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Asian Pac J Trop Biomed 2014; 4(3): 245-252 245

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Document heading doi:10.1016/S2221-1691(14)60240-9 2014 by the Asian Pacific Journal of Tropical Biomedicine. All rights reserved. 襃 An update on Ayurvedic herb Convolvulus pluricaulis Choisy

Parul Agarwa*, Bhawna Sharma, Amreen Fatima, Sanjay Kumar Jain Institute of Pharmacy, Bundelkhand University, Jhansi 284121, U.P, India

PEER REVIEW ABSTRACT

Peer reviewer Convolvulus pluricaulis C. pluricaulis Choisy ( ) is a perennial herb that seems like morning glory. Prof. Vanessa Steenkamp, Department All parts of the herb are known to possess therapeutic benefits. The is used locally in 2034 of Pharmacology, P.O. Box , Indian and Chinese medicine to cure various diseases. It is usedetc in Ayurvedic formulation for Pretoria 0001, South Africa. E-mail: chronic cough, sleeplessness, epilepsy, hallucinations, anxiety . Based on the comprehensive [email protected] review C.of plantpluricaulis profile, pharmacognosy, phytochemistry, pharmacological and toxicological data on the C. pluricaulis, there will be more opportunitiesC. pluricaulis for the future research and development Shashi Alok, Assistant Professor, on the herb . Information on the was collected via electronic search Institute of Pharmacy, Bundelkhand (using Pub Med, SciFinder, Google Scholar and Web of Science) and library search for articles University, Jhansi (U.P.), India. published in peer-reviewed journals. Furthermore, information also was obtained from some +91 9450036362 Tel: local books on ethnopharmacology.C. pluricaulisThis paper covers the literature, primarily pharmacological, E-mail: [email protected] from 1985 to the end of 2012. The is an important indigenous medicine, which has a long medicinal application for liver disease, epileptic disease, microbial disease, cytotoxic and Comments viral diseases, central nervous system (CNS) disease in Ayurvedic medicine, traditional Chinese medicine and other indigenousin vitro medicalin vivo systems. The isolated metabolites and crude extract This paper is a good review paper have exhibited a wide of and pharmacological effect, including CNS depression, on AyurvedicC. and pluricaulis pharmacological anxiolytic, tranquillizing, antidepressant, antistress, neurodegenerative, antiamnesic, antioxidant, activities of . Citations hypolipidemic, immunomodulatory, analgesic, antifungal, antibacterial, antidiabetic, antiulcer, used are also a good resources for anticatatonic, and cardiovascular activity. A chemical study of this plant was then initiated, reviewing and very informative to which led to the isolation of carbohydrats, proteins, alkaloids, fatty acids, steroids, coumarins, all the Ayurvedic and traditional flavanoids, and glycosides as active chemicals that bring about its biological effects. A series of practitioners. pharmacognostical studies of this plant show that it is a herb, its stemC. and pluricaulis leaves are hairy, more Details on Page 251 over it has two types of stomata, anisocytic and paracytic. A herb, has emerged as a good source of the traditional medicine for the treatment of liver disease, epileptic disease, microbial disease, cytotoxic and viral diseases, and CNS disease. Pharmacological results have validated the use of this species in traditional medicine. All the parts of the herb are known to possess therapeutic benefits. Expansion of researchC. pluricaulismaterials would provide more opportunities for the discovery of new bioactive principles from .

KEYWORDS Convolvulus pluricaulis Choisy, Pharmacognosy, Microscopy, Macroscopy, Phytochemistry, Pharmacology

1. Introduction humans recognized their dependence on nature for a healthy life, and since that time humanity has depended on the In the last few years, there has been an exponential growth diversity of plant resources for food, clothing, shelter, and

in the field of herbal medicine, and these drugs are gaining medicine to cure myriads of ailments[2]. Shankhpushpi of popularity both in developing and developed countries the Ayurvedic pharmacopeia of India consists of the whole Convulvulus pluricaulis because of their natural origin and less side effects[1]. Early plant of Choisy ()

