retz.), and Bibhitaki (Terminalia bellerica Roxb.). retina. In its center, a central shining pit foveola is present Triphala has great clinical significance. It is given by an (diameter - 0.35 mm). An area of about 0.8 mm is known as Ayurvedic practitioner for many diseases or many purposes. foveal avascular zone because it does not have any retinal As per our Ayurvedic classics, Triphala can be categorized capillaries.[14] under Tridoshaghna Rasayana as it provides energy to the body and pacifies all three Sharir doshas (vata, pitta and kapha).[15] Acharya Charaka said that Rasayanas have BASIC PATHOPHYSIOLOGY OF DR the qualities of supporting strength and immunity. Hence, [FIGURES 1-3][20] due to these properties, Triphala can be given to very young, the infirmed, and to the old one. Triphala has also When hyperglycemia persists for long time, vascular and digestive, Shukral, mild laxative at normal dose, bowel hematological changes occur. They are responsible for tonic at low dose, purgative at high dose, antispasmodic, microvascular leakage and microvascular occlusion. expectorant, and bronchodilator properties.[16] Triphala has also antidiabetic property, which has been proven by many DR is also caused by polyol pathway-mediated oxidative studies. It has also a role in the improvement of impaired damage. Aldose reductase is found in high concentration in vision. pericytes. It converts glucose to sorbitol. Sorbitol has very low tendency of diffusion. Hence, it accumulates within the cell and Properties of Triphala and its uses have mentioned in causes electrolyte imbalance and microvascular abnormalities.[20] Brihattrayi, Laghuttrayi, different Nighantus, and many other literature of Ayurveda. Acharya Charaka has described Oxidative stress - It occurs due to an imbalance between oxygen Phalatrikadi Kwatha for the treatment of Prameha free radicals and antioxidant defenses in biological system. Due (diabetes). Triphala is also the constituent of the Phalatrikadi to this development of DR and progression, both occur.[20] Kwatha.[17] Acharya Sushruta has described Amalki and Haritaki as Chakshushya drugs.[18] Acharya Vagbhatta also Vascular endothelial growth factors (VEGFs) are the major said that Triphala strengthens eyes and improves vision. factor for producing DR. VEGFs are responsible for both These are just examples.[19] Many literary works have been vasculogenesis and angiogenesis. Insulin such as growth done previously on Triphala. Many studies have done to factors and angiopoietin 1 and 2 are also cause by DR.[20] prove the effect of Triphala in diabetes and diabetes-related ocular complication - DR. In this paper, we are trying to DR is of four types - non-proliferative DR (PDR), PDR, establish the fact that Triphala is beneficial for the treatment diabetic macular edema, and advanced diabetic eye disease.

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(a)Capillary basement membrane thickening, (b) capillary endothelial cell damage, (c) RBCs deformation with rouleaux formation, (d) platelet stickiness increased

Microvascular occlusion a b c Retinal Ischimia Figure 3: (a) Normal fundus, (b) non-proliferative diabetic Retinal Hypoxiainfarction retinopathy, (c) proliferative diabetic retinopathy

Arteriovenous shunt (IRMA) Increased VEGFcotton wool spot balance all doshas by its trophism. Amalaki is guru and

Neovascularization ruksh in property while both Haritaki and Bibhitaki are laghu and ruksha.[21] Vitreous haemorrhage fibrovascular bands neovascular glaucoma

Tractional retinal detachment THERAPEUTIC EFFECTS OF TRIPHALA Diminution of vision, distortion in shape of objects, loss of vision WITH THEIR ACTIVE INGREDIENTS Loss of pericytes Studies have validated a number of potential uses of Triphala, which include free radical scavenging, antioxidant, Microvascular leakage anti-inflammatory, wound healing, hypoglycemic, and radioprotective effects.[22] Many other qualities are also found in Triphala, but we quoted here only those which are Haemorrhage oedema beneficial for DR. Triphala may also maintain homeostasis of the endocrine system which very much concerned with [22] Diffused focal mixed diabetes.

Diminution of vision, distortion in shape of objects, loss of vision The major constituents of this herbal formula are the chebulinic acid, gallic acid, ellagic acid, and tannins which Figure 1:Two pathways for occurrence of Diabetic retinopathy- are potent antioxidants that may account, at least in part, for (i) microvascular occlusion and (ii) microvascular leakage the observed anti-VEGF and immunomodulatory activity of the formula.[23,24] Triphala also contains some other bioactive Hyperglycaemia compounds such as saponins, anthraquinones, flavonoids Oxidative stress Inflammation PKC activation AGEs Polyol pathway (e.g., quercetin and luteolin), various carbohydrates, amino acids, and fatty acids.[25] In addition, an alcoholic extract of Activation of cytokines and growth factorsDysfunction of vascular and neuronal cells Triphala such as chebulinic acid is also transformed by the microbes of human gut into bioactive metabolites, which have Neural dysfunctionVascular permeabilityDiabetic Retinopathy demonstrated the potential effect in vitro to prevent oxidative damage and may give beneficial results in DR cases.[26] Retinal hypoxia

Neovascularisation WHAT DOES TRIPHALA IN DR Vision loss

Figure 2: Diagrammatic representation of different pathways VEGFs are one of the important causes of DR. Triphala contains responsible for Diabetic retinopathy. chebulinic acid as one of the active constituents. A study has done by some scientist to find the effect of chebulinic In DR, vision loss is mainly due to macular edema. Macula acid on VEGF which shows a great result. They said after is responsible for central vision as well as accurate vision. If the experiment that Triphala and chebulinic acid are natural [23] macula gets swelled, visual disturbance occurs.[10-12] inhibitors of VEGFs. They extracted chebulinic acid from Triphala Churna. Some scientists used aqueous and alcoholic extracts of Triphala and their active compounds chebulagic acid and chebulinic acid to prevent the retinal pigment PHARMACOLOGY OF TRIPHALA epithelial cells by inhibiting SMAD-3 phosphorylation.[27]

Triphala is Pancharasatmaka Aushadh Dravya that means, Triphala has anti-inflammatory property. Anti-inflammatory except salt, rest five types of rasa are present, i.e., sweet, effect of Triphala was studied by a group of some Thai sour, pungent, bitter, and astringent. The vipaka or post- doctors and proved by them.[28] It reduced both acute and digestive effect of the Triphala is sweet. Triphala can chronic inflammation.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S197 Kushwaha, et al.: Diabetic retinopathy and its management by an indigenous drug- Triphala

Many studies have done to show hypoglycemic property Available from: http://www.diabetesatlas.org/. [Last of Triphala. In one study, 30 diabetic patients were treated retrieved on 2016 Mar 21]. with Triphala (the three myrobalans). Triphala has given as 2. Melmed S, Polonsky KS, Larsen PR, Kronenberg HM. a supplement for 45 days with buttermilk after 2 h of dinner. Williams Textbook of Endocrinology. 12th ed. After this therapy, the result shows significant lowering in the Philadelphia: Elsevier/Saunders; 2011. p. 1371-435. blood glucose levels at 5 g level quantity (both fasting and 3. Yuankai S, Frank BH. The global implications of postprandial). Triphala has menthol and sorbitol as active diabetes and cancer. Lancet 2014;383:1947-8. ingredient which is believed to have hypoglycemic effect.[29] 4. Vos T, Flaxman AD, Naghavi M, Lozano R, Michaud C, Ezzati M, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: ANTIOXIDANT ACTIVITY OF TRIPHALA IN A systematic analysis for the Global Burden of Disease ANOTHER OCULAR DISORDER Study 2010. Lancet 2012;380:2163-96. 5. International Diabetes Federation. Annual Report Triphala has the potential to maintain the eye health due to 2014 (PDF). IDF. International Diabetes Federation; its antioxidant property. Vitamin C and flavonoids are found Available from: http://www.idf.org/sites/default/files/ in Triphala in very rich amount. Triphala has also a role IDF-2014-Annual-Report-final.pdf. [Last retrieved on in cataracts. In a study when Triphala is used in selenite- 2016 Jul 13]. induced cataracts in mice as a pretreatment, it shows very 6. WHO. “Diabetes Fact sheet N 312”. Geneva: WHO; good results. Glutathione levels in eye lenses become 2013. Available from: http://www.who.int/mediacentre/ normal by the use of Triphala. Activities of some antioxidant factsheets/fs312/en/. [Last retrieved on 2014 Mar 25]. enzymes are also enhanced by Triphala, such as catalase, 7. WHO. The Top 10 Causes of Death Fact sheet N 310. glutathione peroxidase, glutathione-S-transferase, and Geneva: World Health Organization; 2013. superoxide dismutase. In this study, 100% mice of the control 8. International Diabetes Federation. IDF Diabetes Atlas group developed cataracts, but only 20% of the mice which (PDF). 6th ed. International Diabetes Federation; 2013. were pretreated with Triphala developed cataracts. This p. 7. preventive effect was may be due to the antioxidant activity 9. WHO. “About diabetes”. Geneva: World Health of the Triphala.[30] Organization; 2014. Available from: http://www.who. int/diabetes/action_online/basics/en/. [Last retrieved on Triphala can be used as many doses form such as Churna, 2014 Apr 04]. guggulu, ghrita, and aasav. Triphala has also Meda Shamak 10. Bawling B. Kanski’s Clinical Ophthalmology. China: property. Meda is also related to Prameha and Pramehajanya Elsevier; 2016. p. 520-37. Updrava diabetic retinopathy, so it is beneficial for DR. 11. Sihota R, Tandon R. Parsons’ Disease of the Eye. Haryana: Elsevier; 2016. p. 312-7. Acharya Charaka has given the Prameha a special position 12. Khurana AK, Khurana B. Comprehensive among diseases as he described it under eight major diseases. Ophthalmology. New Delhi: New Age International Prameha is a group of 20 diseases; diabetes is also a group of Publishers; 2014. p. 274-9. many metabolic disorders. DR is a severe vision-threatening 13. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the complication of diabetes or Prameha. In initial stage of DR, prevalence of diabetes for 2010 and 2030. Diabetes Res patient may complain for mild diminution of vision, but with Clin Pract 2010;87:4-14. the progression of disease, worsening of visual problems also 14. Khurana AK, Khurana I. Anatomy and Physiology of occur, and in extreme stage, patient becomes blind. Triphala Eye. New Delhi: CBS Publishers and Distributors; 2015. has great potency to treat diabetes as well as DR. Triphala has p. 166-95. hypoglycemic, anti-inflammatory, free radical scavenging, 15. Agnivesha, Chakrapanidatta, Sarma RM, Dash B. antioxidant, wound healing, and radioprotective properties. Charaka Samhita: Text with English Translation It also contains some specific constituents which have anti- and Critical Exposition Based on Chakrapanidatta’s VEGF activity. All these effects have proven by several Ayurveda Dipika. 1st ed. Varanasi, India: Chowkhamba studies. Some of them are mentioned in our study. Hence, we Sanskrit Series Office; 1976. can conclude now that Triphala has very significant role in 16. Peterson CT, Denniston K, Chopra D. Therapeutic uses the management of DR and we should prescribe the different of Triphala in ayurvedic medicine. J Altern Complement doses forms for the treatment of DR. But still, there is a need Med 2017;23:607-14. of some additional research work. 17. Dridhabala AC. In: Pandey K, Chaturvedi GN, editor. Charak Samhita, Chikitsa Sthsna, Prameha Chikitsa Adhyaya. Reprint ed. Varanasi: Chaukhambha Bharati REFERENCES Acdamy; 2012. p. 227-47. 18. Chandrata S. In: Shashtri KA, editor. Sushrut Samhita, 1. IDF. International Diabetes Federation. “Update 2015”. Sutra Sthana, Annapanavidhi Adhyaya. Reprint ed. IDF. International Diabetes Federation; 2016. p. 13. Varanasi: Chaukhambha Sanskrit Sansthana; 2016.

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p. 241-92. 2014;76:467-75. 19. Vagbhatta L, Hridaya A. In: Srikantha Murthy KR, editor. 26. Olennikov DN, Kashchenko NI, Chirikova NK. In vitro Sutra Sthana, Matrashitiya Adhyaya 8/44. Varanasi: bioaccessibility, human gut microbiota metabolites and Chaukhambha Krishnadas Acadamy; 2014. p. 132. hepatoprotective potential of chebulic ellagitannins: 20. Tarr JM, Kaul K, Chopra M, Kohner EM, Chibber R. A case of Padma hepaten formulation. Nutrients Pathophysiology of diabetic retinopathy. ISRN 2015;7:8456-77. Ophthalmol 2013;2013: Article ID 343560, 13. 27. Sivasankar S, Lavanya R, Brindha P, Angayarkanni N. 21. Baliga MS, Meera S, Mathai B, Rai MP, Pawar V, Aqueous and alcoholic extracts of Triphala and their Palatty PL. Scientific validation of the ethnomedicinal active compounds chebulagic acid and chebulinic properties of the Ayurvedic drug Triphala: A review. acid prevented epithelial to mesenchymal transition in Chin J Integr Med 2012;18:946-54. retinal pigment epithelial cells, by inhibiting SMAD-3 22. Pandey K, Chaturvedi GN, editor. Agnivesha, Charaka, Phosphorylation. PLoS One 2015;10:e0120512. Dridhbala. Charak Samhita, Chikitsa Sthana, Rasayana 28. Sireeratawong S, Jaijoy K, Soonthornchareonnon N. Adhyaya. Reprint ed. Varanasi: Chaukhambha Bharati Evaluation of anti-inflammatory and antinociceptive Acdamy; 2012. p. 1-21 activity of Triphala recipe. Afr J Tradit Complement 23. Lu K, Chakroborty D, Sarkar C, Lu T, Xie Z, Liu Z, et al. Altern Med 2013;10:246-50. Triphala and its active constituent chebulinic acid are 29. Rajan SS, Antony S. Hypoglycemic effect of Triphala natural inhibitors of vascular endothelial growth factor-a on selected non-insulin dependent Diabetes mellitus mediated angiogenesis. PLoS One 2012;7:e43934. subjects. Anc Sci Life 2008;27:45-9. 24. Lee HS, Won NH, Kim KH, Lee H, Jun W, Lee KW. 30. Gupta SK, Kalaiselvan V, Srivastava S, Agrawal SS, Antioxidant effects of aqueous extract of Terminalia Saxena R. Evaluation of anticataract potential of chebula in vivo and in vitro. Biol Pharm Bull Triphala in selenite-induced cataract: In vitro and in vivo 2005;28:1639-44. studies. J Ayurveda Integr Med 2010;1:280-6. 25. Belapurkar P, Goyal P, Tiwari-Barua P. Immunomodulatory effects of Triphala and its individual constituents: A review. Indian J Pharm Sci Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S199 Ayurvedic review on some medicinal plants, metals, and minerals having anticancer property

Sukanya Yadav Department of Pharmacy Ayurveda, Rajiv Gandhi South Campus, Banaras Hindu University, Mirzapur, Uttar Pradesh, India

Abstract

Cancer is a major health problem in both developed and developing countries. After cardiovascular disease cancer

REVIEW ARTICLE REVIEW is the second most common cause of death. In cancer abnormal growths of cells in our bodies occur. Cancer is a complex group of diseases in which involve cell transformation proliferation, invasion, metastasis, and angiogenesis. There is various plant product used in the treatment of cancer. The major problem of chemotherapy is toxicity of the drug. In human being, it is caused by exposure of toxic materials, some genetic factors, and viral infections. The purpose of this review is to explore the medicinal plants, metals, and minerals for treatment of cancer.

Key words: Cancer, medicinal plants, metals, minerals, models for anticancer property

INTRODUCTION Over the past decade, herbal medicine has become a topic of global importance, making an impact on both international atural products have been used in trade and world health.[5] The major cause of cancer is various diseases for several of years.[1] smoking, hormones, and chronic infections lead chronic NCancer is abnormal growth of cells and inflammation.[6] Cancer can affect any part of the body, and it these cells usually invade and destroy normal is termed as malignant tumors and neoplasm. cells. These cells are generated due to an imbalance in the body and treated by correcting There are six characteristics of malignancy: the imbalance. Breast cancer is developed one • Insensitivity of antigrowth signals out of 30 women in the country. Colon cancer • Enabling of limitless replicative potential is second most cause of death in US1.[2] Prostate • Self-sufficiency iν growth signalling cancer is frequently diagnosed cancer among • Activation of metastasis and invasioν of tissue the men in US, second is skin cancer with • Evasion of apoptosis an estimated 180,000 new cases and 37,000 • Sustainment and induction of angiogenesis.[7] deaths expected by American cancer society 6 each year. About 42% male and 18% female Every year millions of new cancer cases are found. After cancer deaths caused using of tobacco-related several years diagnosis it was found that cancer cells [3] products. Terrestrial plants have been used as invade and destroyed normal cells.[1] Chemotherapy is medicines in India, Egypt, China, and Greece a major treatment for the control of advanced stages of from ancient time based on ACS report 2014, malignancy.[8] Several herbal plants they maintain vitality nearly 1 in every 4 deaths can be caused by and health of individual and also cure the diseases including cancer with a possibility of 585,720 deaths due cancer.[9] According to the WHO, several people of developing to cancer this year in USA.Now a days herbal countries used traditional medicines for their primary health medicine are said to be potential source of need. According to a recent survey, 60% cancer patient used anticancer agents and widely used across the herbs and vitamins as a therapy.[10] Because of high death rate globe due to their therapeutic efficacy and wide applicability with least side effects. Medicinal Address for correspondence: plants play a role in the health-care system of Sukanya Yadav, Department of Pharmacy Ayurveda, large proportion of world populations.[4] The Rajiv Gandhi South Campus, Banaras Hindu University, anticancer of activity of plants is due to the Mirzapur, Uttar Pradesh, India. Phone: 8840680301. presence on antioxidant property in them, and E-mail: [email protected] they are natural source of anticancer agents.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S200 Yadav: Anticancer property having plants, metals and minerals associated with cancer and because of serious side effects of the major body system loses mutual coordination and cause chemotherapy and radiation therapy, several cancer patients morbid conditions.[1] Classical Indian Ayurvedic drugs such as seek complementary method of treatment.[11] Amritaprasham, Ashwagandha Rasayana, Brahma Rasayana, Chyavanprasha, Narasimha Rasayana, and Triphala Churna were found to be radioprotective in cancer treatment.[13] In WHAT CAUSES CANCER Ayurveda neoplasm can be classified on the basis of clinical symptoms related to tridoshas.[1] Cancer can be caused by a number of genetic alternation. Mutation in tumor suppressor gene and oncogenes represent Group 1: Diseases they are not cancer but considered as the primary genetic lesions - their activation and inactivation, a malignancy such as growth and ulcer Examples: respectively, trigger carcinogenesis. Cancer can be occurring Tridosaja gulma, ashadya galganda (thyroid tumor), by a mutation in DNA, which instructs the cells how to grow ashadya udara rog, and abdominal tumor like carcinomas and divide. Normal cells have the ability to repair mutations of the liver and stomach.[1] in DNA. However, mutations cannot be repaired and cause to Group 2: Diseases are having possibility of malignancy such grow the cells to become cancerous.[1] as ashadya pradar, ashadya kamla, and visarpa.[1] Group 3: Diseases are having clear malignancy including granthi and arbhuda such as raktaarbhuda (leukemia), ENVIROMENTAL FACTORS ashadya vrana (malignant ulcer), mukharbuda (oral cancer), and mamsarbuda (sarcoma).[1] Environmental factors including diet, smoking, radiations in our homes, infectious diseases as well as chemicals and There are many types of cancer treatment such as surgery with workplace along with trace level of pollutants in drinking chemotherapy and/or radiation therapy. You may also have [14] water, food, and in air.[1] The cancer risk becomes highly immunotherapy, targeted therapy, or hormone therapy. increase where workers are exposed to ionizing radiations, certain metals, carcinomas chemicals, and other specific Plants having Anticancer Activity substance exposed at low levels.[1] 1. Brahma Manduki (Centella asiatica): Apocynaceae Other factors, which are affect like tobacco use, not enough family. It is suppressed mouse lung fibroblast cell physical activity, unhealthy diet; however, the degree of risk proliferation, and oral administration slowed the ascites from pollutants depends on the intensity, concentration, and tumors.[15] it has several compounds such as vallerine, exposure of radiations.[1] ascorbic acid, flavonoids, and sterol.[16] If pretreatment of these plant occurs, then it increases survival time of animals and protects the damage liver from radiation.[22] AYURVEDIC CONCEPT 2. Pomegranate (Punica granatum): Lythraceae family. Pomegranate has phenolic compounds, ellagic acid, Charaka and Sushruta are two well-known ayurvedic text and ellagitannins that convert urothilins metabolicly by describe cancer as a arbuda (major neoplasm) and granthi the gut of microbiota. It interferes with cell cycle and (minor neoplasm), and it is inflammatory or non-inflammatory inhibit proliferate of cancer cell and induce apoptosis. swelling.[12] Aspects of the practice of Ayurveda - Charaka Urothilins found in colorectal (CRC) patients in high Samhita (1100 plants), Sushruta Samhita (1270 plants), and concentration.[16] Astanga Hridaya (1150 plants).[13] Ayurveda is known as 3. Talispatra (Taxus baccata): Taxaceae family. Taxol as Astanga Ayurveda, which means that which is made up of a natural cytotoxic compound has been extracted and 8 parts.[13] The 8 major divisions of Ayurveda are as follow used in the treatment of cancer. In which cytotoxic effect as: (a) Kayachikitsa (Internal Medicine), (b) Kaumar Bhritya of natural resources, branchlets, bark, and fruits of two (Pediatrics), (c) Bhootavidya (Psychiatry), (d) Shalakya different species of conifers was identified and collected. (Otorhinolaryngology and Ophthalmology), (e) Shaly The cytotoxic effect of their hydroalcoholic extract was (Surgery), (f) Agada Tantra (toxicology), (g) Rasayana determined on three human tumor cells. T. baccata (Geriatrics), and (h) Vajikarana (Aphrodisiacs and Eugenics).[16] and its anticancer activity against breast cancer cell In the ayurvedic text, three doshas are described vata, pitta, lines (MDA-MB 231 and MCF-7) and normal human and kapha, i.e., nervous system (vata or air), venous system epithelial cell line (HEK-293) have been studied. (pitta or fire), and arterial system (kapha or water); they are Few novel taxoids such as etoposide, elliptinium, mutually coordinate and responsible for the normal functions homoharringtonine, roscovitine, and flavopiridol derived of the body.[13] In neoplasm (vataja, pittaja, and kaphaja) one from naturally occurring 2-DAT-J and screening for their or two of three body system are out of control, and it is not too anticancer activity.[17] harmful because the body still trying to coordinate with these 4. Yashtimadhu (Glycyrrhiza glabra). Fabaceae family. system.[12] Tridoshic arbhuda is usually malignant because In vitro cytotoxic screening of standard glycyrrhetic