*Corresponding author: Parul Agarwal, Institute of Pharmacy, Bundelkhand Article history: University, Jhansi, 284121, U.P, India. Received 15 Nov 2013 Tel: +919415987306 Received in revised form 27 Nov, 2nd revised form 5 Dec, 3rd revised form 12 Dec 2013 E-mail: [email protected] Accepted 16 Jan 2014 Foundation Project: Supported by Institute of Pharmacy, Bundelkhand University, Available online 28 Mar 2014 Jhansi, U.P, India (Grant No. BU/PHARM/2013/1003). Parul Agarwal et al./Asian Pac J Trop Biomed 2014; 4(3): 245-252 246 C. pluricaulis Convulvulus microphyllus 1.2. Scientific classification syn ( ) and Sieb. ex C. microphyllus C. pluricaulis Spreng ( )[3]. other than C. pluricaulis use the name Shankhpushpi in different parts of the country. The scientific classification of is alsinoides Clitoria ternatea These include Linn, demonstrated as follows[8]: Canscora decussata Linn and Schult. Kingdom: Plantae Indian Council of Medical Research has given quality Sub-kingdom: Tracheobionta C. pluricaulis standards for drug in its publication[4]. Super-division: Spermatophyta Although these plants proved their scientific potential in Division: Magnoliophyta central nervous system depression, anxiolytic, tranquillizing, Class: Magnoliopsida antidepressant, antistress, neurodegenerative, antiamnesic, Sub-class: Asteridae antioxidant, hypolipidemic, immunomodulatory, Order: analgesic, antifungal, antibacterial, antidiabetic, antiulcer, Family: Convolvulaceae Convolvulus anticatatonic, and cardiovascular activity. These are Genus: pluricaulis reported to contain several types of alkaloids, flavanoids, Species: and coumarins as active chemicals that bring about its 1.3. Vernacular names biological effects[5]. The plant has been found to be effective in reducing C. pluricaulis different types of stress including psychological, chemical The vernacular names of is described as and traumatic. The ethanolic and methanolic extracts of the follows: Sankhapuspa whole plant reduced spontaneous motor activity, potentiated Sanskrit: Sankhapuspi pentobarbitone hypnosis and morphine analgesia, reduced Bengal: Shankhavali fighting response, abolished the conditioned avoidance Gujarathi: Shankhapushpi, Aparajit response, antagonized convulsive seizures and tremorine Hindi: Bilikanthisoppu induced tremors in mice. The juice of whole plant prevents Kannada: Shankhavela excessive menstruation. The fine paste made by grinding the Marathi: Shankhapuspi plant is helpful to cure abscess. Ethanolic extract of whole Punjabi: Sanghupushpam, kakkurattai plant when administred to cholesterol fed gerbils, reduced Tamil: Shankhapushpi serum cholesterol, Low density lipoprotein cholesterol, Telugu: triglycerides and phospholipids significantly after 90 d. 1.4. Description The root extract of this plant regulated hyperthyroidism in C. pluricaulis female mice. The juice of fresh whole plant of C. pluricaulis possessed anti-ulcerogenic effect and is comparable to is a perennial herb that seems like morning sucralfate. Ethanolic extract of the entire plant exerted a glory. Its branches are spread on the ground and can be negative inotropic action on amphibian and mammalian more than 30 cm long. The flowers are blue in color (5 mm) myocardium. It also exerted spasmolytic activity on smooth and the leaves, which are elliptic in shape (2 mm), are muscles[6]. located at alternate positions with branches or flowers. Aloe Known as weed in English, the herb is commonly found 1.1. Plant profile and synonyms in India, especially in the state of Bihar[9]. , 1.5. Chemical constituents Figure 1 shows the profile of this plant and the synonyms C. pluricaulis C. microphyllus of this plant include and [7]. C. pluricaulis The chemical constituents of are shown in

Table 1[5]. 1.6. Medicinal importance of C. pluricaulis

C. pluricaulis is of various medicinal uses. It is used for treatment of hypertension, neurodegenerative diseases, ulcers, high blood pressure, epilepsy, vomiting, diabetes, sun stroke and bleeding. In addition, it can also be used to improve memory and decrease cholesterol[10].

1.7. Traditional uses

Figure 1. C. pluricalis Many previous studies have reported the traditional uses . Parul Agarwal et al./Asian Pac J Trop Biomed 2014; 4(3): 245-252 247 Table 1 C. pluricaulis Chemical constituents of . Class Chemical constituents Carbohydrats D-glucose, maltose, rhamnose, sucrose, starch and other carbohydrats Proteins and amino acids Proteins and amino acids Alkaloids Shankhapushpine, convolamine, convoline, convolidine, convolvine, confoline, convosine Fatty acids/volatile acids/fixed oil Volatile oils, fatty acids, fatty alcohols, hydrocarbons,myristic acids, palmitic acids and linoleic acids β Phenolic/glycosides/triterpenoids/steroids Scopoletin, -sitosterol, ceryl alcohols, 20-oxodotriacontanol, tetratriacontanoic acids, flavonoid-kampferol, steroids-phytosterols C. pluricaulis. of This plant is reported to be a prominent Table 3 memory improving drug, a psychostimulant and tranquilize, C. Preliminary microscopical characters of ethanolic extracts of T pluricaulis and reduce mental tension. here is a pertinent reference in (leaves). A C. pluricaulis yurvedic literature about the use of the drug as brain tonic Characters in hypotensive syndromes. The pharmacological studies Stem structures Outline in Terete, wings absent of the herb have shown varying degree of its hypotensive transverse section and tranquilizing effects. Clinical studies have exhibited Cuticle Straited C. pluricaulis demonstrable beneficial effects of on the Trichomes covering Present, conical, unicellular patients of anxiety neurosis. The herb induces a feeling Glandular Present, stalk unicellular, head of calm and peace, good sleep and a relief in anxiety, multicellular C P stresses, mental fatigue, producing a significant reduction hlorenchyma resent Collenchyma Present in the level of anxiety, neuroticism arising due to various Endodermis Indistinct T levels of stresses. he herb appears to produce its action Pericyclic fibers Present by modulation of neurochemistry of the brain. The plant Phloem fibers Present improves the balance and vitiation in kapha-vata-pitta Pith Cells pitted in older stem doshas, and the herb is astringent and bitter[11]. Leaf structures Outline in Concave-convex transverse section Collenchyma Present beneath upper 2. Macroscopic characters epidermis Calcium oxalate Plenty, along veins Lamina Isobilateral Preliminary macroscopical characters of ethanolic C. pluricaulis Cuticle Straited ( ) T 2[12] extracts of leaves are given in able . Trichomes Present Table 2 Stomata Both anisocytic and paracytic C. types on either side Preliminary macroscopical characters of ethanolic extracts of pluricaulis S U 202 216 238 (leaves). tomata number pper surface - - C. pluricaulis Lower surface 188-223-251 Characters Stomatal index Upper surface 16.9-18.0-17.2 Stem Length Several prostrate stems (10-30 cm) Lower surface 14.8-16.3-17.2 structures Surface Clothed with silky hairs Vein-islet number 7.5-8.0-9.0 Internodes 10-12 mm Extractive value Water soluble 18.21 Taste Tasteless Alcohol soluble 16.14 Leaf Dimension Length=1.12 cm; breadth=0.1 cm structures Attachment Leaf stalk absent Lamina Thin 4. Pharmacological activities Stipules Exstipulated Leaf lamina shape Linear Preliminary pharmacological activities of ethanolic Leaf margin Entire C. pluricaulis ( ) T 4[14-29] Leaf apex Acute extracts of leaves are given in able . Leaf base Decurrent Leaf texture Whole (brittle) 5. Phytochemistry Venation Parallel Phyllotaxy Alternate Leaf surface Hairy The preliminary phytochemical screening carried out on C. pluricaulis ethanolic extracts of (leaves) revealed the presence of phytoconstituents such as alkaloids, glycosides, flavonoids, carbohydrates, proteins, sterols, gum and 3. Microscopic characters mucilages compounds. Diverse pharmacological properties and structurally novel compounds have been found for C. Preliminary microscopical characters of ethanolic extracts the alkaloids, flavanoids, glycosides, and steroids in C. pluricaulis pluricaulis of (leaves) are given in Table 3[13]. suggesting that these compounds may be the Parul Agarwal et al./Asian Pac J Trop Biomed 2014; 4(3): 245-252 248 Table 4 C. pluricaulis Preliminary pharmacological activities of ethanolic extracts of (leaves). Plant part/ Standard Activity Dose/model Result extract Drug C. pluricaulis Antioxidant Whole part/ 84%, 83%, 48%/DPPH Ascorbic acid The extract possesses significant anticonvulsant activity in vitro. activity chloroform model when tested µ C. pluricaulis Antioxidant Whole part/ 41 g/mL/DPPH model Ascorbic acid The extract demonstrated significant free radical activity methanolic scavenging effect. C. pluricaulis ’ Anticonvulsant Whole part/ 500, 1 000 mg/kg/MES Phenytoin The extract at this dose didn t abolish the hind limb activity methanolic model extension, but reduced the mean recovery time from convulsion. Antidepressant Whole part/ 50, 100 mg/kg/TST and FST Imipramine The result showed that only chloroform fraction in this doses activity ethanolic model or fluoxetine significantly reduced the immobility time in both FST & TST. Anxiolytic activity Aerial part/ 200 mg/kg/EPM model Diazepam The result showed that ethyl acetate fractions at this dose reduced ethanolic the neuromuscular co-ordination indicative of the muscle relaxant activity. Anxiolytic activity Flower part/ 100, 200, 400 mg/kg/EPM Diazepam The result demonstrated that the flower extract of plant exerted ethanolic model anxiolytic effect in mice on EPM. C. pluricaulis Learning behavior Whole part/ 100 mg/kg/passive Piracetam The extract exhibited potent memory enhancing effects. and memory ethanolic avoidance paradigms and enhancement active avoidance test activity Learning behavior Root part/ 200 mg/kg/passive Piracetam The result shown that higher retension was observed with plant extract and memory ethanolic avoidance paradigms and as compared with standard drug. enhancement active avoidance test activity C. pluricaulis Anti thyroid Root part/ 0.4 mg/kg/ Methimazole The result indicated that extract inducing inhibition in activity ethanolic radioimmumoassay thyroid function was primarily mediated through T4 to T3 conversion. technique Antiulcer activity Whole part/ 375, 750 mg/kg/gastric Sucralfate The result was found due to augmentation of mucosal defensive ethanolic ulcer model factors like mucin secretion rather than acid pepsin. C. pluricaulis Antiobsessive Whole part/ 200, 400 mg/kg/rota rod, Fluoxetine, The result shown that extract can modulate serotonin or activity methanolic hole board test diagepam dopaminergic levels. C. pluricaulis Neuroprotective Whole part/ 150 mg/kg/EPM, MWM Rivastigmine The result shown that when scopolamine is induced, the activity aqueous model tartrate extract may exert its potent enhancing activity through anti-AChE and antioxidant action. C. Neuroprotective Whole part/ 150 mg/kg/ EPM, MWM Rivastigmine The result shown that when aluminium chloride is induced, the pluricaulis activity aqueous model tartrate extractpossesses neuroprotective potential, thus validating its use in alleviating toxic effects of aluminium. C. pluricaulis Hepatoprotective Leaves part/ 200, 400, 600 mg/kg/ Silymarine The result shown that extract possesses significant activity ethanolic thioacetamide induced hepatoprotective property in thioacetamide induced liver toxicity in liver damage in rats rat model. Escherichia coli C. pluricaulis Anti-bacterial Whole part/ ATCC Tetracycline The result shown that extract is more active against Staphylococcus Escherichia coli Staphylococcus aureus. activity methanolic 8739, in comparision to aureus 6538 / Cup plate Model C. pluricaulis A W 150 R T ntiviral activity hole part/ mg/kg/scopolamine ivastigmine he result shown that β extract reduced the increased RNA A PP aqueous induced increased tau proteinβ and m levels of tau and levels followed by reduction and amloid precursor in A levels compared with scopolamine treated group. protein C. pluricaulis Nootropic activity Whole part/ 250, 500 mg/kg/Cook and Piracetam The result shown that extract is less effective than other ’ Shankhpuspi Evolvulus alsinoides ethanolic Weidley s pole climbing species of ( ). model DPPH 1 1 2 MES TST FST EPM : , -diphenyl- -picryl- hydrazyl, : maximal electroβ shock, : tail suspension test, : forced swim test, : elevated plus maze, MWM: morris water maze, CNS: central nervous system, A PP: amyloid precursor protein.