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acid was carried using three different extracts (methanol, [25] There are several explanations for the mechanism chloroform, and water) of drug through MTT method. of action of arsenic trioxide. It induces p53 dependent The percentage viability of two different cell lines was G1 and G2/M cell cycle arrest through an activation 78.78% for MCF-7 cancerous cell line and 45.71% for of caspase.[26] Arsenic trioxide also induces apoptosis Vero normal line.[17] Cell viability of glycyrrhetic acid and cell cycle arrest.[27] The anti-carcinogenic effect in three different extracts was determined by two-fold of arsenic trioxide may be related to the induction of try pan-blue method using two different cell lines Vero apoptosis.[28] Several cell lines are sensitive to arsenic normal cell and MCF7 cancerous cell. trioxide: Esophageal carcinoma cell, renal cell carcinoma 5. Haldi (Curcuma longa): Zingiberaceae family. It is used cell, and small cell lung cancer (Natural cytotoxic cells in ovarian cancer, gastrointestinal cancer, breast cancer, (Nc cells) Hydrocortisone (Hc cells)).[29] Arsenic trioxide lung cancer, melanoma, lymphoma, leukemia, and has been also shown to be active against nasopharyngeal neurological cancer.[17] The target for treatment is cyclin carcinoma xenografts in BALB/C nude.[30] E and cyclin D1, apoptosis (by activation of caspases 4. Selenium (Se): Se is an essential mineral and trace and downregulation of anti-apoptotic gene products), element for animals including humans. It has been survival (P13K/KAT pathway), angiogenesis (vascular shown to affect the functions of several specific endothelial growth factor), metastasis (CXC chemokine intracellular selenoproteins by being a compound of receptor 4), invasion (matrix metalloproteinase-9 and their essential constituents selenocysteine (SeCys) adhesion molecules), and inflammation (nf-kappa B, (Zeng and Combs 2008).[23] Both organic (Seleno tumor necrosis factor, interleukin-1, cyclooxygenase-2, amino acids) and inorganic (e.g., selenite and selenate) [18] and 5-lipoxygenase). form of Se shown impressive cancer chemopreventive effects in animals and human models (Woo et al.). Se Metals and minerals having Anticancer Property has antioxidant property, inhibition of tumor growth and inverse epidemiological correlation with cancer. Lee et 1. Vanadium: The compounds have insulin-like action,[19] al. reported the inhibition of LNCaP human prostate and it reduces hypertension and hyperglycemia. cancer xenograft by monomethalate Se. Selenium is an Antiproliferative effect of vanadium compounds important mineral, which is found in food in nutritional on malignant cell and normal cell lines appear to doses, it is also an essential component of SeCys in be exerted through mainly cell cycle arrest. Zhang selenoproteins, it prevents cell death and also promotes et al. demonstrated that vanadate induced G2/M-phase cell cycle progression. However, at higher doses that are arrest in p53-deficient mouse embryo fibroblasts and greater than the nutritional requirement but not toxic, Se promoted S-phase entry in the corresponding p53 induces apoptosis and cell cycle (Zeng, 2009). wild-type cells.[20] Oxidation state of vanadium can 5. Germanium: It has antioxidants properties which have also be determine various vanadium biological effect been shown to protect against cancer. It is an element of vanadium compounds; for instance, the activation which is found in some plant-based foods. Inorganic of intracellular signal transduction pathways which in and organic both germanium have been sold as dietary turn regulate cytosolic protein tyrosine kinases.[21] With supplements, recently the organic form of germanium the help of X-ray energy fluorescence, concentration of most commonly. Germanium is a constituent of many vanadium can be estimated.[22] medicinal plants such as ginger, garlic, and ginseng root 2. Magnesium: It is essential for good health, and it is fourth and it plays an important role in the pharmacological most abundant mineral in human body. 50% magnesium effects of the plants (Lu, 1998). It is also reported that found in bones and other half is found in inside the cell many organogermanium compounds can inhibit tumor of body tissue and organs. Magnesium deficiency results and metastatic growth and modify immune response in metabolic abnormalities and clinical consequences by inducing interferon-gamma (IFN-γ), increasing even cancer development. High dietary magnesium peritoneal macrophage activity, and enhancing NK cell [23] may decrease risk of CRC cancer. Over 300 enzymes activity (Aso et al. 1985 and suzuki 1985 and Kuwabara and ion transportation require magnesium for its role et al.,2002 and Kaplan et al.2004). in fatty acid and phospholipid metabolism which affects permeability and the stability of the membrane. Magnesium deficiency seems to be carcinogenic, and Animal Model for Cancer in case of a solid tumor, high level of supplemented magnesium inhibits carcinogenesis. 1. Spontaneous tumor models.[31] 3. Arsenic-arsenic is a natural compound, and it is used 2. Virus-induced tumor models.[31] in China for medical treatment about more than 25 a. Friend leukemia b. Rous sarcoma. centuries. Arsenic trioxide (Ar2SO3) has been used in patients having acute promyelocytic leukemia.[24] 3. Radiation-induced tumor models. Arsenic trioxide is safe not only in leukemia patients a. UV induced skin tumorigenesis in SKH-1 hairless but also in patients having many other malignancies. mouse[32]

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b. Two-stage models for skin tumorigenesis.[33] 8. Somkumar AP. Study on Anticancer Effects of Ocimum 4. Chemically induced tumor models[34] santum and Withania somnifera on Experimentally a. DMBA induced mammary tumors Induced Cancer in Mice. PhD Thesis. Jabalpur: b. DMAB (3, 2-dimethyl-4-aminobiphenyl) induced Jawaharlal Nehru Krishi Vishwa Vidyalaya; 2003. colon tumors 9. Meyer JJ, Taylor MB. Engelbrecht L. Inhibition c. 3, 4, 9, and 10 dibenzopyrene induced fibrosarcoma of herpes simplex virus type-1 by aqueous in mice extracts from shoots of Helichrysum aureonitens 5. Transplantable tumors:[35] (Asteraceae). J Ethnopharmacol 1996;52:41-3. • Methods of transplantation 10. Madhuri S, Pandey G. Some dietary agricultural plants i. Heterotopic transplantation with anticancer properties. Plant Arch 2008;8:13-6. ii. Orthotopic transplantation. 11. Madhuri S, Pandey G. Some anticancer from medicinal • Depending on host used plants of foreign origin. Curr Sci 2009;96:779-83. i. Syngenic models 12. Balachandran P, Govindaranjan R. Cancer an ayurvedic ii. Xenogenic models. perspective. Pharmacol Res 2005;5:19-30. 6. Genetically engineered mice 13. Poornima P, Efferth T. Medicinal and Aromatic Plants, i. Transgenic animals Ayurveda for Cancer Treatment. Med Aromat Plants ii. Knockout animals. (Los Angel) 2015;5:e178. 14. Available from: https://www.cancer.gov/about-cancer/ CONCLUSION treatment. [Last accessed on 2018 Feb 16]. 15. Roy A, Ahuja S, Bhardvaj N. A Review on medicinal Ayurveda is the ancient system of medicine having various plants against cancer. J Plant Sci Agric Res 2008;1:6. effects in diseases but research of Ayurvedic drugs is in 16. Roy A, Kundu K, Saxena G, Kumar L, Bhardvaja N. preclinical stage, and the basic principles are valid until today. Effect of different media and growth hormones on Current modern therapies cause various toxic side effects shoot multiplication of in-vitro grown Centella asiatica to the patient. For this reason, draw the global attention accessions. Adv Tech Biol Med 2016;4:12. toward herbal medicines. It is also known to everyone 17. Kainsa S, Kumar P, Rani P. Medicinal plants of Asian that western medicines provide symptomatic treatment origin having anticancer potential: Short Review. Asian J which does not look about the underlying conditions but Biomed Pharm Sci 2012;2:1-7. in ayurvedic treatment treats the diseases from the root of 18. Hyunsungl C. Curcumin inhibits hypoxia inducible origin. The ayurvedic researchers and practitioners improve factor-1 by degrading aryl hydrocarbon receptor nuclear the medicines by increasing their contribution. In this study, translocator, a mechanisum of tumor growth inhibitor. we discuss about the plants, metals, and minerals having the Mol Pharm (American Society for Pharmacology and anticancer property and also discuss about the models used Experimental Therapeutics) 2006;70:1664-71. for anticancer property. Ayurveda concepts have not yet been 19. Tsiani E, Fardel O. Vanadium compounds. Biological sufficiently validated; hence, the collaborations between actions and potential as pharmacological agents. Trends these two medicinal systems are mutually beneficial. Endocrinol Metab 1997;8:51-8. 20. Zhang Z, Chen F, Huang C, Shi X. Vanadate induces G2/M phase arrest in p53-deficient mouse REFERENCES embryo fibroblasts. J Environ Pathol Toxicol Oncol 2002;21:223-31. 1. Meena GC, Sharma LN, Purvia RP, Sharma N. Anticancer 21. Krejsa CM, Nadler SG, Esselstyn JM, Kavanagh activity of common herbs in ayurvedic perspective. Int TJ, Ledbetter JA, Schieven GL. Role of oxidative Ayurvedic Med J 2017;5:1659-69. stress in the action of vanadium phosphotyrosine 2. Madhurians S, Pandey G. Some anticancer medicinal phosphatase inhibitors. Redox independent activation of plants of foreign origin. Curr Sci 2009;96:779-83. NF-kappaB. J Biol Chem 1997;272:1154111549. 3. Polu P, Nayanabhirama U, Khan S. Herbal medicinal 22. Rizk SL, Sky-Peck HH. Comparison between plants as an anticancer agents. Ann Phytomed concentrations of trace elements in normal and neoplastic 2015;4:37-45. human breast tissue. Cancer Res 1984;44:5390-4. 4. Kaur R, Singh J, Singh G, Kaur H.Anticancer plant: 23. Singh M, Kumar D, Singh G, Sharma D, Swami G. A Review. J Nat Prod Plant Resour 2011;1:134-6. Natural minerals and cancer. J Appl Pharm Sci 5. Akerele O. Medicinal plants and primary health care: An 2013;4:45-8. agenda for action. Fitotrepia 1988;59:355-63. 23. Desoize B. Metals and Metal Compounds in Cancer 6. Ames BN, Gold LS. The cause and prevention pf cancer. Treatment. Anticancer Res 2004;24:1529-44. Proc Natl Acad Sci USA 1995;92:5258-65. 24. Feng CQ, Ma WL, Zheng WL. Research advances 7. Sravanthi V, Mayure VK, Finny GJ, Meher CP. Anti- on effect of arsenic trioxide on tumor. Ai Zheng cancer(Novel Agent):A Review; Pharmatutor-art-2222. 2002;21:1386-9. PharmaTutor 2014;2;119-53. 25. Liu Q, Hilsenbeck S, Gazitt Y. Arsenic trioxide-induced

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apoptosis in myeloma cells: p53-dependent G1 or G2/M 30. Connors TA, Roe FJ. Antitumor agents. In: Laurence DR, cell cycle arrest, activation of caspase 8 or caspase 9 and editor. Evaluation of Drug Activities: Pharmacometrics. synergy with APO2/TRAIL. Blood 2003;101:4078-87. Vol. 02. London: Academic Press; 1964. p. 627-70. 26. Hyun PW, Hee CY, Won JC, Oh PJ, Kim K, Hyuck IY, 31. Hong JT, Kim EJ, Ahn KS, Jung KM, Yun YP, Park YK, et al. Arsenic trioxide inhibits the growth of A498 renal Lee SH. Inhibitory effect of glycolic acid on UV-induced cell carcinoma cells via cell cycle arrest or apoptosis. skin tumorigenesis in SKH-1 hairless mice and its Biochem Biophys Res Commun 2003;300:230-5. mechanism of action. Mol Carcinog 2001;31:152160. 27. Shen ZY, Shen WY, Chen MH, Shen J, Zeng Y. 32. Hala UG, Yamout SZ, Sidani M. Tannins protect against Reactive oxygen species and antioxidants in apoptosis skin tumor promotion induced by UVB radiation in of esophageal cancer cells induced by As2O3. Int J Mol hairless mice. Nutr Cancer 2000;37:73-7. Med 2003;11:479-84. 33. Homburger F, Russfield AB, Baker JR, Tragier A. 28. Shi Y, Liu Y, Huo J, Gao G. Arsenic trioxide induced Experimental chemotherapy in chemically induced apoptosis and expression of p53 and bcl-2 genes in mouse tumors and their transplants. Cancer Res human small cell lung cancer cells. Zhonghua Jie He He 1962;22:368-75. Hu Xi Za Zhi 2002;25:665-6. 35. Navale AM, Chavan A. Animal models of cancer: 29. Du CW, Li DR, Lin YC, Wu MY. Arsenic trioxide A review. Int J Pharm Sci Res 2013;4:19-28. induces differentiation of human nasopharyngeal carcinoma in BALB/C nude mice xenograft model. Ai Zheng 2003;22:21-5. Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S204 A review on medicinal plants described in Ayurvedic classics having antidiarrheal and antidysenteric activity

Suranjana Dana1, Ambrish Kumar Singh2, Ashwini Kumar Kushwaha3 1Department of Ayurvedic Pharmacy, Rajiv Gandhi South Campus, Banaras Hindu University, Mirzapur, Uttar Pradesh, India, 2Department of Pharmacology, Faculty of Ayurveda, Rajiv Gandhi South Campus, Institute of Medical Sciences, Banaras Hindu University, Mirzapur, Uttar Pradesh, India, 3Department of Dravyaguna, Faculty of Ayurveda, Rajiv Gandhi South Campus, Institute of Medical Sciences, Banaras Hindu University, Mirzapur, Uttar Pradesh, India

REVIEW ARTICLE REVIEW Abstract

Diarrhea and dysentery are the most common disease among people of various age. Morbidity and mortality also occur. The diarrhea occurs from unhygienic environment, unsafe drinking water, and food poisoning and sometimes caused by pathogen. Dysentery is caused by excess intake of spicy, salty, and oily food material and also related with human pathogen Escherichia coli. In Ayurvedic classics, diarrhea and dysentery are correlated with Atisara and Pravahika, respectively. The popularity of herbal medicine is increasing day by day in global market. This paper review shows the efficacy of the plants describing for various related activities.

Keywords: Atisara, Ayurveda, diarrhea, dysentery, medicinal plants, pravahika

INTRODUCTION diarrhea is two types which are acute watery diarrhea (dehydration of water) caused by E. coli and another is iarrhea is one of the most common bloody diarrhea caused by Shigella.[6] health problems in developing countries Dthat occur in all groups, and sometimes, it causes death in rural area as well as urban AYURVEDIC VIEW OF DIARRHEA AND area. The mortality of death is vast in rural area DYSENTERY than urban area for their unawareness about health and disease.[1] Diarrhea is the third most In Ayurveda, diarrhea is compared with Atisaara, it is common cause of death in children, liable for condition where repeated passing of excessively watery stool 13% of deaths an every year.[2] Poor sanitation is with frequent bowel movements due to indigestion (ajeerna) an important factor and most common problem or lack of digestive fire (agnimandya). Dysentery is correlated for diarrheal disorder and mainly found in with Pravahika and it is occur due to vitiated Kapha and Vata rural.[3] The second common cause of the dosha, where Kapha get aggravated in stomach and pulled problem is lack of safe drinking water.[4] Mainly down by vitiated Vata dosha into intestines. As a result, stool Shigella bacteria is responsible for bacillary becomes sticky, thus body requires an additional effort for dysentery and transmitted by oral route and elimination of such stool. amoebic dysentery caused by Escherichia coli which transmitted through water.[5] Address for correspondence: Ashwini Kumar Kushwaha, Department of Dravyaguna, Faculty of Ayurveda, Rajiv Gandhi South Campus, TYPES OF DYSENTERY AND Institute of Medical Sciences, Banaras Hindu University, DIARRHEA Mirzapur, Uttar Pradesh, India. E-mail: [email protected] Commonly dysentery are two types: One is Received: 13-01-2018 amoebic dysentery which caused by Entamoeba Revised: 19-02-2018 histolytica (protozoa) and another is Bacillary Accepted: 27-02-2018 dysentery caused by Bacillus subtilis. Similarly,

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TYPES OF ATISAAR (DIARRHEA) AN Raktaja, Shokaja, and Bhyajawhere as depending on which PRAVAHIKA (DYSENTERY) IN AYURVEDA particular Dosha is vitiated, and Pravahika (dysentery) has Depending on the etiology, there are seven types of diarrhea, been classified into Vataj, Pittaj, Kaphaj, and Raktaj types in namely, Vataja, Pittaja diarrhea, Kaphaja, Tridoshaja, Ayurveda.

List of some common plants found in india having antidiarrheal and antidysenteric activity Botanical name Family Chemical Pharmacological action constituent Papaver somniferum (L.) Papaveraceae Morphine Non‑narcotic part of ahiphena is used Codein[7] in back pain in diarrheal condition, and it gives relief from internal hemorrhage which occurs in dysenteric condition[8] Trachyspermum ammi (L.) Umbelliferae Thymol, carvacrol, Aqueous extract of ajwain is having dipentene[7] hepatoprotective activity and gives a very good result in diarrhea[9] Tamarindus indica (L.) Fabaceae Carbohydrate, The tannic acid gives a good response phosphorus[7] in diarrhea and dysentery[10] Alangium salvifolium (L.) Cornaceae Cephaline, emetine[7] The stem and bark paste give relief in diarrhea and dysenteric condition[11] Ailanthus excels Roxb. Bignoniaceae Vitexin[7] The stem bark of this plant having anti‑amoebic activity and used in bloody diarrhea[12] Terminalia arjuna (L.) Combritaceae Arjunetine, tannin[7] The bark of this plant has antidysenteric property[13] Anthocephalus indicus Miq Rubiaceae Tannic acid[7] The fruit having antimicrobial activity which inhibits growth of pathogen E. coli. [14] The extract of flower reduces fecal dropping in diarrheal condition [15] Mangifera indica (L.) Anacardiaceae Flavonoid, The seed kernel of mango plant having triterpenoid, antidiarrheal activity, and it reduces mangiferin, tannic internal hemorrhage and also relieves acid[7] from dysentery[16] Psoralea corylifolia (L.) Fabaceae Alkaloid, resin, Leaves having antidiarrheal property essential oil[17] which reduce intestinal motility.[18] Psidium guajava L. Myrtaceae Catechin, Bark decoction is used in diarrheal epicatechin, rutin, condition, and leaf and shoot juice sesquiterpene[19] also inhibit gastric secretion and reduce intestinal motility and capillary permeability[20] Garcinia pedunculata Guttiferae Riboflavin, thiamine, The fruit and leaf having properties gallic acid minerals[21] which reduce gastric empty time and relief from internal hemorrhage in diarrheal and dysenteric condition[22] Aegle marmelos Corr. Rutaceae Tannin, pectin, The fruit of this plant inhibits marmeline, aegelin[7] prostaglandin synthesis and significantly reduces and stops intestinal movement or motility and gives quick relief from diarrhea and dysenteric condition[23] The root parts are also used for treatment of dysentery[24] Acacia arabica Willd. Fabaceae Tannin[7] The pod of this plant having antidiarrheal and antidysenteric properties.[25] (Contd)

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List of some common plants found in india having antidiarrheal and antidysenteric activity Botanical name Family Chemical Pharmacological action constituent Acacia nilotica Mimosaceae Minerals, protein[26] Pods and tender leaves having antidiarrheal property[27] Sida cordifolia (L.) Malvaceae Palmitic acid, The root of this plant having good ephedrine, antimicrobial property and fight against pseudoephidrine, pathogen Staphylococcus aureus which indole alkaloid[28] sometimes occurs in diarrheal condition and relief from this disease[29] Cannabis sativa (L.) Cannabinaceae Cannabinol, Cannabis gives relief in inflammatory tetrahydrocannabinol, bowel disease and abdominal pain cannabidiolic acid[7] which occurs in diarrheal condition. and by the way, it relieves from diarrhea[30] Terminalia bellerica Roxb. Combritaceae Tannin, chebulinic The plant inhibits gastric secretion and acid, chebulagic reduce gastric emptying time[31] acid[7] Eclipta alba Hassk. Asteraceae Alkaloid, flavonoid, Whole plant is used in dysentery[33] volatile oil[32] Ziziphus jujuba Rhamnaceae Alkaloidmauritine‑A, Aqueous extract of Ziziphus jujube mucronine‑D, reduced intestinal motility and inhibit amphibine‑H, gastric emptying time, and it is flavonoid[34] responsible for constituent tannin present in it which having antidiarrheal activity[35] Oxalis corniculata (L.) Oxalidaceae Alkaloid, flavonoid, The plant fights against pathogen like glycoside, tannin.[36] Entamoeba‑histolytica and kills the pathogen Giardia lamblia which is the main cause of diarrhea and dysentery[37] Acalypha hispida Euphorbiaceae Alkaloid, flavonoid, The root extract of this plant having carbohydrate[38] cooling property which gives relief from abdominal pain, occurs in diarrhea and also contains tannins and flavonoids which give antidiarrheal activity[38] Punica granatum (L.) Punicaceae Tannin, alkaloid, Decoction of the leaf having antidiarrheal flavonoid, asiatic effect due to the presence of tannin[40‑41] acid[39] Coriandrum sativum (L.) Apiaceae Tannin, flavonoid, The extract is having antidiarrheal alkaloid[42] property by reducing intestinal motility[42] Santalum album (L.) Santalaceae Santalol, volatile oil[7] The methanol extract of this plant having antidiarrheal property which reduces intestinal motility which occurs in diarrhea[43] Xanthium indicum Asteraceae Alkaloid[7] The plant is having antidiarrheal property[44] Woodfordia fruticosa Kurz. Lythraceae Tannin, lawsone[7] The flower of this plant having antiamoebic activity and fight against round warm. And used in diarrhea and dysentery[45] Fagonia cretica (L.) Zygophyllaceae Flavonoid, alkaloid, The infusion of leaves having cooling protein[46] property and give relief from diarrheal condition[47] Berberis aristata Berberidaceae Barberini, berbamine, The plant gives antidiarrheal effect aromoline, karachine, which inhibits intestinal secretion and palmatine[48] increases absorption and reduces removing of fecal matter and relief from diarrhea[49] (Contd)

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List of some common plants found in india having antidiarrheal and antidysenteric activity Botanical name Family Chemical Pharmacological action constituent Euphorbia thymifolia (L.) Euphorbiaceae Sterols, minerals, The plant having antibacterial activity antioxidants, and fight against bacteria, E. coli and cinnamic acid inhibit their growth and give relief from glycoside, essential dysentery[51] oil tannin[50] Scindapsus officinalis Araceae Flavonoid, terpenoid, Fruit of this plant having activity steroid[52] against pathogen E. coli and relief from dysentery[52] Syzygium cumini (L.) Myrtaceae Tannin, protein, The plant having antidiarrheal property carbohydrate, and it inhibits gastric secretion and mineral[7] increases absorption, reduces intestinal motility and gastric emptying time, and relieves from diarrhea[53] Terminalia chebula Retz. Combretaceae Chebulenic acid, Fruit of this plant having laxative property chebulagic acid, which reduces intestinal motility and tannin[7] increases the stomach emptying time and by this way, relieves from diarrhea[54] Valeriana hardwickii Wall. Valerianaceae Valerianic acid[7] The rhizome of this plant inhibits intestinal motility or bowel contraction and relieves from diarrhea[55] Myristica fragrans Houtt. Myristicaceae Glycoside, eugenol[56] A study shows that anti nutmeg oil having antidiarrheal effect which reduces number of faces in rats. Iwu (1993)[57] Holarrhenaantidysentrica Apocynaceae Triterpenoid, alkaloid. The seed having antidiarrheal activity. It (L.) Stigmasterol, lupeol, fights against pathogen E. coli and relief wrightial[58] from diarrhea[59] Raphanus sativus (L.) Brassicaceae Oleic, linoleic, The extract R. sativus of shows a strong palmitic acid[60] antibacterial activity and it inhibits the growth of E. coli which is a intestinal flora, and by the way, it gives relief from dysentery. the juice also having these property[61] Butea monosperma (L.) Fabaceae Triterpene, butin, The flower of this plant having flavonoids[62] antidiarrheal activity and it reduces intestinal motility[63] Trichosanthes dioica Roxb. Cucurbitaceae Tannin, vit‑A, vit‑C, Water extract of this plant having flavonoid[64] antidiarrheal property which reduces excretion of watery stool and inhibits secretion and gastric motility reduce. The plant also contains flavonoid containing compound which mainly responsible for it[65] Cissampelos pareira (L.) Menispermaceae Alkaloid hyatidine[66] Root of this plant having antidiarrheal property, and it reduces gastric emptying time[67] Oroxylum indicum Vent. Bignoniaceae Ellagic acid, The whole part of plant used in diarrhea oroxyline, chrysin, and dysentery[69] baicalein [68] E. coli: Escherichia coli

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List of ayurvedic medicinal plants with antidiarrheal and antidysenteric activity Classical name Part use Action Ahiphena Seed Ahiphena mixed with bark of kupilu, taken with honey[70] Ajmoda Fruit Ajomoda, aralu, and madhuka mixed with milk and administered with honey. It gives relief in diarrhea related with abdominal pain[71] Chincha Seed Amlika seed, sunthi, rock salt, and ajwain mixed and taken with anupan. It gives an efficacious result very quickly in diarrheal condition[72] Ankolah Root bark, stem Root bark is taken with buffalos buttermilk and it is very efficacious in diarrhea[73] Aralu Stem bark Bark of aralu spread over with ghee, apply heat, and administered with honey which give relief from diarrhea[74] Arjuna Stem bark Arjun bark is administered with honey and taken with milk, very efficacious in bloody diarrhea[75] Kadamba Fruit and bark Kwath of bark used in rakta‑atisara[70] Amra Seed kernal Decoction of bilva mixed with seed kernel of amra and taken with honey and sugar for vomiting and diarrhea[76] Bavchi Leaves Cooked leaves of the plant administered with curd daily in dysenteric condition[77] Amratafalam Leaves The leaf juice of guava mixed with pomegranate juice and administered in diarrheal condition[78] Amlavetasa Fruit and leaves At first, fruit is dried in sunlight, then soaked into water and used in dysentery[78] Babool Pods Babbularistha is administered in diarrheal condition[79] Babool (vilayati) Pods and leaves Fruit is administered in diarrheal. Powder of bark is used in dysenteric condition[80] Bala Root Bala is cooked with milk, administered with sunthi and juggery[81] Bhang Leaves Bhang and jatiphal mixed with each other and administered with indrayava[13] Bibhitaki Fruit Fruit of bibhiitaki with salt is used in diarrheal condition[82] Bhringaraja Whole plant Root of Elipta alba is taken with water[83] Bilwa Fruit The fruit of this plant administered with madhu in atisara[84] Changery Leaves Changery and dugdhika mixed with dadim seed, administered with curd, ghee, etc[85] Dadima Bark Bark of kutaja and dadima mixed with honey and give relief from bloody diarrhea[86] Dhanyaka Fruit Decoction of dhanayak is powerful digestive and act against diarrhea[13] Chandan Heartwood Chandan is taken with rice water in diarrheal condition. It gives a cooling effect and give relief from pain[87] Kamal Whole plant Part of the plant taken with lajjalu and administered with honey and milk[88] Chameleon Whole plant Decoction of whole plant used in dysentery[5] plant (Jati ) Dhataki Flower Dhatyakadichurnais administered with badari, kapittha, and honey and used in atisara[89] Durlabha Root Durlabh is administered with curd in diarrhea[13] Daruharidra Rhizome Decoction of rhizome is used in diarrhea[90] Dugdhika Whole part Whole plant used in diarrhea[90] Gajapippali Fruit It is administered in bloody diarrhea[90] Jambu Seed Seed of jambu is very beneficial in diarrhea and dysentery and administered with jaggery. Sometimes, decoction of bark used in diarrhea and dysentery[91] Haritaki Fruit Decoction of fruit powder of this plant administered in dysenteric condition[92] Jatiphala Fruit The paste of jatiphal mixed with sunthi and pounded with cold water relief from diarrhea[93] Kutaja Bark Decoction of stem bark with seed and musta taken with sugar, honey and used in diarrheal condition[94] Mulaka Root The seed of this plant used in diarrhea[61] (Contd)