C. pluricaulis major contributors for the traditional therapeutical effects of The physical analysis of are given in Table C. pluricaulis . Other compounds such as proteins, gum and 5[30]. C. pluricaulis mucilages have been also reported in . 5.1. Physical analysis Parul Agarwal et al./Asian Pac J Trop Biomed 2014; 4(3): 245-252 249 Table 5 Table 6 C. pluricaulis C. pluricaulis Physical analysis of . Preliminary phytochemical test of ethanolic extracts of Parameters Values (leaves). Foreign matter analysis (1.1350依0.1407)% w/w Phytochemical tests Results Loss on drying (11.8500依0.7188)% w/w Test for alkaloids + Total ash (7.1300依0.3371)% w/w Test for glycosides + Acid insoluble ash (3.9500依0.3905)% w/w Test for carbohydrates + Water soluble ash (1.9500依0.1528)% w/w Test for saponins - Swelling index Absent Test for fats and oils - Foaming index Less than 100 Test for flavonoids + Phosphate 1% solution 7.22 Test for tannis and phenolic compounds - Phosphate 10% solution 7.53 Test for protein + Extractive value Hot extraction (w/w) Test for gums and mucilage + Petroleum ether (0.8000依0.0288)% Test for steroids + Chloroform (0.9250依0.0866)% +: presence of compound; -: absence of compound. Acetone (1.0750依0.1507)% Methanol (2.0000依0.0803)% Hydro-alcohol (4.9750依0.3744)% 6. Current Ayurvedic formulation Aqueous (16.9300依1.0760)% Ethanol (0.1189依0.0321)% 5.2. Phytochemical test Many medicines are currently available in India, in which after mixing numerous plant extracts or powders with two Medhya C. pluricaulis The preliminary phytochemical test of ethanolic extracts of or three plants including Ayurvedic C. pluricaulis [35] (leaves) are given in Table 6[31,32]. formulation is developed . Some preparations have been subjected to clinical trials. Examples include: 5.3. Phytochemical structures 6.1. Remem (Zydus Industries, India) C. pluricaulis The phytochemical structures present in are [33,34] The syrup and tablets include the following 10 species: given in Table 7 . Centella asiatica C. asiatica , Celastrus paniculatus C. ( ) ( paniculatus , C. pluricaulis, Asparagus racemosus A. ) ( racemosus , Acorus calamus A. calamus , Embelia ribes E. ) ( ) ( ribes , Tinospora cordifolia, Achyrantes aspera, Terminalia )