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Palash Flower The flower of kimshook administered in diarrhea[95] Parwal Leaves Leaf of parwal administered with powder of marich[96] Patha Root Churna is taken with hingu, ajomoda, and saindhavlavana and relieves from diarrhea[97] Shyonaka Whole part Kwath of root is used in diarrhea and dysentery[98]

CONCLUSION Alangium salvifolium. J Chem Pharm 2014;6:611-8. 12. Kumar D, Bhat ZA, Singh P, Shah MY, Bhujbal SS. Diarrhea and dysentery are a one of the common health Ailanthus excels Roxb. is really a plant of heaven. Indian problems in rural and urban areas of all age grouped peoples, J Pharmacol 2010;6:535-50. and it is mainly due to unawareness about environment, use of 13. Gairola S, Sharma J, Gaur RD, Siddiqi TO, Painuli RM. unsafe drinking water, use of poor sanitation, and bad hygienic Plants used for treatment of dysentery and diarrhoea by practice. Sometimes, this disease also related with poor the Bhoxa community of district Dehradun, Uttarakhand, nutrition and food poisoning. Various plants have been reported India. J Ethnopharmacol 2013;15:989-1006. for having antidiarrheal and antidysenteric activity which is 14. Mishra RM, Siddque L. Antibacterial properties of traditionally used in Indian system of medicine for a long time. Anthocephalus cadamba fruits. AJPSKY 2011;1:1-7. The plants listed above have shown related activity in clinical 15. Dwevedi A, Sharma K, Sharma YK. Cadamba: and experimental study, and the active principles of some plants A miraculous tree having enormous pharmacological are also identified for antidiarrheal and antidysenteric activity. implications. Pharmacogn Rev 2015;9:107-13. 16. Shah KA, Patel MB, Parmar PK. Mangifera indica. Pharmacogn Rev 2010;4:42-8. 17. Khushboo PS, Jadhav VM, Sathe NS. Psoralea REFERENCES corylifolia Linn. Kushtanashini. Pharmacogn Rev 2010;4;69-76. 1. Tikadar P, Palita SK, Panda D. Phytochemical analysis 18. Chishty S, Monika B. A review on medicinal importance of medicinal plants used for treatment of dysentery and of Babchi (Psoralea corilifolia). IJRSR 2016;7:11504-12. diarrhoea by the Paraja Tribe of Koraput, Odisha, India. 19. Wang F, Chen YH, Zhang YJ, Deng GF, Zou ZF, Li AN, Int J Herb Med 2017;5:14. et al. Chemical components and bioactivities of Psidium 2. Abbas J, Pandey DC, Verma A, Kumar V. Management guajava. Int J Food Nutr Saf 2014;5:98-14. of acute diarrhea in children: Is the treatment guidelines 20. Sanda KA, Grema HA, Geidom YA, Buker YM. is really implemented? Int J Res Med Sci 2018;6:539-44. Pharmacological aspect of Psidium guajava. Int J 3. Hazarika MP. Sanitation and Its Impact on Health. Int J Pharmacogn 2011;7:316-24. Sci Res Publ 2015;5:1-11. 21. Islam MZ, Hoque MM, Asif SM, Alam UI, Monalisa K. 4. Myint SL, Myint T, Aung WW, Wai KT. Prevalence of Chemical composition, antioxidant capacities and household drinking water contamination and of acute storage stability of Citrus macroptera and Garcinia diarrhoeal illness in a Periurban community in Myanmar, pedunculata Fruits. Emir J Food Agric 2015;27:275-82. WHO. South East Asia J Public Health 2015;4:62-68. 22. Gogei G, Das AK. Ethanomedico botany and 5. Dans L, Martinez E. Amoebic dysentery. Clin Evid phytochemical screening of Garcinia pedunculata 2007;1:1-7. Roxb ex Buch-Ham from Arunachal Pradesh, India. 6. Kar A, Borthakur SK. Medicinal plants used against J Bioresour 2016;3:1-8. dysentery, diarrhea and cholera by the tribes of erstwhile 23. Rao GH, Lakshmi P. Evaluation of antidiarrhoeal activity Kameng district of Arunachal Pradesh. Nat Prod of extract from leaves of Aeglemarmelos. J Appl Pharma Radiance 2008;7:176-81. Sci 2012;2:75-8. 7. Sharma PV. Dravyaguna-Vijnana. Varanasi; Chukhambha 24. Johnson M. Biochemical variation studies in Aegle Visvabharati, Oriental Publishers and Distributors; 2006. p. 2. marmelos (L.) Corr - A medicinally important plant. 8. Patel S. A critical review on upavisa with special J Chem Pharm Res 2010;2:454-62. reference to their therapeutics. JBSO 2014;2:196-02. 25. Farzana MU. A review of ethno medicine, phytochemical 9. Chahal KK, Dhajwal K, Kumar A, Kataria D, Singla N. and pharmacological activities of Acacia nilotica (Linn) Chemical composition of Trachyspermum ammi and Willd. J Pharmacogn Phytochem 2014;3:84-90. its biological properties. J Pharmacogn Phytochem 26. Abbasian K, Asgarpanah J, Ziarati P. Chemical 2017;6:131-40. composition profile of Acacia nilotica Seed growing 10. Khanjada SK, Shaikh W, Sofia S, Kazi TG, wild in South of Iran. Orient J Chem 2015;2:1027-33. Usmanghani K, Kabir A, et al. Chemical constituents of 27. Ali A. Acacia nilotica: A plant of multipurpose medicinal Tamarandus indica medicinal plants in Sindh. Pak J Bot uses. J Med Plant Res 2012;6:1492-6. 2008;40:2553-9. 28. Jain A, Choubey S, Singour PK, Rajak H, Pawar RS. 11. Singh B, Vijayvergia R. Biological evaluation of Sida cordifolia (Linn) - An overview. J Appl Pharma Sci

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International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S212 Current and future perspectives of Ayurveda and Yoga for management of Prameha

Sushil Kumar Dubey1, Ramesh Kant Dubey2 1Department of Kriya Sharir, Faculty of Ayurveda, I.M.S. BHU, Varanasi, Uttar Pradesh, India, 2Department of Swastha Vritta, Government Ayurvedic College & Hospital, Atarra (Banda), Uttar Pradesh, India

Abstract

Ayurveda and Yoga are the ancient most systems of holistic approaches to healing of suffering humanities.

REVIEW ARTICLE REVIEW Ayurveda is based on Tridosh theory of diseases wherein Ahar (diet), Vihar (lifestyle), and Aushadh (drug) have been advised for alleviation of diseases with a primary focus on the body along with mind while the approach of Yoga is directed more toward control of mind through its eight limb path. The clinical features of passage of excessive quantity of urine resembling honey in taste and color along with sweetness of the whole body of Madhumeha and the Vatika variety of Prameha are nearly equivalent to that of diabetes mellitus which is a chronic metabolic disorder of carbohydrate, protein, and fat caused by absolute or relative deficiency of insulin. Prameha is characterized by Prabhutavil - Mutrata, i.e., passage of excessive and turbid urine with increased frequency. There are 20 types of Prameha described in Ayurvedic texts, and Madhumeha is one of the Vatika varieties of Prameha which has been considered in Asadhya/Yapya category. All the types of Prameha, if untreated for longer duration get converted to Madhumeha, hence become incurable/Yapya. Ayurveda advocates specific lifestyle and dietary habits from early life. These lifestyle measures can prevent Prameha in its primordial stage and also help in the management. Various Yogic postures have also been found effective in preventing and treating Prameha. This paper will deal in length of the current and future perspectives of Ayurveda and Yoga for management of Prameha.

Key words: Ahar, diabetes mellitus, Madhumeha, Prameha, Vihar, Yoga

INTRODUCTION obesity. Integration of the theory and therapeutic measures of Ayurveda in the management of these disorders may prove to rameha is one of the chronic diseases be beneficial. Prameha is a Tridoshaja Vyadhi that involves having 20 types enumerated in Ayurvedic all the three functional units with a predominance of Kapha. classical texts, and Madhumeha is Prabhutavil –Mutrata,[7] i.e., passage of excessive and turbid P urine is the characteristic feature of Prameha. There are 20 considered under vataja category. It is the incurable/Yapya and advanced stage of prameha[1] types of Prameha resulting from the interaction of the three characterized by excretion of urine which Doshas (Vata, Pitta, and Kapha) and 10 Dushyas (disturbed resembles honey in taste and characteristics functioning of the principles that support the various bodily and also accompanied by sweetness of tissues), namely, meda (fat), mansa (muscle), kleda (water whole body of the patient.[2] Prameha is contents), shukra (semen regulating factors and hormones), an anusangi roga (adherent disease)[3] and shonita (blood), rasa (plasma), vasa (fat content of muscles), santarpanajanya (caused by over nutrition) majja (bone marrow), lasika (lymph), and oja (immunity roga (disease) caused by saturation of body due regulating factors); many of these subtypes have sweet urine, to overeating.[4] Due to difficulty in treatment, whereas some of them have different coloration of the urine.[8] seriousness, and complications, prameha has It is notable that 20 types of Prameha in fact do not refer to 20 been mentioned as one of eight Maharogas (Major diseases).[5] In Sushruta Samhita, Address for correspondence: Madhumeha has been described as “Medo Dr. Sushil Kumar Dubey, Department of Kriya dushtijanya vikara (disorder of fat/lipid).[6]” Sharir, Faculty of Ayurveda, I.M.S. BHU, Varanasi, Uttar Pradesh, India. Phone: 9415540732. Prameha includes clinical conditions involving E-mail: [email protected] pre-diabetes, diabetes mellitus (DM), and

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S213 Dubey and Dubey: Role of Ayurveda and Yoga in Management of Prameha types of diabetes, but these represent to 20 types of physical Madhumeha which is a type of Vatika Prameha.[17] Depending abnormalities of urine which may be found in different on hereditary and dietetic factors, the patients are classified patients with or without association of DM. This disease is as sahaja pramehi and apathyanimittaja pramehi.[18] closely related with Sthaulya (i.e., obesity). Sahaja and Jatah (hereditary) Pramehi can be correlated with Type I diabetes Prameha is a kulaja vikara, i.e., it has tendency of (IDDM), while Apathyanimittaja (acquired by faulty diet and inheritance.[19] Excessive intake of madhura rasa (sweet lifestyle) Prameha can be correlated with Type II diabetes substances) by mother during pregnancy can induce prameha (NIDDM). Madhumeha is a subtype of Vataja Prameha in the child.[20] Chakrapani has opined that the main cause that can occur as the terminal stage of Type II diabetes (in of defect in bija (spermatozoa or ovum) is apathya sevana which insulin is required) or as Type I diabetes beginning in (faulty diet and lifestyle) by the parents.[21] The specific early childhood. Various dietary, lifestyle, and psychological etiology of Madhumeha is depicted in Table 1. factors are involved in the etiology of Prameha, particularly in relation to disturbances in fat and carbohydrate metabolism. The following risk factors have been found associated with DM which also resemble with the most of the etiological The increasing stress during the work and rapid industrial factors mentioned in ayurvedic texts Table 2. growth, changing dietary habits and various types of foods such as preserved food items and fruits, excess amount of Kaphaja and pittaja prameha which are present since long soft drinks and beverages, and canned foods along with lack period may get anubandha of vata due to chronicity, i.e. they of exercise result into the disturbance of Agni or metabolism may be converted into vataja prameha - Madhumeha. and ultimately cause various chronic and non-communicable diseases. DM is one of these diseases whose current estimated Due to ksaya (diminution) of vital dhatus there is provocation number of cases is predicted to double by 2025. About 20% of of vata which causes excretion of urine resembling honey the current global diabetic population resides in the Southeast i.e., Madhumeha.[24,25] Asia region and the number of diabetic persons are likely to triple by the year 2025.[9] Excessive intake of unctuous substances, articles having acidic and salty taste, guru, snigha ahara (unctuous diet), and Although there is the availability of insulin and a large number indulgence in excessive sleep and sedentary habits lead to of oral hypoglycemic agents, none is an ideal for the treatment excessive increase of kapha, pitta, meda, and mamsa which of the majority of NIDDM patients; most individuals cannot be causes srotorodha (obstruction of channels) leading to avarana adequately controlled and secondary failure to oral treatment (covering) of vata. This vitiated vata carries the oja (vital is common feature as the disease progresses. Hence, there is a essence) to basti, resulting in Madhumeha and appearance need of finding better treatment option for DM. Ayurveda and of the symptoms of vata, pitta, and kapha alternately and Yoga may prove to be better alternatives or complementary to frequently.[22] the management of this rapidly rising disease.

Careful obeying the rules mentioned under Swastha Vritta Role of Ayurveda in Management of Prameha (preventive medicine and Hygiene) such as proper dietary habits, Dinacharya (day regimen), Ratricharya[10] (night There are two main goals of Ayurveda: (i) Protection of health regimen), Nidra[11] (sleep), Ritucharya[12] (seasonal regimen), and (ii) cure of disease of a patient.[25] Individual peculiarities Sadvritta[13] (good conduct), Achara Rasayana[14] (promotive such as Prakriti, Satmya, Sara, Samhanana, and so on are ethical practices), and use of Rasayana[15] (rejuvenation also considered.[26] therapy) are some of the measures which can prevent DM at all levels. Various Ayurvedic herbal and herbomineral Ahar is one of the three pillars of life, namely, (i) Ahar, i.e. proper preparations have been found to be effective in Prameha. diet, (ii) Nidra (i.e., proper sleep), and (iii) Brahmacharya, i.e., divine lifestyle and control of sexuality.[27] Specific rules Yoga originated in India over 4,000 years ago as a traditional form of mind–body training that seeks to unite the individual Table 1: Specific etiology of Madhumeha[22] self with the transcendental self. Several trials have shown that yogic practices such as asanas (postures) and pranayama Ahara Vihara (breath control) can reduce fasting blood glucose and Excessive intake of Excessive indulgence in glycosylated hemoglobin A1c, as well as improve the lipid Guru dravya Nidra [16] levels and quality of life of Type II DM patients. Snigdha dravya Asya sukha (indulgence in sitting) Amla dravya Tyakta vyayama Etiopathogenesis of Prameha Lavana rasa Tyakta chinta Nava anna Samsodhana akurvatam The causative factors of prameha, namely, sedentary habits and dietary factors in general are also applicable to Nava pana

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S214 Dubey and Dubey: Role of Ayurveda and Yoga in Management of Prameha for taking diet such as Ashtaharvidhi Visheshayatanani[28] and time having six Rasas.[36] For the purpose of taking food, and Dwadasha Ashanapravicharana[29] and also specific one part of stomach should be filled up with solid food, the regimens for regulating lifestyle such as Dinacharya,[10] second part with liquids, and the third part should be left for Ratricharya,[30] Ritucharya,[31] and Sadvritta[32] are special Vata, Pitta, and Kapha.[37] features of Ayurveda. A person whose lifestyle is based on these principles and is truthful, liberal, forgiving, and There are eight factors - Prakriti, Karana, Samyoga, Rashi, serves noble persons will never be sick.[33] For the purpose Desh, Kala, Upayoga Samstha, and Upayokta which of treatment, the patients suffering from Prameh have been determine the utility of food and are jointly responsible for classified as (1) Shtula and Balwan (obese and strong) and bringing about the requisite benefits.[38] (2) Krisha–Durbala (thin and weak) which resemble the modern principle of management of DM wherein diabetic patients have been classified as obese and non-obese. Sthula Role of Aushadh in Management of DM Pramehi are advised Sanshodhan while Krisha Pramehi are given Samshamana Therapy.[34] In Prameha/Madhumeha, drugs having rasayana, balya, and jivaniya action as well as pramehaghna properties such as Amalki, Guduci, Pippali, and Haridra have been found Role of Ahar in Management of Prameha effective and globally proven hypoglycemic agents. Such measures which reduce meda and kapha, for example, heavy Ahar has been called as Mahabhaishajya (the super most exercise, ruksa udavartana, and ratri jagarana are beneficial medicine) in the Kashyap Samhita.[35] Ojas, glow, geniousness, for patients of prameha.[39] and radiance all such qualities in the human beings develop from the only diet which is congenial, appropriate in quantity, Herbs and formulations used in Prameha/Madhumeha (DM) as per Ayurvedic texts are mentioned in Table 3. Table 2: Risk factors for DM[23] Non‑modifiable Modifiable Role of Vihar in Management of DM Age Sedentary lifestyle Male gender Diet Regular Vyayam (exercise) should be performed till the Family history of diabetes mellitus Malnutrition appearance of signs of proper Vyayam characterized by Genetic factors Alcohol appearance of perspiration, increased respiration, lightness of the organs, and feeling of obstruction in cardiac Obesity region.[40] Exercise conditions the skeletal muscles which ‑ Viral infections decreases oxygen consumption for the same workload.[41] ‑ Stress Stress can be reduced regulating daily regimen, proper exercise, DM: Diabetes mellitus and Yogic practices along with meditation.[42] Exercise reduces

Table 3: Certain preparations mentioned for prameha in different ayurvedic texts Preparations Example Svarasa Amrita, Dhatri (S. M.K.1), Satavari (Bha. Ra. 37) Kvatha Phalatrikadi Kvatha (C.Ci. 6), Vidangadi Kvatha (Yo. Ra) Churna Eladi Curna (Bha. Ra. 37) Karkatibijadi Curna (Yo. Ra.) Kalka Triphala Kalka (Yo. Ra. Gutika (Vati) Chandraprabha Vati (Sa. S. M. K.7), Candrakala Gutika (Bh. Ra. 37) Guggulu preparations Goksuradi Guggulu (Sa. M.K. 7) Modaka Trikatukadya Modaka (B.P.M.K. 38) Asava Lodhrasava (C.Ci. 6). Sarivadyasava (Bha. Ra. 38) Arishta Deodarvyadyarishta (Sa. M.K. 10) Ghrita Dhanvantara Ghrta (Ca. Da. 35), Dadimadya Ghrta (Bha.Ra. 37). Taila Haridradi Tail (Yo. Ra.) Paka Puga Paka (Yo. Ra.), Ashvagandha Paka (Y. Ra.) Rasa Aushadhi Basanta Kusumakara Rasa, Brhat Vangesvara Rasa, Svarna Vanga, Prameha Chintamani Rasa (Bha, Ra. 37) Others Guducyadi Yoga, Bhudatryadi Yoga, Nisha Triphala Yoga (Yo. Ra.), Silajita (S. Ci. 13)

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S215 Dubey and Dubey: Role of Ayurveda and Yoga in Management of Prameha the Meda, increases the digestive power, and maintains the may still be poor due to irreversible major impairments or compactness of the body tissues. Sushruta has recommended severe disabilities. It is most often treated with diet and exercise and diet for the management of poor and rich patients. exercise in conjunction with oral hyperglycemic drugs and Poor patients should move from one to the other village and insulin. Controlling the disease is the prime aim because earn his living by begging. Persons who eat Shyamaka and there is no cure and the complications are very critical and fruits of Amalaki, live along with animals, and break the hazardous. Oral hypoglycemic agents and insulin used for stones become free from Prameha within 1 year.[43] the treatment of DM by the allopathic system of medicine have numerous side effects. Ayurveda because of its holistic approach not only aims to achieve strict glycemic control but Role of Yoga in Management of DM also treat root cause of the disease. The term Yoga means to unite or to combine, and it may Ayurveda can provide better management for Madhumeha be taken to mean a state of union of the individual soul without hazardous side effects. Vagbhatta has classified or consciousness with the cosmic or supreme soul or Madhumeha into two categories,[26] namely, Dhatukshayajanya consciousness or a total integration of the physical, mental, Madhumeha and Avaranajanya Madhumeha. The factors intellectual, and spiritual aspects of the human personality.[44] which provoke Vata directly cause Apatarpanajanya Madhumeha and the factors which provoke Kapha and The ultimate goal of Yoga is not the treatment of diseases, Pitta cause Santarpanajanya Madhumeha. In the former Various diseases may get pacified in the course of following type, the patients are usually asthenic can be correlated with the path of Yoga to achieve its real goal of union of individual Type I DM, and in the latter type, patients are obese and consciousness with cosmic consciousness. There are eight can be equated with Type II DM. Under the Samprapti of limbs of Yoga, namely, Yama, Niyam, Asana, Pranayam, Santarpanajanya Madhumeha or in Sthula Madhumehi, the Pratyahar, Dharana, Dhyan, and Samadhi described by vitiated Kapha and Pitta obstruct the Path of Vata causing Patanjali.[45] its provocation. Understanding ayurvedic view of the etiopathogenesis of Madhumeha in integration with modern Yogic practices such as Pranayam, Paschimotanasa, science will help in developing proper dietary and lifestyle Dhanurasana, Bhujangasana, Halasana, Vajrasana, and modification in the form of Nidan parivarjana, i.e. avoiding Ardhamatsyendrasana in various studies have produced the causative risk factors and adopting beneficial dietary an increase in the lean body mass and decrease in the body habits and lifestyles because 50% of cases of DM respond fat percentage. This leads to an improvement in insulin well to diet and exercise regimens. sensitivity and reduction in insulin resistance. Insulin is the major abnormality in Type II diabetes and precedes the Modern medical science is materialistic having concern development of overt diabetes by several years. The reduction primarily with the body and drugs are the mainstay of its in free fatty acid levels also reduces the lipotoxicity, which management. On the other hand, Ayurveda being a holistic has now been shown to have a significant effect on beta system is concerned with the development of physical, cell function. Therefore, it is reasonable to postulate that mental as well as spiritual aspects. With the advancement of the beneficial effect of yogic asanas on the insulin kinetics the modern medicine, powerful drugs have conquered many and the lipid metabolism prevents the beta cell exhaustion infections and decimated epidemics. However, it primarily and the development of a beta-cell secretory defect, thereby depends on drugs which have many harmful side effects. It preventing the development of Type II diabetes.[46] does not have full answers for many chronic and degenerative diseases whose incidence is increasing rapidly. Many Future Perspectives of Ayurveda and Yoga in patients of chronic and non-communicable diseases such as Management of Prameha -Discussion DM and heart disease have to take life-long treatment using drugs that are not only expensive but have many undesirable There is a lot of stress and strain in the present era due side effects. In such situation, the only option that remains to modifications in lifestyle, change in dietary habits, is the primordial and primary prevention of chronic and urbanization, and industrialization. This sedentary lifestyle non-communicable diseases with proper implementation of along with changed food habit has lead in the emergence dietary and lifestyle practices. Ayurveda has vast scope in of many diseases, and one of them is Prameha which in this area. Ayurveda considers improper and unnatural food turn leads to Madhumeha on advancement. On the basis of habits and lifestyle as important factors in causation of its symptomatology, Madhumeha can be correlated to the disease. Undigested, junk food, and accumulated wastes are features of DM. DM is a metabolic disorder of carbohydrate, considered toxic as they produce changes in blood, lymph, fat, and protein characterized by hyperglycemia with or and other body fluids resulting in imbalance of elements.[47] without glycosuria. DM is aggressively progressive, and the With regulated diet, many diseases can be prevented and prognosis is poor unless definite measures are taken to control cured, and without that, drugs cannot give a real/lasting the disease. At the present time, there is no known cure for cure. Ideal diet according to ayurveda should be nutritionally DM and even with proper medical management; prognosis balanced, pleasing to senses, easily digested, fresh and

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S216 Dubey and Dubey: Role of Ayurveda and Yoga in Management of Prameha natural, obtained, prepared, served, and eaten with a pure 11. Sharma RK, Bhagawan D. Eng. Translation on Charaka and calm mind and taken in moderation.[48] A diet which is Samhita. Sutra Sthan Chapter 21/50-58. Varanasi: pleasantly agreeable, taken in appropriate amount at proper Chowkhambha Sanskrit Series Office; 2009. time and easily digestible, satisfies our senses and nourishes 12. Sharma RK, Bhagawan D. Eng. Translation on Charaka our body.[49] Yogic practices reduce stress, increase insulin Samhita. Sutra Sthan, Chapter 6/8-46. Varanasi: sensitivity, and also reduce fat. Chowkhambha Sanskrit Series Office; 2009. 13. Sharma RK, Bhagawan D. Eng. Translation on Charaka Samhita, Sutra Sthan,Chapter 8/17-29. Varanasi: CONCLUSION Chowkhambha Sanskrit Series Office; 2009. 14. Sharma RK, Bhagawan D. Eng. Translation on Charaka Prameha vis a vis. DM is our modern epidemic affecting Samhita. Chikitsa Sthan, Chapter 1/4/30-35. Varanasi: population. It results from unfavorable modification of Chowkhambha Sanskrit Series Office; 2009. lifestyle and dietary habits which are associated with 15. Sharma RK, Bhagawan D. Eng. Translation on Charaka urbanization.[50] Ayurveda advocates the proper use of diet Samhita. Chikitsa Sthan, Chapter 1/1/7-8. Varanasi: and regulation of lifestyle from very early life, Therefore, Chowkhambha Sanskrit Series Office; 2009. various Ayurvedic measures followed as per instructions can 16. Cui J, Yan JH, Yan LM, Pan L, Le JJ, Guo YZ, et al. prevent Prameha (DM) in primordial and primary stages and Effects of yoga in adults with Type 2 diabetes mellitus: can also stop the progress of the disease to later stages. Yogic A meta-analysis. J Diabetes Investig 2017;8:201-9. practices such as Pranayam, Paschimotanasa, Dhanurasana, 17. Shastri KN. Charaka Samhita with Commentary. 22nd ed. Bhujangasana, Halasana, Vajrasana, Ardhamatsyendrasana, Varanasi: Chaukhambha Vaidya Bhawan; 1996. p. 501-7. and so on are beneficial in DM. Various studies have shown 18. Shastri AD. Susruta Samhita with Commentary. that yogic practices decrease blood sugar (fasting and Chikitsa Sthana-11/3. Varanasi: Chaukhanbha Surbharti postprandial), reduce insulin resistance, improve insulin Prakashan; 2003. p. 59. sensitivity, decrease blood pressure, and also improve 19. Vidyadhar S. Charaka Samhita with Commentary. 1st ed., exercise tolerance.[49] Vol. 1, 2. Varanasi: Chaukhambha Surbharti Prakashana; 1998. p. 177. 20. Vidyadhar S. Charaka Samhita with Commentary. REFERENCES Sharirsthana. 8/21. 1st ed., Vol. 1, 2. Varanasi: Chaukhambha Surbharti Prakashana; 1998. 1. Shastri AD. Susruta Samhita with commentary. Varanasi: 21. Trikamji AJ, editor. Charaka Samhita (Sanskrit) by Chaukhanbha Surbharti Prakashan; 2003. p. 255. Agnivesha revised by Charaka and Dridhbala with the 2. Chandra VL. Astanga Hridaya with Commentary. Ist Ayurveda Dipika Commentary of Chakrapanidatta. 4th ed. Reprint. New Delhi: Moti Lal Banarasi Dass Publishers; Varanasi: Chaukhamba Sanskrit Sansthan; 1996. p. 344. 1990. p. 324. 22. Brahmanand T. Charaka Samhita wirh Commentary. 3. Brahmanand T. Charaka Samhita wirh Commentary, Reprint Edition. Vol. 1. Sutrasthana Chapter 17 Shloka Shloka 40 Reprint Edition, Vol. 1. Ch. 25. Varanasi: 78-9. Varanasi: Chaukhambha Surbharti Prakashan; 1991. Surbharti Prakashana; 1991. 23. Park’s PK. Text Book of Preventive and Social Medicine. 4. Chandra VL. Astanga Hridaya with Commentary. Ist 15th ed. Jabalpur, M.P: Banarsi Das Bhawan Publishers, Reprint. New Delhi: Moti Lal Banarasi Dass Publishers; Press Nagar; 2007. p. 330. 1990. p. 116. 24. Chandra VL. Astanga Hridaya with Commentary. Ist 5. Brahmanand T. Charaka Samhita wirh Commentary, Reprint New Delhi: Moti Lal Banarasi Dass Publishers; Reprint Edition. Vol. 1. Indriya Sthana Chapter 9 Shloka 1990. p. 324. 8-9. Varanasi: Chaukhambha Surbharti Prakashana; 1991. 25. Sharma RK, Bhagawan D. Eng. Translation on Charaka 6. Shastri AD. Susruta Samhita with Commentary. Varanasi: Samhita. Sutra Sthana Chapter 30/26. Varanasi: Chaukhanbha Surbharti Prakashan; 2003. p. 126. Chowkhambha Sanskrit Series Office; 2009. 7. Chandra VL. Astanga Hridaya with Commentary. Ist 26. Sharma RK, Bhagawan D. Eng. Translation on Charaka Reprint. New Delhi: Moti Lal Banarasi Dass Publishers; Samhita. Vimana Sthana, Chapter 8/94. Varanasi: 1990. p. 223. Chowkhambha Sanskrit Series Office; 2009. 8. Brahmanand T. Charaka Samhita wirh Commentary. 27. Sharma RK, Bhagawan D. Eng. Translation on Charaka Reprint Edition, Vol. 1. Varanasi: Chaukhambha Samhita, Sutra Sthana, Chapter 11/35. Varanasi: Surbharti Prakashana; 1991. Chowkhambha Sanskrit Series Office; 2009. 9. Park’s PK. Text Book of Preventive and Social Medicin. 28. Sharma RK, Bhagawan D. Eng. Translation on Charaka 15th ed. Jabalpur, M.P: Banarsi Das Bhawan Publishers; Samhita. Vimana Sthana, Chapter 1/21. Varanasi: 2007. p. 305. Chowkhambha Sanskrit Series Office; 2009. 10. Brahmasankara M. Hindi Commentary on Bhava 29. Datt SA. Sushruta Samhita by Maharishi Sushruta with Prakash of Shri Bhava Mishra. 4th ed., Vol. 1. Ch. 5. Ayurveda Tattva Sandipika Commentary. Uttartantra, Varanasi: Chaukhambha Sanskrit Sansthan; 1997. Chapter 64/56. 11th ed., Vol. 2. Varanasi: Chaukhambha

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Sanskrit Sansthan; 1997. Charaka Samhita. Sutra Sthana Chapter 7/33. Varanasi: 30. Datt SA. Sushruta Samhita by Maharishi Sushruta with Chowkhambha Sanskrit Series Office; 2009. Ayurveda Tattva Sandipika Commentary. Uttartantra, 41. Munjal YP. Editor-in-Chief, API Textbook of Medicine. Chapter 5. 11th ed., Vol. 2. Varanasi: Chaukhambha Part 12 Chapter 32. 10th ed. Parel, Mumbai: Published Sanskrit Sansthan; 1997. by the Association of Physicians of India, Distribution: 31. Sharma RK, Bhagawan D. Eng. Translation on Charaka National Book Depot; 2015. Samhita, Sutra Sthan,Chapter 6/8-46. Varanasi: 42. Ravi RJ. Sulabh Yogashastra. Ist ed. Varanasi: Chowkhambha Sanskrit Series Office; 2009. Chaukhambha Sanskrit Sansthan; 1992. p. 25. 32. Sharma RK, Bhagawan D. Eng. Translation on 43. Datt SA. Sushruta Samhita by Maharishi Sushruta Charaka Samhita Sthan, Chapter 8/17-29. Varanasi: with Ayurveda Tattva Sandipika Commentary. Chowkhambha Sanskrit Series Office; 2009. Chikitsasthana, Chapter 11/11-12. 11th ed., Vol. 1. 33. Datt TR. Hindi commentary on Ashtanga sangraha of Varanasi: Chaukhambha Sanskrit Sansthan; 1997. Vriddh Vagbhatta. Sutrasthan, Chapter 4/46. 2nd ed. 44. Anantharaman TR. In: Yoga as Science. Vol. 21-23. Varanasi: Vaidya Chaukhambha Sanskrit Pratisthan; 1992. Varanasi: Prajna; 1977. p. 477. 34. Brahmanand T. Charaka Samhita wirh Commentary. 45. Tirtha SS, Pradeep PY. Vikram Samvat. Reprint 32nd ed. Reprint Edition, Vol. 1. Charak Chikitsa Chapter 6 Gorkhpur: Geeta Press; 2068. Shloka 15-16. Varanasi: Chaukhambha Surbharti 46. Sahay BK. Role of Yogic Practices in the Prevention of Prakashana; 1991. NIDDM in Abstracts of the 15th International Diabetes 35. Teary PV. English Translation and Commentary on Federation Congress at Kobe; 1994. p. 95. Kashyap Samhita. Khilsthana, Chapter 4/5-6. Varanasi: 47. Sharma RK, Bhagawan D. Eng. Translation on Charaka Chaukhambha Vishwabharti; 2002. Samhita. Sutra Sthana Chapter 9/4-5. Varanasi: 36. Teary PV. English Translation and Commentary on Chowkhambha Sanskrit Series Office; 2009. Kashyap Samhita. Khilsthana, PP469. Varanasi: 48. Sharma RK, Bhagawan D. Eng. Translation on Charaka Chaukhambha Vishwabharti; 2002. Samhita. Sutra Sthana Chapter 27/349-350. Varanasi: 37. Sharma RK, Bhagawan D. Eng. Translation on Charaka Chowkhambha Sanskrit Series Office; 2009. Samhita. Vimana Sthana Chapter 2/3. Varanasi: 49. Sharma RK, Bhagawan D. Eng. Translation on Charaka Chowkhambha Sanskrit Series Office; 2009. Samhita. Nidana Sthana Chapter 6/11.Varanasi: 38. Sharma RK, Bhagawan D. Eng. Translation on Charaka Chowkhambha Sanskrit Series Office; 2009. Samhita. Vimanasthana, Chapter 1/21. Varanasi: 50. Park’s PK. Text Book of Preventive and Social Medicine. Chowkhambha Sanskrit Series Office; 2009. 15th ed. Jabalpur, M.P: Banarsi Das Bhawan Publishers, 39. Chandra VL. Astanga Hridaya with Commentary. Ist Press Nagar; 2007. p. 328. Reprint. Chikitsasthana Chapter 12/33. New Delhi: Moti Lal Banarasi Dass Publishers; 1990. 40. Sharma RK, Bhagawan D. Eng. Translation on Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S218 Teratology from spectacles of Ayurveda

Jaisawal Vaibhav Department of Kaumarbhritya/Balroga, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

In Ayurveda, the description about the congenital birth defects has been mentioned in many places. Ayurveda has also given some quotes on the anomalies or congenital defects precipitating in the fetus and stressed on factors that attached to the defective Shukra (sperm), Shonit (ovum), Atma (Soul), Kaal (time), and Aahar Vihar (habitat and dietetic regimen of the mother). Teratology is the study of abnormal development or congenital malformations, which may be caused by exposure to various chemicals, physical factors, and environmental factors. Alterations

REVIEW ARTICLE REVIEW of morphogenesis, alterations of central nervous system function, other functional impairments, death of the conceptus, embryo, or fetus, prenatal-onset growth deficiency, and carcinogenesis are teratogenic effect seen in human. These all type of descriptions by our Acharyas strongly suggests that they have got knowledge about the teratogens.

Key words: Congenital defects, environmental factors, fetus

INTRODUCTION teratogen and teratogenic changes in the fetus. That could be established with the teratological knowledge of the modern n Vedic and other contemporary literature, medical science. This information suggests the knowledge of the matter related to the abnormal growth Teratogenic factor during the ancient period was well known. Iand development in intrauterine life and congenital malformation has limited dealing In Ayurveda, the description about the congenital birth in comparison to the description present in defects has been mentioned in many places. Ayurveda has Ayurvedic literature Atharva Veda, Shatpath also given some quotes on the anomalies or congenital defects Brahmana, YajnavalkyaSmrti, Matsya Purana, precipitating in the fetus and stressed on factors that attached and Garbhopanihada in which there is wide to the defective Shukra (sperm), Shonit (ovum), Atma (Soul), description of congenital anomalies and birth Kaal (time), and Aahar Vihar (habitat and dietetic regimen of defect were present. the mother).

Atharva Veda has described about the invisible Charaka Samhita has also mentioned about the birth defects. factors available in the labor room, very close to In the Sharira Sthana, about the defects in impairment of woman (Pregnant) and which are likely to kill the shape, color, sensory, and motor organs of the offspring. the fetus when it is partially delivered. A type of Description of the Dviretas, Pavanendriyatva, samskaravahi medicine has been advocated to kill or remove suggests that at that time congenital birth defects were also [16] them (A.V. 18/6/19). present. According to Charak samhita, the pregnant lady should avoid the use of drugs of high potency, Vyavaya According to Garbhopanihada described about (sexual intercourse), and Vyayama (physical exercise) for the Psychological state of women. Mental pregnant lady (Ch.Sh.25/40). stress during pregnancy leads to congenital abnormalities such as blindness and deformed In the Sushruta Samhita mentioned about some works, act body organs such as vertebral column and causes, which can cause congenital defect in the fetus. The dwarfism in newborn baby. That type of description has a direct concern with true mental Address for correspondence: stress (Garbhopanihada/3).[16] Jaisawal Vaibhav, Department of Kaumarbhritya/ Balroga, Faculty of Ayurveda, Institute of Medical The description of Vedic literature about the Sciences, Banaras Hindu University, Varanasi, infection, maternal causes, mental stress, Uttar Pradesh, India. Phone: +91-8004232639. and other genetic and environmental factors E-mail: [email protected] establishing the relationship in between the

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S219 Vaibhav: Teratology from spectacles of Ayurveda pregnant woman should avoid copulation, physical exercise, death of fetus, growth retardation, visible malformation, too much of excessive diet or attenuation (making the body and functional disorder along with specific effects such as very plumpy or very emaciated, respectively), sleeping carcinogenesis and recognizable syndromes, magnitude of during day and keeping awake at night; grief, riding on risk (absolute, relative), and prenatal diagnosis (invasive and animals/vehicles, fear, sitting on her heels for long periods, non-invasive techniques).[3] indulging in oleation and other therapies, bloodletting at unsuitable time, and suppression of the urges of the body (of Any drug or chemical given to the mother will cross the urine, faces, flaws, etc.). (Su.Sh.3/16). All the above factors placenta to some extent unless it is destroyed or altered during vitiate the doshas of the pregnant lady, in turn, the affected placental passage or its molecular size or lipid solubility doshas can cause injury or trauma to the same parts of the limits transplacental transfer. The onset of this placental fetus as the same type injury mother has got (Su.Sh.3/17).[12] transfer starts at the fifth embryonic week to 7th gestational week. For drugs or chemicals with low molecular weight, A pregnant lady should avoid Garbhopghatakarabhavas (the the transplacental passage to the fetus is based on the factors which can destroy the fetus) for avoiding any injury concentration gradient.[7,17] to the fetus such as all the types of heavy, excessive hot, bitter taste food, and violent exercise. She should not wear There is no specific constellation of fetal/neonatal signs and red clothes to prevalent the (attacks of) gods, demons, and symptoms that are pathognomonic of infection. Each infectious their followers. She should not take intoxicating wines, ride agent, depending on the time of exposure and viral-host over vehicles, and eat meat, should abstain completely from interactions, can result in a diverse range of manifestations.[3] the things which are unfavorable to all the sense organs and many others which (elderly) woman know (Ch.Sh.4/18).[13,14] TERATOGENIC EXPOSURES In Astanga sangraha, Vagabhatta has also described about the birth defects. According to him Doshas get vitiated and There are many factors, which are responsible for the causes defect in the fetus. When Vãta, develops upward teratogenic changes. They are teratogenic agents, drugs movement (which is abnormal) and dries up the channels of dosage to embryo or fetus and period of pregnancy.[1,2,7] rasa in the fetus, the future child will be either a patient of vãtaroga or one born with deficient/poorly developed parts; or it (the fetus) may even remain inside the abdomen for Agent many years (A.Sa.Sh.2/20). If the pregnant women indulges Teratogenicity also depends on the nature of the chemical, constantly in foods and activities which cause increase of physical or infectious agent, inherent developmental toxicity, Vãta, then Vãta getting increased abnormally, travels all over and the capacity to produce other kinds of toxicity in the her body and also in the uterus, and produces many diseases mother. of Vãta origin in the child; the child may become inactive, deaf, mute, of nasal speech, stammering, lame, hunch-back, dwarf, of deficient organs (in number) or of extra organs, or Dosage to Embryo or Fetus any other Väta diseases (A.Sa.Sh.2/34).[8-11] Teratogenicity may occur due to single, repeated, or Maharishi Kashyap has indicated the adverse effect of the chronic exposure, duration of exposure. Another factor also smoking of the mother during her prenatal period. In his influences the teratogenicity such as maternal dose, maternal opinion, such activities are likely to produce congenital route of exposure, maternal absorption, maternal metabolism abnormalities blindness, sickness, discoloration of the and clearance as well as, and placental transfer. newborn baby, and even Garbhapata or abortion (Kashyap/ chi. 10/20).[15] Period of Pregnancy These all type of descriptions by our Acharyas strongly Exposure of specific teratogen during first, second, or third suggests that they have got knowledge about the teratogens trimester may lead to the development of congenital anomalies. and what is the outcome of that. Hence, they have also told In other words, specific congenital anomalies may be the about the precautions should be taken by pregnant women result of teratogenicity drug exposure between conception to avoid these untoward effects. In modern science, they and onset of embryogenesis, during organogenesis, and fetal also described agents such as physical, chemicals, and period. environmental that can cause teratological effects.

Characterization of teratogenic exposures involves the Other Factors specific agent, the dose of the agent, the gestational age, and other factors such as genetic susceptibility.[3] Characterization Other factors are genetic susceptibility of mother, genetic of teratogenic effects includes general effects such as susceptibility of the fetus, other concurrent exposures,

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S220 Vaibhav: Teratology from spectacles of Ayurveda maternal illness, or other condition associated with exposure, 1941;3:35-46. availability of tests to quantify the magnitude of maternal 6. Lenz W. Malformations caused by drugs in pregnancy. exposure.[4] Am J Dis Child 1966;112:99-106. 7. Wilson JG. Current status of teratology. General principles and mechanisms derived from animal studies. TERATOGENIC EFFECT In: Handbook of Teratology. New York, NY: Plenum Press; 1977. p. 1-47. Alterations of morphogenesis, Alterations of CNS function, 8. Chaukhamba Sanskrit Sansthan. Astang Hrdayam of other functional impairments, Death of the conceptus, embryo, Vagbhata, Edited with ‘Vidyotini’ Hindi Commentary by or fetus, Prenatal-onset growth deficiency, Carcinogenesis. KavirajaAtrideva Gupta-Edited by Vaidya Yadunandana Specific effect includesrecognizable syndromeandOther Upadhyaya. Varanasi: Chaukhamba Sanskrit Sansthan; distinctive features.[5,6] 1994. p. 221001. 9. Krishnadas Academy. Astanga Hridayam English translation, by Prof. K.R. Srikantha Murthy. Vol. 02. CONCLUSIONS Varanasi: Krishnadas Academy; 2000. 10. Chaukhambha Orientalia. Astanga Samgraha, English These all type of descriptions by our Acharyas strongly translation by Prof. K.R. Srikantha Murthy. Vol. 02. suggests that they have got knowledge about the teratogens Varanasi: Chaukhambha Orientalia; 1999. and what is the outcome of that. Hence, they have also told 11. Krishnadas Academy. Astanga Samgraha, Hindi about the precautions should be taken by pregnant women commentary, Vol-1 and Vol-2 by Atrideva Gupta. to avoid these untoward effects before taking allopathic Varanasi: Krishnadas Academy; 2002. medicine or even ayurvedic medicine if it is not formed 12. Sushruta M. Sushruta Samhita, Sri DalhanaAcharya, Sri purely following all standard parameter. GayadasAcharya, Vaidya Yadavaji Trikamji Acharya. Varanasi: Chaukhambha Sanskrit Sansthan; 2005. 13. Chaukhambha Sanskrit Sansthan. Agnivesha, Charaka Samhita, Vaidya Yadavaji Trikamji Acharya. Varanasi: REFERENCES Chaukhambha Sanskrit Sansthan; 2004. 14. Chaukhamba Sanskrit Series Office. Carakasamhita 1. Agency for Toxic Substances and Disease Registry with English translation by Dr. Ram Karan Sharma (ATSDR). Toxicological Profile for Mercury. Atlanta, and VaidyaBhagvan Dash Vol. 4. Varanasi (India): GA: U.S. Department of Health and Human Services, Chaukhamba Sanskrit Series Office; 1997. Public Health Service; 1999. 15. Chaukhambha Sanskrit Sansthan. Kasyapa Samhita with 2. Briggs GG, Freeman RK, Yaffe SJ. Drugs in Pregnancy ‘Vidyotini’ Hindi commentary and Hindi translation by and Lactation. 7th ed. Philadelphia: Lippincott Williams Sri Satyapala Bhisagacharya. 3rd ed. Varanasi (India): and Wilkins; 2005. Chaukhambha Sanskrit Sansthan. 3. Friedman JM, Hanson JW. Clinical Teratology. In: 16. Motilal Banarsidas. Sanskrit-English Dictionary by Rimoin DL, Connor JM, Pyeritz RE, Korf BR, editors. Vaman Shivram Apte. New Delhi: Motilal Banarsidas, Emery and Rimoin’s Principles and Practice of Medical Head Office Bungalow Road. Genetics. 4th ed. New York: Churchville Livingston; 17. Concept Publishing Company. Alchemy and Metallic 2002. p. 1011-45. Medicines in Ayurveda by Vaidya Bhagwan Dash. 4. Archibald EG. The incidence of alkaptonuria: A Study in New Delhi: Concept Publishing Company; 1986. chemical individuality. Lancet 1902;2:1616-20. 5. Gregg, NM. Congenital cataract following German measles in the mother. Trans Ophthalmol Soc Aust Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S221 A review on management of diabetes mellitus (prameha): Current scenario

Vandana Singh1, Arpit Shrivas2, Bhuwal Ram1 1Department of Dravyaguna, Faculty of Ayurveda, IMS, BHU, Varanasi, Uttar Pradesh, India, 2Department of Kayachikitsa, Faculty of Ayurveda, IMS, BHU, Varanasi, Uttar Pradesh, India

Abstract

The traditional medicine is increasingly entreating through the practitioners in the treatment of many diseases. Among the medicament used, plant drugs constitute an important part as they play a key role for the development of new drugs. However, due to increase in lifestyle modifications leading to different lifestyle diseases, treatment

REVIEW ARTICLE REVIEW methodology focuses more the management principles as the first-line approach along with the herbal drugs. Diabetes mellitus (DM) refers to a group of common metabolic disorders characterized by hyperglycemia with disturbance of carbohydrate, fat, and protein metabolism resulting from defects of insulin secretion, insulin action, or both. Several distinct types of DM are caused by a complex interaction of genetics and environmental factors. Etiology of the DM that is factors contributing to hyperglycemia which include reduced insulin secretion, decreased glucose utilization, and increased glucose production. Diabetes is known as Prameha, which has been discussed in Ayurveda since antiquity.

Keywords: Diabetes mellitus, herbal drugs, lifestyle, Prameha

INTRODUCTION PATHOGENESIS[8,9]

Due to causative factors (wrongful diet - high glycemic food, lack of ccording to the World Health exercise, etc.) Organization, diabetes is among the Doshas get imbalanced top 5 leading cause of death in the (specifically kledakkapha, pachak pitta, samanvayu) – (high blood A sugar, insulin secreted by pancreas) world. Diabetes is the world’s fastest growing chronic diseases. Currently, 246 million Agnimandya (dhatvagnimadhya) – (cell become to resistant to people are affected worldwide. The number insulin)

expected to rise to 380 million by 2025.