Table 7 C. pluricaulis. Phytochemical structures present in

Chemical name CH 2 OH Structure H O H H HO H

D-glucose OH OH H OH

D-glucoseHO is also known as dextrose or grape sugar. It is a simple monosaccharide found in the plants

OH HO O O OH O Maltose HO OH HO OH α Maltose is also known as maltobiose or malt sugar, a disaccharide formed from two units of glucose joined with bond OH O OH

CH3 Rhamnose OH OH Rhamnose is a naturally occurring deoxy sugar Sucrose Sucrose is the organic compound commonly known as table sugar and sometimes called saccharose HO H N O C H O onvolvine O O

Convolvine is an alkaloid, present in the leaves and stem of this species Parul Agarwal et al./Asian Pac J Trop Biomed 2014; 4(3): 245-252 250 Table 7, continued C. pluricaulis Phytochemical structures present in . CH2OH CH2OH CH2OH H O H H O H H O H H H H OH H OH H OH H Starch O O O O H OH H OH H OH Starch or amylum is a carbohydrate consisting of a large number of glucose units joined by glycosidic bonds CHH C 33 OH O O N convoline O O O

Myristic acid OH Myristic acid also called tetradecanoic acid, is a common saturated fatty acids O

Palmitic acid HO Palmitic acid also called hexadecanoic acid, is the most common fatty acid found in animals, plant and microorganism O O OH

Scopoletin O

Scopoletin is a coumarin found in root of plants in the genus scopolia O

OH

Linoleic acid

6 Linoleic acid belongs to one of the twoOH families of esential fatty acids; it is an unsaturated n- fatty acid

HO O

OH Kampferol HO O Kampferol is a natural flavonol, a type of flavonoid; kaempferol have a wide range of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial, anticancer, cardioprotective, neuroprotective, antidiabetic, anti- osteoporotic, estrogenic/antiestrogenic, anxiolytic, analgesic and antiallergic activities