Each year 3.8 million death are attributable Culminates all dushyas (specifically medodhatu) – (more glucose to diabetes. Every 10 s a person dies from present in the blood) diabetes. Ancient text describes 20 types of Prameha,[1] out of these 10 are due to kapha Kledavriddhi (unnecessary excessive body fluid oozed out from all dhatu) – [2] (early stage), 6 are due to pitta (acute (body tries to dilute high blood glucose) [3] [4] stage), and 4 are due to vata (chronic stage). diabetes mellitus (DM) (Prameha) explicit two main etiological factors, i.e., Sahaja Body tries to excrete in the form of urine (polyuria) (hereditary/congenital) due to unnatural and abnormal shukra and shonita and the other one Apathyanimittaj due to improper dietary intake and activities.[5] Causative factors of Prameha include sedentary lifestyle, sleeping during daytime, intake of all other kapha promoting substance, laziness, consuming Address for correspondence: food which are cold, unctuous, fatty, and Vandana Singh, Department of Dravyaguna, Faculty of Ayurveda, IMS, BHU, Varanasi - 221 005, Uttar Pradesh, sweet food[6] and food, drinks, and activities India. Phone: +91-8756271981. E-mail: vandy.bhu@ which aggravates meda, mutra, and kapha are gmail.com main characteristics for genesis of Prameha.[7]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S222 Singh, et al.: Diabetes management current scenario

Classification Value for Fasting Blood Glucose pharmacologic intervention is required, metformin is the Levels are[10] only drug that is recommended in conjunction with diet and exercise in high-risk patients (those with both impaired • Normal blood glucose: 4–6 mmoL/L glucose tolerance [IGT] and impaired fasting glucose).[15] • Moderate blood glucose: 4–7 mmoL/L Triangular approach toward prevention of the disease exhibits: • High blood glucose: Above 7 mmoL/L. 1. Ahara (diet) However, the symptoms of diabetes may not appear until 2. Vihara (lifestyle) blood glucose level is higher. Hence, some people may have 3. Aushadhi (medicine). diabetes without knowing about it. Classical symptoms of Prameha comprises excessive thirsty, passing more urine, Diet plan of an individual is based on height, weight, age, feeling tired and lethargic, always feeling hungry, having sex, physical activity, and nature of the disease conditions in cuts, that is, heals slowly, itching, skin infections, blurred managing diabetes. Modified lifestyle and faulty Agni are the vision, gradually putting weight, mood swings, feeling dizzy, potential source of this disease, so more emphasis should be and leg cramps.[11] given on diet and biopurificatory measures. That is described as “Nidana Parivarjana” in the classics. Hence, ahara which do not increase body weight and opposite to etiological factors of PREVENTION: CURRENT SCENARIO[12] Prameha is advised to the patient.[16] Sushruta also elucidates that in advance stages of Prameha, regular physical exercise • Maintaining a healthy weight should be practiced, wrestling, active sports, horse riding, • Regular physical activity or an elephant, long walks, pedestrian journeys, practicing • Making healthy food of choices archery, casting of javelins, etc., should be done.[17] Ayurveda • Managing blood pressure <140/80 mmHg* recommends drugs having Tikta (bitter), Katu (pungent), • Managing cholesterol levels*. and Kasaya (astringent) Rasa[18] in Prameha as it is kapha 1. LDL: <100 mg/dL predominant disease, and dushyantha has the same nature 2. Triglycerides: <150 mg/dL as that of kapha.[19] Susruta clearly indicated the decoction 3. HDL: >40 mg/dL (men), >50 mg/dL (women). of Salasaradi Gana drugs with Shilajatu for the treatment of • No smoking Prameha.[20] Popular and effective herbs used in the treatment • No alcohols of the disease are Amalki (Indian Gooseberry), Karela (bitter • Screening of prediabetes with an informal assessment Melon), Methi (Fenugreek), Jamun seed, Gurmar, Vijaysar, of risk factors should be considered in asymptomatic Haridra (turmeric), Neem, Triphala, Guduchi, Daruharidra, adults. Prediabetes criteria include[13] Bel, Chairayata, Kutki, Devadaru, Shilajatu, etc., are included in Samana Chikitsa also Panchkarma procedures such as 1. Fasting blood glucose: 100–125 mg/dL (5.6–6.9 vaman, virechan, and basti are mentioned under Shodhan mmoL/L: IFG) chikitsa.[21] Individuals who lose 7% of their body weight and 2. 2 h plasma glucose: 140–199 mg/dL (7.8–11.0 maintain 150 min of exercise weekly can reduce the rate of mmoL/L: IGT) progression from IGT to diabetes by 58%.[22] 3. HbA1C: 5.7–6.4%. • Regular monitoring blood glucose level* 1. Fasting blood glucose: ≥7.0 mmoL/L DISCUSSION 2. 2-h plasma glucose: ≥11.1 mmoL/L 3. HbA1C: <7%. On expositing all the management principles, dietary • Avoiding sweet, salty, and acidic taste of food which requirements for a diabetic person should involve eating are Kapha producing and increase the risk of diabetes. habits which include wheat, rye, barley and, for some, oats. Pungent, bitter, and astringent taste of food are less Kapha Furthermore, avoid eating or drinking anything containing a lot producing food and reduce/prevent the risk of diabetes.[14] of sugar such as cakes, sweets, and chocolate. Vegetables that • Delay or prevent complications of diabetes. can be consumed in larger quantities such as cabbage, mint, spinach, bitter gourd, lady’s finger, cauliflower, cucumber, *HbA1C, blood pressure, and cholesterol goals need to be carrots, radish, onion, gourd, and pumpkin. It is very important altered for the individual based on age, duration of diabetes, to never skip any meal and always eat small amount of meal health history, and other present health conditions. frequently. Person should never overeat at any time of the day. Intake of large quantities of rice, potatoes, and bananas must be avoided as these can raise the blood sugar level. Reducing the MANAGEMENT PRINCIPLES intake of salt in the food lowers the risk toward CVS problems. Regular walk and exercise should be the chief component of The American Diabetes Association endorses lifestyle daily lifestyle procedures. Drinking plenty of water (approx modifications as the initial treatment for diabetes. If 2.2-3 litres a day). The person should try to choose low or

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S223 Singh, et al.: Diabetes management current scenario non-fatty dairy products in their meals. These practices will prevention measures and improvement in daily lifestyle habits ultimately minimize the dependency over medicines and are taken into prime consideration for maintaining proper health. insulin and improve the healthy lifestyle. Therefore, every Through triangular approach of Ahara (diet), Vihara (exercise), treatment advice should include dietary and exercise plan to a and Aushadhi (medicine), it can be well managed by Ayurveda. person along with the therapeutic advice. Furthermore, further, These attributes of Ayurveda play a major role in disease exploration of the same should be considered for the proper prevention and promotion of health with a better quality of life. social and economic development of the individual and the Ayurveda with its strong scientific fundamentals with unique society in the management of lifestyle disorders. features will be emerging as the best medical system. Thus, the system requires scientific validation for global acceptance. Thus, nutritional recommendation for a diabetic individual can be grouped into following key points: REFERENCES i. Person should be emphasized toward healthy food choices and portion of food control which is more 1. Agnivesha. Charak Samhita, Vidyotini Hindi helpful for those with type 2 diabetes who are not taking Commentary, Shastri Kashinatha and Chaturvedi insulin or prone to hypoglycemia. Gorakhanatha, Nidanasthana, Pramehanidanaadhyaya ii. Adequate weight loss achieved by the combination of (4;3), Varanasi: Chaukhambha Bharti Academy; 2011. lifestyle modification and the lowering calorie intake p. 630. directly benefits overweight or obese adults with type 2 2. Agnivesha. Charak Samhita, Vidyotini Hindi diabetes and also those with prediabetes. Commentary, Shastri Kashinatha and Chaturvedi iii. Emphasis on intake of food higher in fiber and lower Gorakhanatha, Nidanasthana, Pramehanidanaadhyaya in glycemic load and carbohydrate intake from whole (4; 10). Varanasi: Chaukhambha Bharti Academy; 2011. grains, vegetables, fruits, legumes, and dairy products, p. 634. should be advised over other sources, especially those 3. Agnivesha. Charak Samhita, Vidyotini Hindi containing sugars. Commentary, Shastri Kashinatha and Chaturvedi iv. Sugar-sweetened beverages with minimal consumption Gorakhanatha, Nidanasthana, Pramehanidanaadhyaya of foods with added sugar should be avoided to control (4; 24). Varanasi: Chaukhambha Bharti Academy; 2011. weight and reduce risk for CVD and fatty liver that displace p. 636. healthier and more nutrient-dense food in our daily diet. 4. Agnivesha. Charak Samhita, Vidyotini Hindi v. Intake of protein tends to increase insulin response Commentary, Shastri Kashinatha and Chaturvedi without increasing plasma glucose concentrations. Gorakhanatha, Nidanasthana, Pramehanidanaadhyaya Therefore, carbohydrate sources high in protein should (4; 39). Varanasi: Chaukhambha Bharti Academy; 2011. not be advised to treat or prevent hypoglycemia. p. 638. vi. An eating plan emphasizing elements of a diet rich in 5. Susruta. Susruta Samhita, Ayurveda-Tattva- monounsaturated fats is an effective alternative to a low- Sandipika, Dr. Ambikadutt, Chikitsasthana, Prameha fat, high-carb diet which improves glucose metabolism Chikitsaadhyaya (11; 3). Varanasi: Chaukhambha and lowers CVD risk. Sanskrita Sansthana; 2013. p. 75. vii. People with diabetes along with alcohol consumption 6. Agnivesha. Charak Samhita, Vidyotini Hindi are at an increased risk for hypoglycemia, especially if Commentary, Shastri Kashinatha and Chaturvedi taking insulin or insulin secretagogues. Gorakhanatha, Chikitsasthana, Pramehanidanaadhyaya viii. The use of non-nutritive sweeteners possibly reduces (6; 4). Varanasi: Chaukhambha Bharti Academy; 2011. overall calorie and carbohydrate intake if substituted for p. 227. caloric sweeteners. 7. Agnivesha, CharakSamhita, Vidyotini Hindi ix. Children with diabetes/prediabetes: At least 60 min/day Commentary, Shastri Kashinatha and Chaturvedi physical activity should be recommended. Most adults Gorakhanatha, Nidanasthana, Pramehanidanaadhyaya with types 1 and 2 diabetes are endorsed for 150+ min/ (4; 5). Varanasi: Chaukhambha Bharti Academy; 2011. week of moderate-to-vigorous activity over at least p. 632. 3 days/week with no more than 2 consecutive days 8. Agnivesha. Charak Samhita, Vidyotini Hindi without exercise. Shorter durations (minimum 75 min/ Commentary, Shastri Kashinatha and Chaturvedi week) of vigorous-intensity or interval training are Gorakhanatha, Chikitsasthana, Pramehanidanaadhyaya sufficient for younger and physically fit individuals. (6; 5 Varanasi: Chaukhambha Bharti Academy; 2011. p. 228. 9. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, CONCLUSION Loscalzo J, editors. Harrison’s Principles of Internal Medicine. 15th ed., Vol. 02, 333-Diabetes Mellitus. Ayurveda offers a balanced and holistic approach in treating New York: McGraw- Hill; 2003. p. 2114. DM. Prevention is better than cure, on this node, nowadays, 10. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J,

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S224 Singh, et al.: Diabetes management current scenario

Loscalzo J, editors. Harrison’s Principles of Internal Ayurveda (1941-2000). 3/7. New Delhi: Chaukhamba Medicine. 15th ed., Vol. 02, 333-Diabetes Mellitus. Sanskrit Pratishthana; 2005. p. 431. New York: McGraw- Hill; 2003. p. 2111. 18. Agnivesha. Charak Samhita, Vidyotini Hindi Commentary, 11. Agnivesha, CharakSamhita, Vidyotini Hindi Commentary, Shastri Kashinatha and Chaturvedi Gorakhanatha, ShastriKashinatha and ChaturvediGorakhanatha, Sutrasthana, Dirghamjivitiyaadhyaya (1; 66). Varanasi: Chikitsasthana, Pramehanidanaadhyaya (6; 13). Chaukhambha Bharti Academy; 2011. p. 39. Varanasi: Chaukhambha Bharti Academy; 2011. p. 234. 19. Agnivesha, Charak Samhita, Vidyotini Hindi 12. Evert AB, Boucher JL, Cypress M, Dunbar SA, Commentary, Shastri Kashinatha and Chaturvedi Franz MJ, Mayer-Davis EJ, et al. Nutrition therapy Gorakhanatha, Nidanasthana, Pramehanidanaadhyaya recommendations for the management of adults with (4; 11). Varanasi: Chaukhambha Bharti Academy; diabetes: Position statement by the ADA. Diabetes Care 2011. p. 634. 2013;37:363821-42. 20. Susruta. Susruta Samhita, Ayurveda-Tattva-Sandipika, 13. American Diabetes Association Standards of Medical Dr. Ambikadutt, Chikitsasthana, Madhumeha Care in Diabetes. Classification and diagnosis of Chikitsaadhyaya (13; 11). Varanasi: Chaukhambha diabetes. Diabetes Care 2017;40 Suppl. 1:S11-24. Bharti Academy; 2013. p. 82. 14. Sharma PV. Deo S, Anugrah S, editor. Six Decades of 21. Agnivesha. Charak Samhita, Vidyotini Hindi Ayurveda (1941-2000). 3/7. New Delhi: Chaukhamba Commentary, Shastri Kashinatha and Chaturvedi Sanskrit Pratishthana; 2005. p. 432. Gorakhanatha, Nidanasthana, Pramehanidanaadhyaya 15. American Diabetes Association. Standards of (4; 49). Varanasi: Chaukhambha Bharti Academy; medical care in diabetes-2008. Diabetes Care 2011. p. 640. 2008;31 Suppl 1:S12-54. 22. Nguyen Q, Nguyen L, Felicetta J. Evaluation and 16. Susruta. Susruta Samhita, Ayurveda-Tattva-Sandipika, management of Diabetes Mellitus. Am Health Drug Dr. Ambikadutt, Uttaratantra, Aupadravikaadhyaya Benefits 2008;1:39-48. (1; 25). Varanasi: Chaukhambha Sanskrita Sansthana; 2013. p. 14. 17. Sharma PV. Deo S, Anugrah S, editor. Six Decades of Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S225 Yoga: A potential tool for curbing neurological disorders

Varnika Singh1, Vd Shalini Rai2, Vijay Kumar Rai3 1Department of Roga Nidanevum Vikriti Vigyan, All India Institute of Ayurveda, Sarita Vihar, New Delhi – 110 076, Delhi, India, 2Department of Roga Nidanevum Vikriti Vigyan, All India Institute of Ayurveda, Sarita Vihar, New Delhi, 110076, Delhi, India, 3Department of Swasthavritta and Yoga, Government Post - Graduate Ayurveda College and Hospital, Sampurnanad Sanskrit University, Varanasi – 221 002, Uttar Pradesh, India

Abstract

With the improvement of health-care services in preventive and promotive domains, developing countries

REVIEW ARTICLE REVIEW including India are passing through a phase of epidemiological transition with increasing burden of non- communicable diseases, of which a major portion is shared by neurological disorders. According to the WHO estimates, neurological disorders are responsible for between 4.5 and 11% of all illnesses ranging from low- to high-income countries which are far higher than the number of respiratory ailments, gastrointestinal disorders, or cancers, and the burden is still expected to increase. The number of disability-adjusted life years (DALYs) lost due to neurological diseases is expected to rise from 95 million worldwide in 2015–103 million in 2030. Neurologic disorders and cerebrovascular disease combined represent 7.1% of the total global burden of disease measured in DALY for all causes and ages. Further, treatment options for neurological disorders are also extremely limited with interventions including preventative measures, lifestyle changes, physiotherapy or other therapy, neurorehabilitation, pain management, medication, or operations performed by neurosurgeons. Still, the outcome is not very sure, and in many cases, the quality of life of the patients remains poor despite these ongoing therapies and conventional medicines. In this scenario, it is crucial to integrate Yoga to facilitate the needs of health-care delivery system for the management of neurological disorders. The integration of Yoga for the management of neurological disorders can help overcome the disability, improve the quality of life in the patients and will help in reducing the burden of suffering and disability due to neurological disorders. This paper will detail about the role of yoga in the management of neurological disorders and its future prospects in the prevention.

Key words: Yoga, Neurological disorders, Prevention, Management

BACKGROUND One of the major contributors to the burden of NCDs is neurological disorders. According to the WHO estimates, ith the improvement of health-care neurological disorders are responsible for between 4.5 services in preventive and promotive and 11% of all illnesses ranging from low- to high-income Wdomains, developing countries countries which are far higher than the number of respiratory including India are passing through a phase of ailments, gastrointestinal disorders, or cancers, and the epidemiological transition with increasing burden burden is still expected to increase. The number of disability- of non-communicable diseases (NCDs). Unlike, adjusted life years (DALYs) lost due to neurological diseases NCDs are chronic in nature associated with high is expected to rise from 95 million worldwide in 2015 to cost of treatment and investigation which generally 103 million in 2030. They represent a high social burden. lasts lifelong. The out-of-pocket expenditure for the NCDs is quite large and sometimes is Numerous chronic diseases related to neurological system the cause behind the non-initiation or restriction that cause severe disability among individuals are considered of treatment. The out-of-pocket expenditure is as neurological diseases.[2] Some of them are stroke, multiple also the reason for the deteriorating economic status of the families of people suffering from Address for correspondence: NCDs. The five major NCDs (cardiovascular Vd Shalini Rai, Department of Roga Nidanevum Vikriti diseases; endocrine and metabolic diseases; Vigyan, All India Institute of Ayurveda, Sarita Vihar, neoplasm; respiratory infections; and mental and New Delhi – 110 076, Delhi, India. neurological disorders) account for almost 39% E-mail: [email protected] of total health expenditures in 2004.[1]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S226 Singh, et al.: Yoga to curb Neurological disorders sclerosis (MS), epilepsy, Alzheimer disease (AD) and other of AD, PD, epilepsy, MS, migraine, tension-type headache, dementias, Parkinson disease (PD), migraine, and other peripheral neuropathies, and other neurologic disorders. neurologic disorders. Today, the purpose of health care for In the present scenario, hundreds of millions of people individuals with chronic neurological diseases is to increase the worldwide are affected by neurological disorders. capacities of patients and their families to cope with problems, Developing countries including India are passing through a improve self-care, preserve and improve skills, meet information phase of epidemiological transition with increasing load of needs, and increase independence and quality of life.[3] this disease. A significant burden is imposed on the society Interventions for neurological disorders include preventative due to the burden of neurological disorders globally. Stroke measures, lifestyle changes, physiotherapy or other therapy, is one of the leading causes of mortality and morbidity neurorehabilitation, pain management, medication, or operations worldwide.[7] Approximately 6.2 million people worldwide performed by neurosurgeons. To improve lifestyle changes and die because of stroke each year; over 80% of deaths take for preventive measures, Yoga is the best therapy which is a place in low- and middle-income countries. Neurologic science as well as an art of healthy living. Yoga is a mind-body disorders and cerebrovascular disease combined represent exercise effective for reducing stress, anxiety and depression, 7.1% of the total global burden of disease measured in DALY and improving brain function and mental health. In this paper, for all causes and ages.[8] an attempt has been made to elaborate the effect of Yoga therapy in the prevention and cure of neurological disorders. Apart from this, the availability and access to neurological care through diagnostics and therapy are very haphazardly distributed globally. Inhabitants in high-income regions have RISK FACTORS FOR NCDS an average of 402 neurologists available for every 100,000 while the figure is only 4.5 in low-income countries which Several risk factors have been associated to the development are far below acceptable levels.[8] of NCDs. They are categorized as follows:

Modifiable behavioral risk factors YOGA IN NEUROLOGICAL DISORDERS

Tobacco use, physical inactivity, unhealthy diet, and the Today’s lifestyle has brought in many challenges to health harmful use of alcohol increase the risk of NCDs. These include and has become a major cause for many ailments such as excessive smoking, physical inactivity, alcohol, and salt intake. stress, obesity among people across the world. In this context, Scientific data reveal that around 6 million deaths every year people have started looking back to the nature and that is occur due to the usage of tobacco (including from the effects of precisely where the role of alternative medicine and therapies exposure to second-hand smoke) and are projected to increase come into play. One of the therapies which is totally based to 8 million by 2030. About 3.2 million deaths annually can be on the principle of restoring natural balance and accompany attributed to insufficient physical activity.[4] More than half of human life back in harmony of body, mind, and spirit is the 3.3 million annual deaths from harmful drinking are from Yoga. Yoga is not merely a form of physical activity for the NCDs.[5] 1.7 million annual deaths from cardiovascular causes body, but it is an ancient wisdom for a happier, healthier, and have been attributed to excess salt/sodium intake.[6] calmer way of living, which ultimately leads to union with the self. The holistic approach of Yoga is well established, and it brings harmony in all stages of life and thus, known Metabolic/physiological risk factors for, health promotion disease prevention and management of many lifestyle-related disorders or NCDs.[9] Yoga is very These behaviors lead to four key metabolic/physiological changes helpful to cure neurological disorders by various means as that increase the risk of NCDs which are raised blood pressure, mentioned below. overweight/obesity, hyperglycemia (high blood glucose levels), and hyperlipidemia (elevated levels of fat in the blood). In terms of attributable deaths, the leading metabolic risk factor globally Asanas is elevated blood pressure followed by overweight and obesity and raised blood glucose. Low- and middle-income countries Postures and the asanas are the aerobic component and may are witnessing the fastest rise in overweight young children. stimulate the central nervous system release of endorphins, monoamines, and brain-derived neurotrophic factor in the hippocampus. NEUROLOGICAL DISORDERS: A HIGH SOCIETAL BURDEN Pranayam and dhyan

Neurological disorders result due to structural, biochemical, These practices have been found to regulate the emotional or electrical abnormalities in the brain, spinal cord, nerves, responses by reducing the sympathetic tone, increasing the or neurological junctions. It includes stroke, subcategories parasympathetic tone, improving the cognitive functioning

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S227 Singh, et al.: Yoga to curb Neurological disorders increasing the EEG synchrony and coherence, and causing patients more responsive to specific stimuli. Sahaja Yoga an increase in melatonin levels (promotes sleep, stimulates meditation appears to bring about changes in some of the immune system, and reduces blood pressure) and a decrease electrophysiological responses studied in epileptic patients.[12] in cortisol (less negative effects and depression) levels. Yoga in migraine Mental calmness and stress reduction Study of Yoga intervention and control groups on endothelial Yoga achieves voluntary control over autonomous nervous function in 42 patients with migraine by Naji-Esfahani et al. system by establishing equilibrium between sympathetic for 3 months reveals a statistically significant decrease in and parasympathetic through hypothalamic limbic system. plasma level of vascular cell adhesion molecule in Yoga group It reduces stress impulses, stimulates sympathetic system, compared with the control group (15.29 ± 2.1 ng/ml vs. 21.70 and eventually quietens mind. It also clears all negative ± 3.0 ng/ml, P < 0.05), whereas there was no statistically feelings and thoughts from mind leading to the reduction of significant difference in intercellular adhesion molecule depression. level between groups (19.1 ± 1.8 ng/ml vs. 20.97 ± 1.9 ng/ml P > 0.05). They found that Yoga exercises, as a Concentration and memory complementary treatment beside pharmacological treatment, can be potentially an effective way of improving vascular [13] Yoga increases concentration and improves circulation, functions in migraineurs. especially to brain leading to improved memory. Yoga in depression

RESEARCHERS AND STUDIES PROVING A meta-analysis including 12 randomized controlled trials ROLE OF YOGA IN NEUROLOGICAL (RCTs) and 619 patients by Cramer et al. on the topic of DISORDERS Yoga for depression unmasks that despite methodological drawbacks of the included studies, Yoga could be Yoga in epilepsy considered an ancillary treatment option for patients with depressive disorders and individuals with elevated levels of [14] A pilot study conducted by Rajesh et al. on 20 epileptic depression. Studies also suggest that Yoga interventions patients to assess the efficacy of Yoga meditation protocol improve depression severity in patients with a comorbid [15] (YMP) for the duration of 3 months period reveals a disorder such as cancer or fibromyalgia. reduction in seizure frequency in 19 patients, six of which recorded a seizure reduction of 50% or more. 16 patients Yoga in stroke continued the YMP beyond 3 months and 14 patients responded at 6 months, out of which 6 were seizure free Bell and Seyfer have described specific adaptations of Yoga for 3 months. Eight patients of these continued the YMP postures that can be utilized by people with limited mobility beyond 6 months and responded. It was reported that three due to neurological conditions such as MS and stroke.[16] A of them were seizure free for 6 months. They concluded pilot study with 12 weeks of Kundalini Yoga practice showed that Yoga has magical power in curing patients. Yoga can be improvements in aphasia as well as fine motor coordination helpful if confirmed through randomized trials involving a in post-stroke patients.[17] larger number of patients and may become a cost-effective and adverse effect-free adjunctive treatment in patients with Another study based on asana, pranayam, and wait-listed [10] drug-resistant epilepsies. control groups (10 weeks intervention) illustrates the positive physical and psychosocial impact, Yoga can instill Another study conducted by Lundgren et al. on a randomized in stroke victims such as greater sensation, feeling calmer, control trial with 18 subjects indicates that both acceptance becoming connected with mind and body, improvements and commitment therapy (ACT) and Yoga significantly in perceived physical strength, range of movement, body reduce seizure index. Participants in both the ACT and awareness, gait, balance, energy, concentration, confidence, Yoga groups improved their quality of life significantly as and stress.[18] measured by one of two quality of life instruments. The results of this study suggest that complementary treatments, such as ACT and Yoga, decrease seizure index and increase Yoga and schizophrenia quality of life.[11] A systematic review and meta-analysis of five RCTs with A study by Panjwani et al. on 32 subjects and patients a total of 337 patients on Yoga therapy for schizophrenia randomly divided into three groups reveals that the reduced reported moderate evidence for short-term effects on quality level of stress following meditation practice may make of life.[19]

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Yoga and post-traumatic stress disorder (PTSD) REFERENCES

Yoga breath intervention was observed to be more beneficial 1. Thakur J, Prinja S, Garg CC, Mendis S, Menabde N. compared to wait-listed controls in reducing post-traumatic Social and economic implications of noncommunicable symptoms.[20] Another RCT reported decrease in sadness diseases in India. Indian J Community Med but no change in heart rate variability by Yoga therapy in 2011;36 Suppl 1:S13-22. comparison to wait-list control group of PTSD.[21] 2. Crawford DK, Mangiardi M, Xia X, López-Valdés HE, Tiwari-Woodruff SK. Functional recovery of callosal axons following demyelination: A critical window. Yoga and generalized anxiety disorder (GAD) Neuroscience 2009;164:1407-21. Not many studies are reported on GAD. However, a study 3. Wagner EH. The role of patient care teams in chronic on the analysis of effect of Sudarshan Kriya Yoga (SKY) on disease management. BMJ 2000;320:569:72. GAD reports symptomatic improvement in the cases.[22] 4. Mozaffarian D, Fahimi S, Singh GM, Micha R, Khatibzadeh S, Engell RE, et al. Global sodium consumption and death from cardiovascular causes. N Engl J Med 2014;371:624-34. FUTURE PROSPECTS IN THE ROLE OF 5. Global Status Report on Alcohol and Health; 2014. YOGA FOR ND 6. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair-Rohani H et al. A comparative risk assessment Yogic exercises recharge the body with cosmic energy and of burden of disease and injury attributable to 67 risk facilitate body to improve psychological/mental well-being. factors and risk factor clusters in 21 regions, 1990-2010: Yoga helps with anxiety and depression. It boosts memory A systematic analysis for the Global Burden of Disease and improves concentration and prevents the onset of mental Study 2010. Lancet 2012;380:2224-60. health conditions, which are prevalent during adolescence. 7. Caulfield AF, Wijman CA. Management of acute Yoga reduces the effects of traumatic experiences also. ischemic stroke. Neurol Clin 2008;26:345-71. A review of numerous studies employing Yoga in healthy 8. WCN 2015: Changing Neurology Worldwide. Santiago, volunteers and patients reveals that eliciting relaxation Chile: WCN; 2015. through mediation is very beneficial. Yoga promotes positive 9. Ishwar V. Basavaraddi Yoga: Right path to health and effects on carotid atherosclerosis, hypertension, diabetes, and wellness. Yojana 2015;59;7-12. coronary artery disease (which are also identified risk factors 10. Rajesh B, Jayachandran D, Mohandas G, associated with stroke) and a number of psychological Radhakrishnan K. A pilot study of a yoga meditation problems. Thus, future prospect lies in harnessing the protocol for patients with medically refractory epilepsy. potential of Yoga for the prevention of NDs by sensitizing J Altern Complement Med 2006;12:367-71. and familiarizing the practice of Yoga. 11. Lundgren T, Dahl J, Yardi N, Melin L. Acceptance and commitment therapy and yoga for drug-refractory epilepsy: A randomized controlled trial. Epilepsy Behav DISCUSSION AND CONCLUSION 2008;13:102-8. 12. Panjwani U, Selvamurthy W, Singh SH, Gupta HL, In the present era, where everything turns from natural to Mukhopadhyay S, Thakur L, et al. Effect of sahaja artificial, communities want to go back in the natural life yoga meditation on auditory evoked potentials (AEP) where they need safe, effective health care and here starts and visual contrast sensitivity (VCS) in epileptics. Appl the role of Yoga. The holistic wisdom of Yoga offers the Psychophysiol Biofeedback 2000;25:1-2. necessary wisdom, experience, and capabilities those are 13. Naji-Esfahani H, Zamani M, Marandi SM, crucial for such transformation. Studies have proved Yoga Shaygannejad V, Javanmard SH. Preventive effects of a to be beneficial in the management of various neurological three-month yoga intervention on endothelial function in disorders. It has soothing, calming, and balancing effects patients with migraine. Int J Prev Med 2014;5:424-9. on the brains, nerves, and autonomic nervous system 14. Cramer H, Lauche R, Langhorst J, Dobos G. Yoga for regulation. Yoga - asana, pranayama, and dhyana have depression: A systematic review and meta-analysis. immense potential for the prevention of neurological. Yoga Depress Anxiety 2013;30:1068-83. develops our personality in a holistic and balanced way, 15. D’Silva S, Poscablo C, Habousha R, Kogan M, Kligler B. transform the youth in leading a healthier, and stress-free Mind-body medicine therapies for a range of depression life. Steps - regular daily practice, incorporation in schools, severity: A systematic review. Psychosomatics etc., should be incorporated to reduce the global burden of 2012;53:407-23. diseases, not only NCDs. Thus, Yoga as science of holistic 16. Orig. book by Eudora Seyfer, Lorna Bell. Gentle Yoga: living can improve the general well-being of individuals and A Guide to Low-Impact Exercise, Celestial Arts; 1990. societies and proving to be the most desirable complimentary p. 4-11 and traditional system of health care in the present scenario. 17. Lynton H, Kligler B, Shiflett S. Yoga in stroke

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rehabilitation: A systematic review and results of a pilot tsunami. Acta Psychiatr Scand 2010;121:289-300. study. Top Stroke Rehabil 2007;14:1-8. 21. Telles S, Singh N, Joshi M, Balkrishna A. Post-traumatic 18. Garrett R, Immink MA, Hillier S. Becoming connected: stress symptoms and heart rate variability in Bihar flood The lived experience of yoga participation after stroke. survivors following yoga: A randomized controlled Disabil Rehabil 2011;33:2404-15. study. BMC Psychiatry 2010;10:18. 19. Cramer H, Lauche R, Klose P, Langhorst J, Dobos G. 22. Katzman MA, Vermani M, Gerbarg PL, Brown RP, Yoga for schizophrenia: A systematic review and meta- Iorio C, Davis M, et al. A multicomponent yoga-based, analysis. BMC Psychiatry 2013;13:32. breath intervention program as an adjunctive treatment 20. Descilo T, Vedamurtachar A, Gerbarg PL, Nagaraja D, in patients suffering from generalized anxiety disorder Gangadhar BN, Damodaran B, et al. Effects of a yoga with or without comorbidities. Int J Yoga 2012;5:57-65. breath intervention alone and in combination with an exposure therapy for post-traumatic stress disorder and depression in survivors of the 2004 south-east Asia Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S230 Significance of Yoga postures on the Marmas

Vijay Laxmi Gautam Department of Rachana Sharir, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

Abstract

The science of Marma is another extraordinary and dynamic Àyurvedic therapy that has tremendous value in health and disease everyday living and spiritual practice. The term “Marma” literally communicates to vulnerable parts or areas of the body. “Marma is the seat of life” Marma therapy - the art of treating specific vital points on

REVIEW ARTICLE REVIEW the human body is one of the greatest healing systems of Yoga, i.e., the state of consciousness where the mind comes to silence, then can the seer experiences his own nature. Otherwise, its true nature is overshadowed by the activity of the Mind1. Yoga is a philosophical system that has been in existence for thousands of years and like Àyurveda, originates from the Veda. However, Yoga is a comprehensive approach to self-discovery and includes behavior, nutrition, ethics and morality, and above all meditation. Through meditation the mental approach of Yoga that is using the mind, we experience rest in the body as well as silence in consciousness. The path of Yoga leads to the self the Àtma, the basis of all Marmas. Through Yoga, we comprehensively harmonize and strengthen the secrets of Àyurveda. This article purpose is to review the important key functions of Yoga and its effect.

Key words: Consciousness, healing, Marma, mind, Yoga postures

INTRODUCTION Naturally, Marma science has influenced all other sciences which we find in vedas such as Yoga, Àyurveda, Dance, he term “Marma” literally communicates Music, Mantra, Martial arts, Astrology, Philosophy, and to vulnerable parts or areas of the body. Siddha system of medicine and sexology. The development Any trauma on the Marma region may of this science took place from Saraswati culture to the time T period of Caraka, SuÒruta, AÒtaÁng hªdaya and sa¿graha cause loss of function of that organ or site, and even death may occur depending on the site and and later on Buddha religion was responsible for its spread in [4] strength of the trauma. The knowledge of the the neighboring countries such as China and Japan. surgery forms its foundation through anatomy, and meticulous dissection of human body can develop Àyurveda is India’s traditional healing system and a profound perfection in anatomy that consequently develops system of mind-body medicine and natural living. Àyurveda enhanced and improved surgical maneuver. which means “the science of life” has become recognized today for its wonderful dietary, herbal lifestyle and yogic Marma science is the part of vedic science. therapies that help us live longer, happier, wiser, and more in Knowledge of Marma exists from very ancient harmony with the greater universe of life and consciousness. time of vedas, which dates back to 4000 B.C. The Maharshi Sushruta was pioneer of surgery. The Marma [1] have been included in Sushruta samhita Sharir sthana sixth first reference is found in égveda. In Atharva- [5] veda also we find the reference of the term kavacha chapter in “Pratyeka Nirdesha Shareeram.” or corselet for protection of chest.[2] Mahabharat Agnive Ðha (3000 B.C.) first discovered the existence was the biggest war recorded in the history of of 107 Marmas which are anatomical sites or vital spots India. The weapons were in the form of arrows and sword. The time moved forward, and the arrows and swords converted into high-speed bullets Address for correspondence: Dr. Vijay Laxmi Gautam, Department of Rachana Sharir, that are more hazardous. The bullets and firearms Faculty of Ayurveda, Institute of Medical Sciences, required major surgical interference where extreme Banaras Hindu University, Varanasi – 221 005, care is required, if Marma points are involved. The Uttar Pradesh, India. Phone: +91-9451440263. warriors and soldiers when get wounded in such E-mail: [email protected] battles or today’s getting injured.[3]

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(four extremities, thorax, abdomen, back and head-neck) In Kshurikopanishad, the word Marma is used in connection are present within the body. Charaka Samhita, the most with the description of the quality of knife, which is as strong ancient treatise on medicine, states that among 107 Marmas, as of Indra vajra and capable of cutting a vital part (Marma) only three Marmas are of great importance and for clinical of jangah.[10] significance; they are MurdhÁ (head), Hªdaya (heart), and vasti (urinary bladder).[6] Marma and Siddha System

According to Siddha System, the entire universe is originated REVIEW OF MARMA from the union of Lord Shiva- Matter and his wife, Parvati- energy. Logically, Shiva itself represents both matter and “Mri- manin-jeevsthane, Sandhi sthane, tatparye ch|” energy; the Shiva is originated from Vasi, which means (Shabdastoma) breathing. It is very similar to Ayurveda, that union of matter and energy is responsible for the formation of five primordial The term Marma has its origin from the Sanskrit root word elements. In this system, all the Marmas are invisible but “Mri” denoting the meaning of vital parts. The word Marma could be traced or located at the point where body, mind, is used in the sense of jeevsthana (seat of life), Sandhisthan and psychic energies are concentrated together. The Marma [7] (joints), and tatparya. is nothing but blockage of vital energy (Vasi) in the body. The blockage could be due to - external physical injuries, “Mri- sarvadhatubhyo manin eti Marma| Sannipata psychological passions, and their effects through doshas. Therefore, Marmas can be controlled by psychic powers. Shira-snayu-sandhimamsa-asthi sambhava.” (Halayudha These points are called as “maitheenda kalam.”[11] kosha)

In Halayudha kosha the term Marma is defined as a Marma and Yoga combination of Sira (veins), Snayu (ligaments), Sandhi (joint), mamsa (muscle), and Asthi (bone). The science of Yoga explained by great sage PÁtanjali in his “Yoga sutras.” Àyurveda is the science of life/longevity, The Shabdakalpadruma also favors the description of and Yoga is the science of linking the individual self with the Halayudha kosha in the context of the term “Marma.” universal self. Both sciences Àyurveda and Yoga have been evolved from the same philosophy, culture, and country. The In Sanskrit dictionary of Monier-William and MacDonnell, Yoga and yogic postures/Ásanas tries to expand the narrow etymologically the word Marma denotes mortal spot, constricted egoistic personality to the all-pervasive, eternal vulnerable point, weak/sensitive point of the body or secret, and blissful state of reality. There are various types of Yoga mystery, and excessively painful.[8] practices: The Hatha Yoga, RÁja Yoga, Bhakti Yoga, DhyÁna Yoga, Mantra Yoga, Karma Yoga, etc.[12] The Hatha Yoga According to Dalhana, “Marma” letter “Ma” denotes the (much popular) explains that there are six (MulÁdhÁra, prana, and the word “Ra” denotes the location or seat. SwÁdhisthana, Manipura, AnÁhat, Vishuddha, and Ajña) Hence, the word Marma means the place where the pranas chakras-(nerve plexus), which are distributed throughout are located or situated. the body in addition to the main brain center called the Sahashraras. The sahashrÁra chakra is situated in the brain, “Api ch maramkaritvan Marma|” (As.Sa.Sh. 7/13) and it has been described in yogic texts as having a thousand and one petals. These chakras are connected by nÁdis or “Vishamam spandanam yantra pidite ruk ch Marma tat|” channels to different organs in the body. The Siddha system (As.Hr.Sh. 4/9) is very similar to that of Àyurveda and amalgamated the principles of Àyurveda and Yoga together.[13] Which leads to causes of death is designated as Marma. In Marmas are like batteries, they become charged by Yoga postures other context, with a view to make the concept of “Marma” and movement that is performed correctly. With smooth flowing more generalized that which causes death is called Marma.[9] movements, gentle stretching and finally the restful position at the end of each Asana, the natural flow of energy is supported in The first reference is found in égveda for the Marma. the subtle energy channels of the body, the NÁdis.[14] Marmani te vermanacha dayami, somsattva rajamritenanuvastama| (Rgveda 6:6:75) Marma in Samhitas

In Garbhopnishada, 107 Marmas are described. In Charaka, Sushruta, and Vagbhata Samhita are three major Yogopnishada, 18 Marmas of the body are described on treatises mentioned as references Ayurveda. Acharya Charaka which by concentration one can practice dharana. sited important, consequential Marma from the physician

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S232 Gautam: Significance of Yoga postures on the Marmas point of view for but acknowledged by 107 Marmas in the c. Bahu (Upper extremity – 22, body. He described in his treatise two chapters on Trimarma d. Pªustha (Back) – 14, (Hridaya, Shir, and vasti) and in chikitsa sthana and another e. Jatru-Uªdhva (Above Clavicle) –37. in Siddhi Sthana. According to Size- (Anguli Pramana) Marmas situated in trunk region are comparatively more a. One fingerbreadth, important than Marmas of Shakha Acharya Charaka b. Two fingerbreadth considered these three Marmas are in ten pranayatana, c. Three fingerbreadth i.e. Murdha, Hridya, Vasti, Kantha, Shonit, Shukra, Oja, d. Fist size or four fingerbreadth, Guda, Nabhi, and Mamsa.[15] e. One and half fingerbreadth. Marma in Sanskrit means hidden or secret. By definition, a Based on Prognosis (when injured) Marma point is a junction on body where two or more types of tissue meet, such as (Mamsa-Sira-Snayu-Asthi-Sandhi) a. Sadyha PrÁnahara Marma (instantly fatal) - 19, muscles, veins, ligaments, bones, or joints. b. KÁlÁntara PrÁnahara Marma (gradually fatal) - 33, c. ViÐalyaghna Marma (fatal on extraction of foreign MaharÒi SuÒruta was pioneer of surgery. Marma in Sanskrit body) - 03, means hidden or secret. By definition, Àcharya SuÒruta defines d. Vaikalyakara Marma (causes disability) - 44 Marma point is a junction as well as the anatomical site where e. RujÁkara Marma (painful) - 08. muscles (MaÞsa), blood vessels (Sira), ligaments (Snayu), bones (Asthi), and joints (Sandhi) meet together. Marmas are Fatal Period of Marma specially seats of the concentration of prÁnic currents by virtue of their nature. Therefore, any injury to any Marma invariably The prognosis of the Marma is variable depending on the produces characteristics features. (Su Sh.6/22),[16] Àyurveda is intensity of trauma, the type of weapon used, and the depth of a part of the older spiritual heritage of humanity that contains the wound and the loss of type of tissue. According to Sushruta secret knowledge and profound wisdom. The Marmas are and other ancient scholars that fatal period of Sadhya Pranahara certain vital points or places where the prÁna (life force) is said Marma in 7 days; The KÁlÁntara PrÁnahara Marma bears to be situated. The Marmas, definition of Marmas, and their 15 days or 30 days and Vishalyaghna Marma and Vaikalyakara treatment are described by nearly all Àyurvedic texts especially Marma sometimes causes death when greatly injured.[18] “Trimarmiya Siddhi,” “Trimarmiya Cikitsa” chapters in Caraka SaÞhita, “Marma Vibhaga” chapter in AÐtÁnga SaÞgraha, and [17] The word Marma comes from Sanskrit origin word “Shareer Vicaya Sharir” chapter in KÁshyapa SaÞhita. In “méi” meaning death. The Sanskrit phrase, “MÁryante Iti Àyurveda, a 107 points Marmas system was developed by the MarmÁni,” also means death or serious damage to body or ancient Indian surgeon Susruta for helping a surgeon to safely health after infliction to the point of their situation. Hence, operate on the human body. these areas are called Marma. In Siddha system of medicine, they are called Varma.[19] Àcharya SuÒªuta (1000 B.C.) has been realized the separate surgical values of all 107 Marmas and describing them by Yoga is a philosophical system that has been in existence for giving their classification, measurement, effect of injury, thousands of years and like Ayurveda, originates from the Veda. surgical importance, and clinical instructions in details. Yoga keeps us young and fit, gives us new energy and refines our perception of the energies of our mind and body and the Classification of Marmas silent intelligence that underlies nature and cosmos. The best time for Yoga is when you have some peace and quiet for the Àcharya SuÒruta describes that 107 anatomical locations practice hence in the morning before breakfast or in the evening known as Marmas. These are of some types as under given: before dinner. There are different schools of Yoga, which often have quite different views on the selection of Ásanas, the nature Structural Classification of their executions and the aim of exercises. The proper exercise of Ásanas stimulates, opens and strengthen different Marmas a. Ma¿sa Marmas - 11, depending on the body postures and movements. b. Sira Marmas - 41, c. Snayu Marmas - 27, d. Asthi Marmas - 08, e. Sandhi Marmas - 20. ROLE OF MARMA There are three basic purposes of Marma: Regional Classification 1. It removes blocks in energy channels called shrotas. a. Sakthi (Lower extremity) – 22 2. It pacifies vÁta doÒha, (air and space elements), b. Ura and Udara (Thorax and Abdomen) - 12 bringing it to its normal path - especially vyana vÁta,

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(a sub- doÒha which controls the autonomic nervous the functions of a Marma. In some VÁta is predominant, system) for example, in Marmas located in the joints. Their job is 3. It creates physical, mental and emotional flexibility. to control and coordinate motion and orientation in space. Because of Áma (toxins) and because of Vata, human Marmas ruled by pitta are responsible for metabolism and beings after 35 or 40 years of age become rigid - and this the generation of energy and heat. Kapha Marmas provide happens to animals and plants as well. As vÁta increases stability and endurance, maintain the physical structure.[21] in the body, it leads to degeneration. This rigidity means becoming fixed in ideas, emotions, and physical movements.[20] Tissue Types in Marma

The study of Marmas point and effect of Yoga posture can be Àyurveda divides body tissue into seven basic structure summarized to the following points. patterns. Some have more effect on plasma and lymph, others on blood, muscle, adipose tissue, bone, and the supporting tissues of the body. Principal Marma Points Centre

Marmas are not the anatomical structures - they are areas in The Five Elements of the Marmas anatomy where consciousness connects with the body and coordinates its functions or to put in another way, Marmas are All five elements are generally represented in each Marma, the places where the intelligence transforms into matter, into but one or two may predominate depending on the type of the body. This means that all the information of one Marma Marma. Fire Marmas warm or heat up. When treating them, is also present in all the others. Since a Marma is more of we feel a sensation of heat or warmth that even spreads along an area than a single point, it often includes several smaller the corresponding energy channel. There are also cooling Marmas and then acts as a coordinating center, monitoring all Marmas where water is the dominant element. When the the signals emanating from the smaller points. Furthermore, element of air or space dominates in a Marma, then it is several meridians (called NÁdis in Àyurveda) always merge particularly sensitive and alert and controls movement, as in with the main Marma which acts as a reservoir of energy. the joint Marmas. Where the earth element predominates, it provides stability.[22] The Marma House

A Marma is like a house in which all the residents have DIFFERENT YOGA ÀSANAS: SET FOR their own rooms and tasks. Here again, we find the all ALL MARMA Àyurvedic principles; the three DoÒas as bioregulators, the five elements as components of the Marmas, the metabolic In India, traditional food consists of six tastes, sweet, sour, energy agni, the happiness and nutrient substances Ojasa, the pungent, astringent, bitter, and salt. A lot of Indians say seven types of DhÁtus (tissue), and the mental characteristics that when sitting down to eat, the stomach gets pressed and (Sattva, Rajas, and Tamas). They all indicates the individual digestion is stimulated. activity of the field and significance of a Marma, and on this basis, we can make a meaningful classification of Marmas.[22] In Marma SÁshtra, NÁbhi Marma (navel point), and Bªihati Marma (sides of the shoulder blades) are important yogic points for better acid secretion. This increases digestive fire, Marmas and Three Doñhas detoxification, reducing Áma (toxins), promotes energy, and The three main Marmas are closely related to the three rejuvenation. Proper digestion leads to good utilization of DoÒhas (bio-regulators) which also have their principal seat food and better absorption of nutrients. This is a good cure in the same regions. Though all aap (Kapha), vayu (Vata) and for even obesity when samÁna vÁyu (balanced air for better agni (Pitta) are present in Marmas. It is due to predominance bowel moments) has to be maintained. If it is not in balance, of agni are called as agneya in nature. The particularly agni the stomach would bulge; this shows samÁna vÁyu imbalance and vayu (Pitta and Vata) are responsible for pain but aap in the solar plexus (Manipura Chakra). (Kapha) also does it as pain and observed in kaphaj wound. The three DoÒhas are like a (musical) triad in the personality. Postures such as Yoga Mudra, PavanamuktÁsana, When they are in balance, they create a unified togetherness, a DhanurÁsana, and Ardha MatsyendrÁsana can stimulate this mental and physical harmony, making us feel happy, powerful Point. Breathings such as KaphÁlabathi and BastrikÁwould and full of positive energy and enthusiasm. If, however, one also stimulate this point. Even practices such as Nauli, and DoÒha is out of tune like one string of an instrument, then UddiyÁna BÁndha can stimulate it and eliminate excess disharmony is created. With the continued imbalance of gases. This NÁbhi Marma becomes a trigger point for Dosha, physical and mental symptoms arise resulting in what Manipura chakra where crystal healing and reiki healing can we commonly call diseases. The three Doshas characterize be done to balance the energy in these chakras.[26]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S234 Gautam: Significance of Yoga postures on the Marmas

If you are a beginner and are learning the Àsanas for the first and collects in the Pituitary gland and the third eye (Sthapani time, then do not pay attention to every detail of each posture Marma). The Guda Marma is addressed by the pressure of make sure that you do not involuntarily hold your breath. Do the heel and the Marmas of the lower back by stretching. It is not worry about practicing the Àsanas perfectly, just take also a beneficial exercise for Brihati Marma which is gently it easy and start at a point. If you do it right, then you will stretched and charged. The physical contact of JÁnu Marma notice that your inward and outward breathing will initiate also has a soothing effect on Sthapani and promotes inner the outward and inward movements of Àsanas. silence and concentration in resting position.[24]

Become Aware of Oneself Shoulder stand – Sarv Ángasana

Bringing the attention back to the body has a calming and In Sarvangasana or shoulder stand asana many variations of balancing effect on all the Marmas and stimulates the flow the shoulder stand exist, the likely most common to be taught of energy in the NÁdis. Sit comfortably, direct your attention is supported shoulder stand. Sarvangasana is nicknamed inward and let your body and mind come to rest.[25] “queen” or “mother” of all the asanas. By compressing the anterior neck and increasing blood pressure in the head, the Enlivening Exercise – Samvahana neck and head Marmas are particularly stimulated Adhipati and Simanta included. The hands and their Marmas come into physical contact with the entire body and bring lymphatic and other fluids Cobra – Bhujang Ásana and energies to the heart. Almost all the Marmas are gently massaged in the direction of the heart, starting at the forehead The stretching of the neck opens the throat Marmas and the and face and proceed downward. expansion of the chest Marmas. The Lumbar and Gluteal muscle are contracted, and therefore the Marmas in this [24] Rolling – Vellan region are stimulated.