H β H -sitosterol H H HO β -sitosterol is one of several phytosterols (plant sterols) with chemical structures similar to that of cholesterol. It is used in

treating hypercholesterolemia OH

Cetyl alcohol Cetyl alcohol, also known as 1- hexadecanol and palmityl alcohol, is a fatty alcohol chebula Saussurea lappa . cordifolia, Operculina turpethum, Pavonia odorata, and [35] Caryophyllus aromaticus Foeniculum vulgare[35]. 6.2. Tirukati and 6.3. Ayumemo (Welexlabs, India) Tirukati Bacopa monnieri, C. 13 pluricaulis, C.includes asiatica, A. species: racemosus, Valeriana wallichii, Ayumemo C. asiatica, C. pluricaulis, 5 Rueraria tuberosa, Saussurea lappa, E. ribes, Tinospora C. paniculatus,consists Withania of somnifera,species: A. racemosus . and [35] Parul Agarwal et al./Asian Pac J Trop Biomed 2014; 4(3): 245-252 251 6.4. Abana (The Himalaya Drug and Co, India) Acknowledgements

C. asiatica, C. The syrup and tablets include 19 species: The authors are thankful to the authorities of Bundelkhand pluricaulis, C. paniculatus, Balsamodedron mukul, Ocimum University Jhansi for providing support to the study and other sanctum, Nardostachys jatamansi, Piper longum, Carum necessary facility like internet surfing, library and other copticum, Zingiber officinalis, Cyperus rotundus, A. calamus, technical support to write a review article. E. ribes, Syzygium aromaticum, Santalum album, Elettaria cardamomum, Foeniculum vulgare, Rosa damascena, Cinnamomum cassia Crocus sativus . Comments and [35] 6.5. Tejras (Sandu Brothers, India) Background C. pluricaulis This is a review paper on the benefits of as an C. asiatica, The syrup consists of the following 12 species: alternative medicine for many diseases. The pharmacological C. pluricaulis, C. paniculatus, Eclipta alba, Cynodon effects exhibited by this plant have been elaborated in depth dactylon, A. racemosus, Withania somnifera, Nardostachys with citations from studies that have been conducted using jatamansi, A. calamus, Zingiber officinalis Vetiveria and this Ayurvedic plant. zizanoides . [35] Research frontiers 6.6. Shankhapushpi (Unjha Pharmacy, India) There is no lab experiment being done in this manuscript since it is a review paper. However, the author cited latest C. pluricaulis, C. asiatica, The syrup includes 6 species: and recent publications on works done in this particular Nardostachys jatamansi, Nepeia hindostana, Nepeia elliptica field, in which bring the readers to the recent analytical Onosma brateatum . and [35] approach for pharmacological potential of this plant. Related reports 7. Toxicity The author cited different papers in his manuscript C. pluricaulis to support the therapeutic potential of in C. microphyllus The LD50 of the whole extract of by oral traditional medicine. Past studies mostly presented the in vitro in administration was found to be 1 250 (1 000-1 400) mg/kg. Mice pharmacological activities of this plant done and vivo treated with the extract showed a sedative effect at doses . greater than 200 mg/kg and reflected a moderate to marked Innovations and breakthroughs decrease in locomotor activity which lasted 1-2 h. The decrease in motor activity due to spontaneous motor activity This review paper is one of its own in which it summarizes C. pluricaulis was observed during the study. At a higher dose (more than 1 any research that have been conducted on g/kg) animals died due to respiratory distress[36]. specifically in medicinal field. It is a good source of literature survey for researchers who intended to do studies in this particular field, and use this plant. 8. Conclusion

Applications The present review discusses the plant profile, This paper could be applied by most Ayurvedic pharmacognosy, pharmacology, phytochemistry of the practitioners in their medication activities to treat patients C. pluricauli herb, . Glycosides, flavonoids, alkaloids, with different types of diseases. carbohydrates, steroids, proteins, gums and mucilage Peer review compounds are commonly present in this species. Pharmacological studies carried out on crude extracts and This paper is a good review paper on Ayurvedic and C. pluricaulis pure metabolites provided pragmatic documents for its pharmacological activities of . Citations used traditional uses, and have revealed this herb to be a valuable are also a good resources for reviewing and very informative source for medicinally important molecules. to all the Ayurvedic and traditional practitioners.

Conflict of interest statement References

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