It is relaxing and loosening especially on the Marmas of the Locust – Shalabh Ásana spine and the muscles of the back. Hold your knees with clasped hands and breathe in. As you exhale slowly roll to In this posture, the Lohitaksha and Vitapa Marmas are opened the side and stay there for a moment, as you then inhale roll and vitalized by the stretching in the groin area. The tension [24] back finally exhale again and roll to the other side. in the buttocks and the Lumbar muscles stimulates all the Marmas of the pelvis and the lower back.[25] Diamond Posture – Vajr Ásana Bow – DhanurÁsana This posture increases self-confidence and strengthens the back, clarifies the mind and opens the chest and the breathing. In this posture, the groin region Marmas Lohitaksha and It also opens Gulpha and other Marmas. It reduces tension Vitapa, in particular, are stretched and freed of tension. in the extensor muscles of the legs and facilitates the flow Furthermore, the ankle Marma, Gulpha and thigh Marmas of energy in the NÁdis of the spine up to the head Marmas. are opened. In contrast, the Marmas of the whole back are The Gulpha, the ankle Marma on foot, is opened by the strengthened by the muscular tension and the position of the stretch and stimulation by the gentle pressure of the weight spine while the Marmas of the chest are enlivened through of the body. The counterpart of Indrabasti on the extensor stretches. The abdominal (Ura and Udara) Marmas are also side of the lower leg is also stretched and opened, as also in stimulated by rolling on the floor. Janu, the knee Marma. The Talahridaya of the hand is on the Àni Marma on the thighs. It strengthen and soothes it, and in addition the stretching of the knee also opens the Àni Half spinal Twist – Matsyendry Ásana Marma. The energy in the spinal cord, NÁdis Ida, Pingala, and SuÒumna can flow freely then. The rotation of the spine and stretching of all the muscles of the trunk massages the internal organs and stimulates all Sitting Forward Bend – Janu Shirshana the Marmas of the back, abdomen, and chest. In addition, the Marmas of the arm, Manibandha, Indrabasti, Kurpara, The forward bend stretches and relaxes the lower back which Àni, Uªvi, LohitÁksha, and KakshÁdhara are involved makes energy flow into the pelvic area and especially into the when the arm supports the posture. The half spine twist root Chakra and Guda Marma. In the movement sequence, all promotes elasticity of the spine and prevents the sciatica the back Marmas are opened from bottom to top. In the restful and muscular discomfort in the legs while internal organs end position, the SuÒumna energy starts flowing upwards such as the liver, spleen, pancreas, urinary bladder, kidneys,

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S235 Gautam: Significance of Yoga postures on the Marmas and adrenals are compressed and massaged and increase 7. Published by Chow Chambha Sanskrit Series Office. blood flow.[24] Shabda Stom Mahanidhi (Sanskrit Dictionary) Compiled by Tarka Vachaspati Tarachand Bhattacharya. Varanasy: Standing Forward Bend – UttÁnasana Published by Chow chambha Sanskrit Series Office; 1967. The increased blood flow to the head addresses all the 8. Druma A. Raja Radhakant Dev. New Delhi-7 (India): head Marmas (Vidhur, Phana, Àwarta, Shankha, Utkshepa, Nag Publishers; 1987. Sthapani, SÍmanta, ShrangaÔaka, and Adhipati), and all 9. Sangraha VA, Àcharya SS. Shashilekha Sanskrit the back Marmas (KaÔÍktaruna, Kukundara, Nitamba, Commentary. 1st ed. Varanasi, U.P. India: Caukhambha PÁrÐhva-sandhi, Vªihati, AÞshaphalaka, and AÞsha) are Series office Publication; 2006. stretched and opened. The process starts with feet together 10. Trivedi EP. Rgveda, Pt. Govind Nath. Chowkhambha and hands by the sides of the body (Samasthiti). Inhale, raise Vidyabhawan, I-IX Part. Varanasi: Chowkhambha and stretch both arms above the head keeping them shoulder- Orientalia Series; 1991. width apart, Bend the head, arms and the upper trunk slightly 11. DS, A. Secrets of Marma (A Comprehensive Textbook backward and stay for a few breaths, exhale, and come back of Ayurvedic Vital Points). Pune; International Acadmey to Samasthiti.[23] of Ayurveda; 1999. p. 13. 12. Darshanam PA. Swami Aari Haranand Aaranya. Varanasi: Motilal Banarasidas; 1987. CONCLUSION 13. Schrott E, Raju JR, Schrott S. Marma Therapy, Translated by Marek Lorys Singing Dragon. London The Marma points can be treated in very different ways. and Philadelphia, Pa: Mosaik Veriag, Munich, Germany; There are many ways to treat the Marmas such as pure 2009. attention without touching, touching with attention, oil baths, 14. Ða A. Caraka Samhita, Ayurveda Dipika commentary of basti, aromatherapy, vedic ceremonies to strengthen positive Cakrapanidatta, Ed. Yadavji Trikramji. 5th ed. Bombay: influences, and breathing exercises: Pranayama and Yoga Acharya Ninmaya Sagar Press; 2001. p. 645. exercises: Àsanas.[23] The physical Yoga exercises and its 15. Ghanekar BG. Sushruta Samhita, Ayurvedarahasya Ásanas give the Marmas room to breathe. They reconnect the Dipikakhtya, hindi Commentary. Ansariroad, Dariya Marmas with the state of unity, the inner self, the Átma. When Ganj, New Delhi, Reprint: Mehar Chand Laxman Dass they are reconnected in this way the Marmas are enlivened, Publication; 2008. p. 1. they expand and can fully express their inner qualities. Yoga 16. Ða A. Caraka Samhita, Ayurveda Dipika commentary of Ásanas charge the Marmas with energy and support physical Cakrapanidatta, Ed. Yadavji Trikramji. 5th ed. Bombay: and mental reprocessing of the pattern of experience stored Acharya Ninmaya Sagar Press; 2001. p. 649. in the Marmas, in addition, certain finger postures or Mudras 17. Vagbata, Ashtanga Sangraha; Àcharya SS. Shashilekha can be used to harmonize the Marmas.[23] Sanskrit commentary. 1st ed. Varanasi, U.P. India: Caukhambha series office Publication; 2006. SaÞhita K, Tantra V. English Translation and Commentary by P. V. REFERENCES Tiwari, Caukhambha. Varanasi: Vishvabharti; 1996. 18. Ghanekar BG. Sushruta Samhita, Ayurvedarahasya 1. Trivedi EP. Rgveda, Pt. Govind Nath. I-IX Part. Dipikakhtya, hindi Commentary. Ansariroad, Dariya Varanasi: Chowkhambha Vidyabhawan; 1991. Ganj, New Delhi, Reprint: Mehar Chand Laxman Dass 2. SaÞhita A. (Translated in English by) William Dwight Publication; 2008. p. 1. Whitney. In: Lammon CR, editor. Varanasi, New Delhi, 19. Apte VS. The Student English Dictionary. Jawahar Nagar, Patna: Motilal Banarasidas; 1984. New Delhi, India: Nag Publishers; 1993. p. 7. 3. Dutt MN. The Mahabharat, Translated in English Ed. 20. Published by International Academy of Ayurveda. Yoga (Shastri) New Delhi: H.C.Dass, Stanford Library; 1988. Sutra of Patanjali-by Mukunda. Pune, India: Published 4. Frawley D, Ranade S, Lele A. Secrets of Marma (A by International Academy of Ayurveda; 1998. Comprehensive Textbook of Ayurvedic Vital Points). 21. Schrott E, Raju JR, Schrott S. Marma Therapy, Pune: International Acadmey of Ayurveda; 1999. p. 10. Translated by Marek Lorys Singing Dragon. London 5. Ghanekar BG. Sushruta Samhita, Ayurvedarahasya and Philadelphia, Pa: Mosaik Veriag, Munich, Germany; Dipikakhtya, hindi Commentary. Ansariroad, Dariya 2009. p. 16. Ganj, New Delhi, Reprint: Mehar Chand Laxman Dass 22. Schrott E, Raju JR, Schrott S. Marma Therapy, Translated Publication; 2008. p. 1. by Marek Lorys Singing Dragon. London and Philadelphia, 6. Ða A. Caraka saÞhita by Kashinath Shastri and Caturvedi. Pa: Mosaik Veriag, Munich, Germany; 2009. p. 19. 4th ed. Varanasi: Caukhambha Sanskrit Sereies Office; 23. Schrott E, Raju JR, Schrott S. Marma Therapy, Translated 1994. by Marek Lorys Singing Dragon. London and Philadelphia,

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Pa: Mosaik Veriag, Munich, Germany; 2009. p. 111. Pa: Mosaik Veriag, Munich, Germany; 2009. p. 123. 24. Schrott E, Raju JR, Schrott S. Marma Therapy, 26. Schrott E, Raju JR, Schrott S. Marma Therapy, Translated Translated by Marek Lorys Singing Dragon. London by Marek Lorys Singing Dragon. London and Philadelphia, and Philadelphia, Pa: Mosaik Veriag, Munich, Germany; Pa: Mosaik Veriag, Munich, Germany; 2009. p. 122. 2009. p. 124. 25. Schrott E, Raju JR, Schrott S. Marma Therapy, Translated by Marek Lorys Singing Dragon. London and Philadelphia, Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S237 Non-communicable diseases: A review on the current role and future prospects of yoga

Vijay Kumar Rai1, Shalini Rai2 1Department of Swastha vritta and Yoga, Government Post - Graduate Ayurveda College and Hospital, Sampurnanad Sanskrit University, Varanasi, Uttar Pradesh, India, 2Department of Roga Nidanevum Vikriti Vigyan, All India Institute of Ayurveda, Sarita Vihar, New Delhi, India

Abstract

REVIEW ARTICLE REVIEW Non-communicable diseases are fastest growing public health problems in the world; these conditions are difficult to treat and expensive to manage because these are chronic diseases or diseases of long duration and generally slow progression. Cardiovascular diseases, chronic respiratory diseases, diabetes, and cancer are topmost killers in the South-East Asia sphere, claiming an approximated 8.5 million lives each year. Fortunately, because the causative factors are modifiable, disease manifestation from these factors is largely preventable. Less physical activity and stress are the major factors now linked to a wide range of Non-communicable diseases. It is now well recognized that less physical activity and stress weakens our immune system and threshold of our body. Scientific research in several recent studies has shown that the yoga practices have the good impact on physical, physiological, psychological, and biochemical changes in the human body, yoga practices are of anti-stress in nature. Various yoga practices can be of great help in not only preventing but also controlling non-communicable diseases.

Key words: Control, non-communicable diseases, prevention, yoga

INTRODUCTION practices are of anti-stress in nature. The WHO[2] has been advocating yoga as one of the effective therapeutic system on-communicable diseases are fastest and yoga is believed to offer means for the actualization of growing public health problems in the human potential to perfection through its three‑dimensional Nworld; these conditions are difficult to approach to health – physical, mental, and spiritual. Various treat and expensive to manage because these are yoga practices can be of great help in not only preventing but chronic –diseases or diseases of long duration also controlling non-communicable diseases. and generally slow progression. The WHO[1] stated that cardiovascular diseases (CVD), Yoga is finding an increasing approval as a non- chronic respiratory diseases, diabetes, and pharmacological intervention for the prevention and treatment cancer are top killers in the South-East Asia of diseases. A peaceful mind is conducive to healing and Region, claiming an estimated 8.5 million lives happiness is now accepted by the contemporary medicine each year. Fortunately, because the causative science. They have also started recognizing the effects the factors are modifiable, disease manifestation psyche has on the soma and have integrated the concept in from these factors is largely preventable. the fields of psychoneuroimmunology. This is the reason Less physical activity and stress are the major modern medical science is also accepting the importance of factors now linked to a wide range of non- peace, joy, love, positive thinking,[3] relaxation, hope, etc., communicable diseases.

It is now well recognized that less physical Address for correspondence: activity and stress weakens our immune Vijay Kumar Rai, system and threshold of our body. Scientific Department of Swastha vritta and Yoga, Government research in several recent studies has shown Post - Graduate Ayurveda College and Hospital, that the yoga practices have the good impact Sampurnanad Sanskrit University, Varanasi – 221002, on physical, physiological, psychological, and Uttar Pradesh, India. biochemical changes in the human body, yoga E-mail: [email protected]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S238 Rai and Rai: Yoga: the restraint for non-communicable diseases and accepting them as therapeutic tools. Yoga integrates and emergence of psychoneuroimmunology.[6] Although these effects in the practitioner by helping the individual to these emotions cannot be quantified, their effect on body reconcile with the self and various situations and lead total system can be assessed to some extent by measuring certain health to the individual and peace and happiness globally. biomarkers such as cytokine levels or measurement of natural killer cells. Science quests for quantifiable evidence. Based on the above rationales, yoga has been utilized in Providing substantiation for the effects of emotions on the management of some non-communicable diseases. This biological responses may prove to be a great significance to paper presents the scientific studies with the aim to highlights the health and disease. The evidence spawned has made the the importance and role of yoga in the current time to have contemporary science accept the positive emotions, positive an approach toward complete therapy and to utilize yoga thinking, relaxation, hope, etc., as therapeutic tools. The therapy in non-communicable diseases. acceptability of yoga as a potent instrument for influencing the mind positively is based on the lines of above-mentioned mechanisms.[7] REVIEW METHODOLOGY

The electronic databases of Google Scholar, PubMed, and YOGA IN OBESITY AND Scopus were searched with the various combinations and CARDIOVASCULAR DISEASE permutations of the keywords “yoga, non-communicable diseases, prevention, management, cardiovascular disorders, Obesity has been researched extensively, and it has been obesity, hypertension, cancer, diabetes mellitus (DM), and revealed that a state of low-to-mild grade of inflammation scientific researches.” English language abstracts and full- is associated in it which may lead to the development of text articles were considered for the review and saved to a number of chronic diseases.[8] Studies have suggested a folder. The matter was then analyzed and presented in a evidence for the contributory role of inflammation in the systemic manner. causation and progression of CVD. The current approach focuses on pharmacological management, weight reduction along with attention on nutritional interventions and increased THE THERAPEUTICS OF YOGA physical activity.[9] Scientific studies have shown that lifestyle intervention has a very promising role in patients with CVD Yoga is though not a therapeutic tool but the practice of yoga or those at an increased risk of CVD.[10] Therefore, lifestyle brings about various changes in the human body. Some of the modifications the practice of yoga have a very specific role in important changes observed and documented by the scientists the management as well as in the prevention of these diseases. through researches are improved cognitive functions, alteration in brain blood flow and brain metabolism, Many studies have tried to explore the mechanisms by which modulation of the neuroendocrine axis, harmonious yoga modifies the risk factors for coronary artery diseases. balance of autonomic function, increase in alpha rhythm, Ornish et al., Manchanda et al. and Yogendra et al. have interhemispheric coherence and homogeneity in the brain, angiographically proven though prospective, randomized, improved sleep quality, improvement in cardiorespiratory and controlled trials that CAD patient with yoga-based efficiency,[4] improvement in exercise tolerance, improvement lifestyle modification helped in the regression of coronary in agility, strength, stability, endurance, flexibility, tenacity, lesions and improvement in myocardial perfusion. and neuromusculoskeletal coordination.[5] Further, a review investigating the effects of yoga on risk Various postulates have been described for explaining indices associated with insulin CVD, resistance syndrome, the mechanism of action of yoga and its benefits such and possible protection with yoga reported that most of as restoration of autonomic balance, improvement in the the participants had a reduction of systolic and/or diastolic capacity of rehabilitation and regeneration and overall anti- blood pressure (BP).[11] Even short-term yoga‑based general stress effect on the individual. A theory proposed by Streeter lifestyle intervention led to a remarkable reduction in BP, body et al. to explain the benefits of yoga practices in diverse and mass index, and blood glucose with a clinically significant frequently comorbid medical conditions hypothesized that improvement in lipid profile.[12] A reduction in all lipid profile stress produces an increased allostatic load and develops a parameters except high‑density lipoproteins was reported disparity of the autonomic nervous system with increased in a yoga‑based lifestyle intervention study which started sympathetic and decreased parasympathetic activity. Yoga- from 4 weeks and lasted for 14 weeks.[13] A study on Surya based practices correct this under activity through the Namaskar revealed improved cardio-respiratory fitness in the stimulation of the vagus nerves and reduce the allostatic load. participants.[14] Another literature review on varying periods of yoga training on young subjects reported significant The human emotions of stress, anger, happiness, pleasure, improvements in overall cardiovascular endurance, increased joy, and sorrow are difficult to measure, but they provide physical and better cardiopulmonary endurance.[15] All these a solid scientific foundation of mind-body relationship results indicate that a yogic lifestyle interference may have

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S239 Rai and Rai: Yoga: the restraint for non-communicable diseases an effect on some adaptable risk factors, which could make Researches have suggested that efficient BP management is clear the protective and therapeutic valuable impact of yoga multifactorial and includes expanding patient and healthcare in CVD. Overall, lifestyle intervention can transform the provider awareness, appropriate lifestyle and food habit evolution of the CVD. modifications, access to care, appropriate treatment, a high level of medication adherence,[21] adequate follow-up and observation. YOGA IN DM Various yogic techniques have been found to be very effective The pathogenesis of DM and its aftermaths has been in the management and control of BP and its aftermaths. linked to chronic stress, anxiety, depression, and also to It is difficult to elucidate the mechanism underlying the an abnormal increase in sympathetic tone and reduction in BP‑lowering effect. Controlled breathing with prolonged parasympathetic activity. Despite the best glycemic controls, breath cycles as practiced in Pranayam may positively alter a number of complications are seen to develop in the the chemoreceptor sensitivity thereby reducing arterial patients leading to considerable disability and discomfort. baroreceptor lassitude and sympathetic outflow.[22] Other Lifestyle modification has been observed as a component potential mechanisms postulate that amplification of tidal in the management of diabetes. The practice of yoga is volume activates the Hering–Breuer reflex mediated by directly associated to improve insulin sensitivity to glucose pulmonary stretch receptors which reduces the chemoreflex signals in Type 2 DM and attenuate the negative relationship sensitivity and upregulates the baroreflex receptor sensitivity between factors causing insulin resistance such as obesity, and thereby decreases arterial BP. It has also been suggested increased waist circumference, and dyslipidemia.[16] Studies that pranayama practices entrain central nervous system and reviews on effect of yoga intervention in Type 2 DM nuclei (in which respiratory and cardiovascular system have clearly disclosed the positive effects of yoga on centers cross)[15] thus positively altering the sympathetic glycemic control, BP, lipid profile, stress, anxiety, and outlay to the blood vessels. depression, but have not recognized the mechanisms of the action of yoga. Manjunatha et al. and Sahay have reported A decrease in systemic vascular resistance and better total that there is diminution in the brisk release of insulin when arterial compliance has also been suggested as some other glucose level tends to fall whereas the insulin release is probable mechanisms of action.[23] However, the overall increased when there is a rise of glucose in blood. Yoga biological mechanism and the integrated neural pathways augments the secretion of insulin as per bodily requirement involved in lowering BP by slow deep breathing have yet to through its neuroendocrinal effects and thereby brings about be completely elucidated. normalcy in the insulin/glucose ratio, which is evocative of better peripheral utilization of insulin and reduced insulin resistance.[17] A few RCTs suggest that yoga and meditation YOGA IN CANCER practices act on the hypothalamic–pituitary–adrenal axis[18] to reduce the sympathetic nervous system tone, decrease cortisol A comprising meta-analysis on the effect of yoga in cancer levels in plasma and elevate brain gamma-Aminobutyric as compared to waitlist or supportive therapy class reveals acid (GABA) levels. The psychoneuroendocrine and improvements in psychological health along with the overall immune mechanisms of the action of yoga in Type 2 DM quality of life.[24] A study on systematic review and meta- epitomize a conceivable line to accept its holistic effects analysis on the physical and psychosocial betterment of yoga on disease modulation. It is very difficult to recognize any in cancer patients and survivors by Buffart and colleagues sole physiological mechanism of action of yoga in Type 2 find out that yoga may be an advantageous intervention DM as the risk factors and etiologies of Type 2 DM are as valuable effects on several physical and psychosocial multifactorial. Yoga produces multi‑systemic effect through symptoms were reported.[25] They presented that strong multitude mechanisms of action. beneficial effects are observed by the practice of yoga on distress, anxiety, and depression, while moderate effects are perceived on fatigue, general health-related quality of life, YOGA IN HYPERTENSION emotional, and social function. They also observed the little beneficial effects on functional well-being. They suggested Hypertension is a disease affecting a large portion of the that yoga practices can be an advantageous form of exercise adult population worldwide. It is a major modifiable risk for cancer patients and survivors. factor for other cardiac diseases and stroke. The origin of hypertension has been suggested to a number of factors as Various complex pathways were suggested by Smith and stress, imbalance in autonomic performance,[19] overactivity Pukallto.[26] They explain the positive outcomes of yoga of the sympathetic nervous system which ultimately practices which enmesh relaxation, acceptance, self- desensitizes cardiopulmonary and arterial baroreceptor reflex efficiency, and coping strategies. Increase in number of and chemoreceptor reflex, leading to a resetting of threshold natural killer cells was reported by Kochupillai et al.[27] in BP values at which regulatory signals are triggered.[20] cancer patients who were practicing Sudarshan Kriya and

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Pranayam (breathing techniques) of yoga after complete in REFERENCES their standard therapy. 1. Available from: http://www.searo.who.int/entity/ noncommunicable_diseases/en/. [Last accessed on 2018 THE FUTURE PROSPECTS May 31]. 2. Available from: http://www.searo.who.int/mediacentre/ Stress has been well accepted as the major culprit for the non- features/2015/international-day-of-yoga/en/. [Last communicable diseases as it weakens the immune system accessed on 2018 May 21]. (neuroimmune axis and psychoneuroimmunology), disturbs 3. Pandey AK, Das A, Vijay VJ, Mohan V. Implication of the hypothalamic–pituitary–axis (neuroimmunoendocrine yoga in non-communicable diseases. J Soc Health and axis) and up-regulate the sympathetic tone of the body. Diabetes 2017;5:88-93. Scientific research in several recent scientific studies has 4. Madanmohan, Udupa K, Bhavanani AB, Shatapathy CC, shown that the physical, physiological, psychological, and Sahai A. Modulation of cardiovascular response to biochemical consequences of yoga are of anti‑stress in exercise by yoga training. Indian J Physiol Pharmacol nature. Mechanisms hypothesized and postulated are the 2004;48:461-5. re‑establishment of autonomic function balance as well as 5. Madanmohan, Thombre DP, Balakumar B, a progress in healing, regenerative, and curative capacity of Nambinarayanan TK, Thakur S, Krishnamurthy N, et al. the individuals which enables us to move from a state of ill Effect of yoga training on reaction time, respiratory health and sickness to the one of fitness and well‑being. endurance and muscle strength. Indian J Physiol Pharmacol 1992;36:229-33. The need of the current time is to have an integrated approach 6. Glaser R, KiecoltGlaser JK. Stressassociated immune toward complete therapy and to utilize yoga therapy in modulation: Relevance to viral infections and chronic harmonization, cooperation, and collaboration with other fatigue syndrome. Am J Med 1998;105:35S42S. systems of medicine such as modern medicine, Ayurveda, and 7. Look Ahead Research Group, PiSunyer X, Blackburn G, naturopathy. Advice on diet and lifestyle is very important, Brancati FL, Bray GA, Bright R, et al. Reduction irrespective of the mode of therapy that is employed for a in weight and cardiovascular disease risk factors in particular patient. individuals with Type 2 diabetes: Oneyear results of the look ahead trial. Diabetes Care 2007;30:137483. 8. Popko K, Gorska E, StelmaszczykEmmel A, CONCLUSION Plywaczewski R, Stoklosa A, Gorecka D, et al. Proinflammatory cytokines Il6 and TNFa and the Yoga has prodigious potential in the control, preventing, and development of inflammation in obese subjects. Eur J managing lifestyle disorders and diseases. The integration of Med Res 2010;15 Suppl 2:1202. active yogic lifestyle can make a distinguishable contribution 9. Aucott L, Rothnie H, McIntyre L, Thapa M, Waweru C, to the enhancement of general health globally. Yoga has Gray D. Longterm weight loss from lifestyle intervention the strength to shunt the progression of non-communicable benefits blood pressure? A systematic review. disease and if initiated early, may also exhibit significant Hypertension 2009;54:75662. cure to the disease and its sequel. The majority of studies 10. LarsonMeyer DE, Heilbronn LK, Redman LM, on yoga and cardiovascular health show positive trends and Newcomer BR, Frisard MI, Anton S, et al. Effect of this augurs well for the future of healthcare in general and calorie restriction with or without exercise on insulin the use of yoga as part of integrative health-care system sensitivity, betacell function, fat cell size, and ectopic lipid in particular. The major benefit of yoga may occur due to in overweight subjects. Diabetes Care 2006;29:133744. the psychosomatic harmonizing effect and restoration of 11. Anderson JW, Liu C, Kryscio RJ. Blood pressure physical, mental, emotional, and spiritual balance which response to transcendental meditation: A metaanalysis. has been proven in numerous scientific short- and long-term Am J Hypertens 2008;21:3106. studies. 12. Vyas R, Dikshit N. Effect of meditation on respiratory system, cardiovascular system and lipid profile. Indian J With no considerable side effects and several collateral Physiol Pharmacol 2002;46:48791. benefits yoga can be practiced by all, even ill, elderly, 13. Sarvottam K, Yadav RK, Mehta N, Mahapatra SC. Effect or disabled individuals and should be recommended as a of short term yoga on resting energy expenditure and beneficial adjuvant for patients of various non-communicable lipid profile in overweight/obese subjects: A preliminary disorders as it is a safe, simple, and economical therapy. study. Indian J Physiol Pharmacol 2010;54:133. Yoga can be practiced anywhere by people of all age groups, 14. Ornish D, Scherwitz LW, Billings JH, Brown SE, irrespective of their socio-economic status, it fits in very well Gould KL, Merritt TA, et al. Intensive lifestyle changes for with the healthy lifestyle, due to all these unique qualities of reversal of coronary heart disease. JAMA 1998;280:20017. yoga, the WHO has been strongly advocating throughout the 15. Selvamurthy W, Sridharan K, Ray US, Tiwary RS, life cycle - from childhood to healthy aging.[2] Hegde KS, Radhakrishan U, et al. A new physiological

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S241 Rai and Rai: Yoga: the restraint for non-communicable diseases

approach to control essential hypertension. Indian J and cardiovascular risk. Am J Hypertens 2000;13:112S22S. Physiol Pharmacol 1998;42:20513. 23. Oneda B, Ortega KC, Gusmão JL, Araújo TG, Mion D Jr. 16. Mody BS.Acute effects of Surya Namaskar on the Sympathetic nerve activity is decreased during device- cardiovascular and metabolic system. J Bodyw Mov guided slow breathing. Hypertens Res 2010;33:708-12. Ther 2011;15:3437. 24. Tsauo JY, Lin KY, Hu YT, Chang KJ, Lin HF. Effects 17. Sengupta P. Health impacts of Yoga and pranayama: of Yoga on psychological health, quality of life, A stateoftheart review. Int J Prev Med 2012;3:44458. and physical health of patients with cancer: A meta- 18. Innes C. Interconnected pathways of yoga to reduce the analysis. Evidence-Based Complementary Altern Med risk of cardiovascular diseases. J Am Board FamPract 2011;2011:659876. 2005;s18:491519. 25. Buffart LM, van Uffelen JG, Riphagen I, Brug J, 19. Altena MR, Kleefstra N, Logtenberg SJ, Groenier KH, van Mechelen W, Brown WJ, et al. Physical and Houweling ST, Bilo HJ. Effect of deviceguided psychosocial benefits of Yoga in cancer patients and breathing exercises on blood pressure in patients with survivors, a systematic review and metaanalysis of hypertension: A randomized controlled trial. Blood Press randomized controlled trials. BMC Cancer 2012;12:559. 2009;18:2739. 26. Smith KB, Pukall CF. An evidence-based review of 20. Pagani M, Somers V, Furlan R, Dell’Orto S, Conway J, Yoga as a complementary intervention for patients with Baselli G, et al. Changes in autonomic regulation induced cancer. Psycho Oncol 2009;18:465. by physical training in mild hypertension. Hypertension 27. Kochupillai V, Kumar P, Singh D, Aggarwal D, 1988;12:60010. Bhardwaj N, Bhutani M, et al. Effect of rhythmic 21. Chobanian AV, Bakris GL, Black HR, Cushman WC, breathing (Sudarshan kriya and pranayam) on immune Green LA, Izzo JL Jr., et al. Seventh report of the joint functions and tobacco addiction. Ann N Y Acad Sci national committee on prevention, detection, evaluation, 2005;1056:242-52. and treatment of high blood pressure. Hypertension 2003;42:1206-52. 22. Brook RD, Julius S. Autonomic imbalance, hypertension, Source of Support: Nil. Conflict of Interest: None declared.

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S242 Phytochemistry and pharmacology of Swertia corymbosa

Vineet Sharma, DevNath Singh Gautam Department of Rasa Shastra, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India

ABSTRACT

Swertia corymbosa belonging to family Gentianaceae is a stout erect herb, found Western Ghats from Maharashtra to South Kanara at 1200 m. Its medicinal usage is well documented in Indian traditional medicine such as the Ayurveda, Unani, Siddha, and other conventional medical systems. In India, local healers have practiced this plant

REVIEW ARTICLE REVIEW as a substitute of Swertia chirayita for the management of fever, diarrhea, jaundice, hyperglycemia, inflammation, and neurological diseases. The phytochemical study had led to the isolation of flavonoids, triterpenes, alkaloids, glycosides, etc. Pharmacological activities (in vitro and in vivo) of various parts of the plant summarized include anxiolytic, sedative, anticonvulsant, antioxidant, analgesic, anti-inflammatory, antipyretic, antimicrobial, antidiabetic, antihyperlipidemic, and antiproliferative activity. S. corymbosa developed as a great source of folkloric medicine for the treatment of pain, diabetes, infectious diseases, neurological, and inflammatory disorders. Further, research is required in the field of pharmacokinetics, efficacy, toxicology, and clinical importance of the plant as well as its bioactive chemical constituents.

Keywords: Anticonvulsant, antiproliferative, pharmacokinetics, Swertia corymbosa

INTRODUCTION ETHNOPHARMACOLOGY

wertia corymbosa (Gentianaceae), is Roots of the S. corymbosa are used for the treatment of venereal stout erect herbs, located Western Ghats diseases, skin diseases, sores, injuries, and ulcer. The roots of from Maharashtra to South Kanara at S. corymbosa are used for the treatment of soreness and pains S [1] 1200 m. Plants are distinguished by solid in the lower limbs. The whole plant of S. corymbosa has been erect herbs; 30–40 cm high; stem four-angled, applied for the cure of diarrhea, fever, jaundice, and diabetic. extensively branched. Leaves of the plant Particularly in the area of Tirunelveli district and Vellingiri are identified by 2–3 cm ovate, acute, and hills of Coimbatore, tribal’s S. corymbosa was usually used subamplexicaul at the base with three-ribbed. to control diabetes and nervous diseases.[3] S. corymbosa The cymes are terminal along with corymbose. recommended that aerial parts are used as the main ingredient The flowers are tightly arranged with 1 cm for the manufacture of Ayurvedic herbal medicines against long bracts, lanceolate pedicel 13 mm long, diabetics.[4] In the Unani system, S. corymbosa is used as an lanceolate free calyx lobes 11 mm Χ 1.5 mm, astringent tonic, stomachic, reduces inflammation, a sedative white corolla 12 mm Χ 4 mm with bluish to the pregnant uterus, and chronic fevers.[5] S. corymbosa spots, lobes 4, connate at base only; nectary leaves traditionally used in Indian medicine as an antidote chamber at the base of corolla, covered with for poisoning, diarrhea, and as stomach wash in cattle.[6] Due an orbicular lid, rim of the chamber with to bitterness quality, this plantis used as substitute of Swertia scabrous bristle; stamens 4, all fertile; ovoid chirayita.[1] ovary with short style; and stigma capitate. Capsules oblong, 5–6 mm long, dehiscing by two valves; seeds many, reticulate. Beneath Address for correspondence: leaves are more packed than top leaves and Dr. DevNath Singh Gautam, Department of Rasa Shastra, usually falling short. Stems are with four Faculty of Ayurveda, Institute of Medical Sciences, different angles. Petals are a single dot-like Banaras Hindu University, Varanasi - 221 005, honey gland at the base which is incorporated Uttar Pradesh, India. Phone: +91-9450824065. with a minute fimbriate rough appendix and E-mail: [email protected] uncommon nature.[2]

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S243 Sharma and Gautam: A Review on Swertia corymbosa

PHYTOCHEMISTRY

Phytochemical investigation on aerial parts of S. corymbosa led to the isolation of decussating (1), gentiacaulein (2), swertianin (3), methylswertianin (4), 8-hydroxy- 1,2,4,6-tetramethoxyxanthone (5), 1,2-dihydroxy-6- methoxyxanthone-8-O-β-D-xylopyranosyl (6),[7] loganic acid (7), swertiamarin (8), sweroside (9), gentiopicroside (10), isovitexin (11), amoroswertin (12), amarogentin (13), from its aerial parts[8] 1, 2, 8-trihydroxy-6-methoxy xanthone (14),[9] 3-allyl-2, 8dihydroxy-1, 6-dimethoxy-9H-xanthen-9-one (15), norswertianin (16), 1,3,6,8-tetrahydroxyxanthone (17), 1,3 dihydroxyxanthone (18), allyloxy xanthone (19), isolated from chloroform fraction of aerial parts of S. corymbosa[10] friedelin (20), epi-friedelinol (21), mangiferin (22), α-amyrin (23), lupeol (24), oleanolic acid (25), ursolic acid (26),[11] and 1, 5, 8-trihydroxy-3-methoxyxanthone (27) was isolated from whole plant of methanol extract of S. corymbosa.[12] R1 R2 R3 R4 R5 15 MeO OH Allyl MeO OH 16 OH OH H OH OH 17 OH H OH OH OH 18 OH H OH H H 19 MeO Allyl‑O H MeO OH

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S244 Sharma and Gautam: A Review on Swertia corymbosa

PHARMACOLOGICAL ACTIVITY ANTIPROLIFERATIVE ACTIVITY

Antioxidant Activity In vitro antiproliferative study was performed in the human cervical cancer cell line, hepatocellular carcinoma, In vitro, the antioxidant activity of isolated compound from neuroblastoma, and NIH 3T3 mouse embryonic fibroblasts the aerial part of S. corymbosa was performed. Compound cell lines using MTT assay. The isolated compounds 3 and 6 found that strong scavenging effects on 2,2-diphenyl- 6 were found that a significant antiproliferative activity with 1-picrylhydrazyl (DPPH), ABTS, superoxide anion, IC50 was 7.3, 12.46, and 34.67 mol/mL and 13.35, 25.56, nitric oxide, hydroxyl radical scavenging activities, ferric and 41.56 mol/mL correspondingly. While IC50 values of reducing antioxidant power, metal chelating, and lipid standard drug (camptothecin) was found to be 6.56, 5.76, peroxidation with IC50 were found to be 07.19 ± 4.56 mol/ 10.43 and 6.24 mol/mL against Neuroblastoma, HeLa, NIH mL, 42.62 ± 0.25 mmol/L TE/g, 57.89 ± 3.45 mol/mL, 3T3 and HepG2 respectively.[7] The methanol extract has 18.45 ± 1.23 mol/mL, 12.13 ± 2.76 mol/mL, 14.76 ± 0.10 effectively reduced the proliferation of HepG2 and HeLa molar Fe (II)/g, 213.85 ± 27.18 EDTA mg/g, and 19.21 ± cell lines with the IC50 values of 61.64 and 87.90 μg/mL in a 3.45 mol/mL, respectively.[7] dose-dependent mode.[14] While the isolated compound (15) from S. corymbosa was found significantly cytotoxic against The antioxidant activity of methanol extract of aerial human cancer cell lines HCT116, HeLa, and AGS, and feebly parts and root of S. corymbosa was evaluated in alloxan- active against normal NIH 3T3 cell line.[10] induced diabetic rats. The diabetic rats were administered with methanol extract of S. corymbosa at a dose of 150 mg/kg, i.p. body weight for 14 days. The antioxidant ANTI-INFLAMMATORY ACTIVITY activity of the methanol extract of S. corymbosa was analyzed by estimating the levels of catalase, glutathione In vitro anti-inflammatory activity was evaluated against peroxidase, and superoxide dismutase with the normal and denaturation of egg albumin and membrane stabilization. diabetic-treated albino rats. A highly significant reduction The diclofenac sodium (standard drug) showed significant in the activity of scavenging mitochondria enzymes is activity as compared with isolated compound 6. The IC observed in alloxan-induced rats. The methanol extract 50 of the isolated compound against protein denaturation and of S. corymbosa has enhanced mitochondrial enzymatic membrane stabilization was found to be 18.75 µM/mL and antioxidant activity and suppressed lipid peroxidation and 12.57 µM/mL, respectively.[7] the reduction in the activities of SOD, CAT, and GPX in alloxan-induced rats.[13] The anti-inflammatory activity of the isolated compound 3 and 6 showed maximum inhibition (60.28% and 71.80%) on In vitro, the antioxidant activity of mega extract (petroleum carrageenan-induced rat paw edema at a dose of 50 mg/kg, ether, chloroform, ethyl acetate, methanol, and hot water) of body weight after 5 h of drug administration, while standard aerial parts of S. corymbosa was performed. The methanol [17] extract of aerial part was showed active scavenging effects drug (indomethacin) produced 64.44% of inhibition. on DPPH free radicals, radical cation scavenging, ferric reducing, superoxide radicals, metal chelating, hydroxyl At the dose level of 100 and 200 mg/kg, methanol extract radical scavenging, and nitric oxide with IC , 23.54 μg/mL, of aerial parts of S. corymbosa showed maximum inhibition 50 [18] 32711.05 ± 339.94 μmol TAA/g extract, 1955.29 ± 35.14 (40.85% and 63.75%) after 5 h of drug administration. mmol Fe (II)/mg extract, 75.74% at a level of 100 μg, 79.81 ± 5.13 mg EDTA/g extract, 52.42%, and 70.15%, respectively.[14] ANTIDIABETIC ACTIVITY

The antioxidant activities of methanol extracts from non- Antidiabetic activity of isolated compounds 6 and 14 was embryonic callus, globular stage of somatic embryos, evaluated in streptozotocin-nicotinamide-administered heart-shaped stage of somatic embryos, and cotyledonary diabetic rats. At the dose level of 25 and 50 mg/kg, diabetic embryos of S. corymbosa were evaluated in vitro assays, rats were administered isolated compound and standard drug i.e., DPPH, ABTS, and ferric reducing antioxidant. (glibenclamide, 10 mg/kg, i.p.) for 28 days. In this activity, The methanol extract of S. corymbosa was found good retro-orbital puncture method is used for the collection of antioxidant activity.[15] blood sample. The blood samples were tested for fasting blood glucose levels with glucose oxidase-peroxidase reactive strips The whole plant of aqueous extract of S. corymbosa showed and glucometer. In the oral glucose tolerance tests (OGTT), scavenging results on DPPH free radicals and ferric reducing at the level of dose 2 mg/kg, glucose was administered to antioxidant power with 33.82% RSA and 1.07 mg AEAC/g, non-diabetic control rats treated with standard drug and respectively.[16] isolated compound. After 3 h of the treatment, isolated

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S245 Sharma and Gautam: A Review on Swertia corymbosa compounds (50 mg/kg b.w.) showed the utmost reduction of ANTIHYPERLIPIDEMIC ACTIVITY 83% in the level of blood glucose of diabetic rats. At the dose level of 50 mg/kg, oral administration of both compounds The isolated compounds 6 and 14 were performed in showed significant decrease in blood glucose, glycosylated streptozotocin-induced diabetic rats for antihyperlipidemic hemoglobin, serum glutamic oxaloacetic transaminase, serum activity. At the dose level of 60 mg/kg, diabetes was glutamic pyruvic transaminase, serum alkaline phosphatase, induced by intraperitoneal injection of streptozotocin. The serum urea, and creatinine with a significant increase in isolated compound at the dose level of 50 mg/kg exhibited plasma insulin level in streptozotocin-induced diabetic rats. a significant reduction in serum triglycerides, cholesterol, For OGTT, the compound showed a significant decrease in and low-density lipoprotein, in diabetic-treated rats when blood glucose levels at 120 and 180 min.[9] compared to control rats which indicated the protective role against liver and kidney damage. The histopathological In vitro antidiabetic activity of the methanol extracts examination showed protected tissues of liver, kidney, of aerial parts of S. corymbosa was investigated using and pancreas, against peroxidation damage and reported α-amylase and α-glucosidase enzyme inhibitory activity. At tissue probity. No significant results were obtained in the the oral dose level of 125, 250, and 500 mg/kg, extract was normoglycemic rats.[9] given in streptozotocin-induced diabetic rats for 28 days. Hypoglycemic outcomes, OGTT, body weight, lipid profile, biochemical, and histopathological analysis were MOLECULAR DOCKING STUDY evaluated. The methanol extract was found good inhibitor of α-glucosidase and α-amylase. The methanol extract The molecular interaction of compound 6 and 14 significantly reduced in the concentrations level of blood and glibenclamide was investigated with numerous glucose, total cholesterol, low-density lipoprotein cholesterol, diabetes mellitus-associated protein targets (fructose-1, malondialdehyde, serum triglycerides and the vital increase 6-bisphosphatase 1, glucokinase, and 11-β-hydroxysteroid in the concentrations of high-density lipoprotein cholesterol, dehydrogenase). The reduced protein sulfonylurea receptor and serum insulin, along with body weight. Histopathological 1 revealed that both ligands hold binding affinity with whole study revealed the regeneration of β-cells in the pancreas that protein targets but for 11-β-hydroxysteroid dehydrogenase was beginning necrosed by streptozotocin. In the OGTT, target protein for which ligand 1 was found no interaction [8] the extract enhanced the glucose tolerance. The aqueous and the ligand provided the binding formation. Consequently, extract of S. corymbosa showed less antihyperglycemic and both compounds can be recognized for developing into a [16] antiglycation activity against OGTT. potent antihyperglycemic drug.[9]

Analgesic Activity ANTIMICROBIAL ACTIVITY Analgesic effects of compounds 3 and 6 were performed in The isolated compound 6 was evaluated against albino mice by hot plate and acetic acid-induced writhing Staphylococcus aureus and Streptococcus pneumoniae methods. The hot plate reaction time for both compounds (pathogenic Gram-positive bacteria) and Escherichia coli, was found to be 9.88 and 11.78 s which showed significant Pseudomonas aeruginosa, Klebsiella pneumoniae, and exhibition. The Compound 3 and 6 showed diminish writhing Bacillus subtilis (Gram-negative bacteria) by the paper disc sign (70.60, 76.85%) in acetic acid induced test respectively. method and minimum inhibitory concentration. At 25 µg/ [17] Methanol extract (200 mg/kg, for 240 min) showed better mL concentration, isolated compound showed antibacterial analgesic activity compared with standard drug pentazocine activity toward S. pneumoniae and E. coli with MIC value for hot plate reaction time. Pretreatment with methanol of 3.90 µg/mL, and inhibition zone was found to be 21.21 ± extract of S. corymbosa (100 and 200 mg/kg, body weight) 0.25 and 20.27 ± 0.11 mm, respectively. However, compound reduced pain 55.64% and 75.01%, respectively, while was found inadequate activity against the other examined 71.91% inhibition was found for indomethacin (standard bacteria.[7] drug, 25 mg/kg, body weight).[18]

The aqueous, methanol, chloroform, and hexane extracts Anxiolytic Activity of the whole plant of S. corymbosa were tested for in vitro antimicrobial activity against Salmonella aureus, Salmonella Anxiolytic activity of methanol extract of the aerial parts typhi, Aeromonas hydrophila, B. subtilis, Chromobacterium of S. corymbosa was studied in albino mice using the violaceum, P. aeruginosa, and Vibrio cholera. The aqueous elevated plus maze, open field test models. Administration extract of S. corymbosa showed maximum inhibitory activity of methanol extract of S. corymbosa (125–500 mg/kg) to the against S. aureus. The methanol and chloroform extract of S. rats showed the significant improvement in the incidence of corymbosa inhibited S. typhi. The modest inhibitory activity the open arm and minimum number of entries in the closed was found against V. cholera, P. aeruginosa, A. hydrophila, arm. The methanol extract and diazepam showed noteworthy C. violaceum, S. aureus, and B. subtilis.[11] improvements in the entries of total number into the two

International Journal of Green Pharmacy • Vol 11 • Special Issue 2018 | S246 Sharma and Gautam: A Review on Swertia corymbosa arms. In open field test, methanol extract of S. corymbosa of S. corymbosa provides a logical support for its various causes the significantly reduced number of central motor and folkloric uses. Phytochemistry investigations carried out on ambulation in the mice.[19] S. corymbosa had pointed to the isolation of some groups of plant metabolites. Anticonvulsant Activity

The methanol extract of the aerial parts of S. REFERENCES corymbosa was evaluated for anticonvulsant potential by pentylenetetrazole, maximal electroshock (MES), 1. Khare CP. Indian medicinal plants. Vol. 3. Verlag, Berlin: and isoniazid-induced convulsions models. In Springer; 2007. p. 633. pentylenetetrazole model, at a dose of 125, 250, and 500 2. Nampy S, Shahina PM, Haseena T, Ashwini HS. mg/kg of methanol extract of S. corymbosa protected A taxonomic revision of Swertia L. (Gentianaceae) 33.33%, 50.0%, and 100%, respectively, of the animals in South India, with one new species and seven against seizures. The convulsion and latency period were lectotypifications. Phytotaxa 2015;195:31-52. found to be 89.20 ± 4.24 s in control group. The methanol 3. Abraham Z. Ethnobotany of the todas, the kotas, the extract significantly prolonged the span of ionized induced irulas of the Nilgiris. In: Jain SK. editor. Glimpses of seizures at each three-dose levels and showed a dose- Indian Ethnobotany. New Delhi: Oxford and IBH; 1981. dependent improvement in the anticonvulsant activity. p. 26-30. The methanol extract revealed a dose-dependent increase 4. Oudhia P. Indigenous Medicinal Rice P5-C120A in hindrance of the origin time of seizures caused by MES- (Allelopathically Enriched) compatibility in Swertia induced convulsion moreover reduced the duration of corymbosa (Griseb.) Wight ex Clarke var. Corymbosa tonic hindlimb extension.[19] based Herbal Formulations. Pankaj Oudhias Expert Comments on Medicinal Rice of Asia. Audio Bank on Sedative Activity Biodiversity and Traditional Healing; 2012. 5. Kirtikar KR, Basu BD. Indian Medicinal Plants. Leader The sedative activity of methanol extract of the aerial parts Road, Allahabad, India: Latit Mohan Basu; 1984. of S. corymbosa was performed in albino mice using the p. 1664-5. spontaneous motor and rotarod performance model. The 6. Iqbal Z, Lateef M, Khan MN, Jabbar A, Akhtar MS. protective effect of methanol extract of S. corymbosa (500 Anthelmintic activity of Swertia chirata against mg/kg, b.w.) standard drug diazepam (2 mg/kg, b.w.) on gastrointestinal nematodes of Sheep. Fitoterapia locomotor activity in rats was found to be 55.38% and 2006;77:463-65. 49.59%, respectively, after 1 h of drug administration. 7. Mahendran G, Manoj M, Prasad KJ, Bai VN. At the dose level of 500 mg/kg, methanol extract Antioxidants, anti-proliferative, anti-inflammatory, administered rats maintained on the rotating rod for more anti-diabetic and anti-microbial effects of isolated than 276.35 ± 7.58 s.[19] compounds from Swertia corymbosa (Grieb.)Wight ex C.B. Clark-An in vitro approach. Food Sci Human Well Antipyretic Activity 2015;4:169-79. 8. Mahendran G, Thamotharan G, Sengottuvelu S, Bai The antipyretic activity of methanol extract of the aerial VN. RETRACTED: Anti-diabetic activity of Swertia parts of S. corymbosa was examined on yeast-induced corymbosa (Griseb.) wight ex C.B. Clarke aerial pyrexia in albino rats. Yeast suspension (10 mg/kg) enhanced parts extract in streptozotocin induced diabetic rats. rectal temperature 24 h following subcutaneous injection. J Ethnopharmacol 2014;151:1175-83. Methanol extract (100 and 200 mg/kg) exhibited the 9. Mahendran G, Manoj M, Murugesh E, Sathish Kumar R, significant reduction in yeast-induced raised temperature in Shanmughavel P, Rajendra Prasad KJ, et al. In vivo anti- a dose-dependent manner. The effect extended up to 5 h after diabetic, antioxidant and molecular docking studies of 1, 2, the drug treatment. The antipyretic effect of methanol extract 8-trihydroxy-6-methoxy xanthone and 1, 2-dihydroxy-6- was got significant to paracetamol (standard drug, 150 mg/ methoxyxanthone-8-O-β-D-xylopyranosyl isolated from kg, p.o.).[18] Swertia corymbosa. Phytomedicine 2014;21:1237-48. 10. Uvarani C, Arumugasamy K, Chandraprakash K, Sankaran M, Ata A, Mohan PS, et al. A new DNA- CONCLUSION intercalative cytotoxic allylic xanthone from Swertia corymbosa. Chem Biodivers 2015;12:358-70. The comprehensive literature review showed S. corymbosa 11. Ramesh N, Viswanathan MB, Saraswathy A, to be valuable remedial plant used for the ethnomedical Balakrishna K, Brindha P, Lakshmanaperumalsamy P, treatment of pain, diarrhea, ulcer, diabetes, jaundice, fever, et al. Antimicrobial and phytochemical studies of etc., in India. Pharmacological investigations carried out on Swertia corymbosa. Fitoterapia 2002;73:160-4. the aerial parts of plant extract and the isolated compound 12. Saraswathy A, Ariyanathan S. 1, 5, 8-Trihydroxy

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