IJPCBS 2013, 3(2), 233-241 Elizabeth Margaret et al. ISSN: 2249-9504

INTERNATIONAL JOURNAL OF PHARMACEUTICAL, CHEMICAL AND BIOLOGICAL SCIENCES

Available online at www.ijpcbs.com Review Article

AMRUTHAVALLI ( CORDIFOLIA) MULTIPURPOSE REJUVENATOR PV. Neeraja and Elizabeth Margaret* Department of Botany, St. Ann’s College for Women, Mehdipatnam, Hyderabad-500 028, Andhra Pradesh, India.

ABSTRACT The last decade has seen a global upsurge in the use of traditional medicine (TM) and complementary and alternative medicines (CAM) in both developed and developing countries. Various forms of traditional, complementary and alternative medicines are playing a progressively more important role in health care globally and therefore their safety, efficacy, and quality control are important concerns today. Tinospora cordifolia (Willd.) Miers. (Amruthavalli or Guduci), is one of the most versatile rejuvinative herbs widely used as a traditional medicine. It is mentioned in various classical texts of Indian Medicinal Systems and is cultivated throughout the Indian subcontinent and China. The therapeutic efficacy makes for its extensive usage in various systems of medicine. Pre clinical and clinical pharmacological studies affirm the importance of this herb. The notable medicinal properties are anti-diabetic, anti-periodic, anti-spasmodic, anti-inflammatory, anti-arthritic, anti-oxidant, anti-allergic, anti- stress, anti-leprotic, anti-malarial, hepatoprotective, immunomodulatory and anti-neoplastic activities. The principle constituents present in the are alkaloids, diterpenoid lactones, glycosides, steroids, sesquiterpenoid, phenolics, aliphatic compounds and polysaccharides. The present paper reviews the pharmacological and phytochemical aspects of the herb and its usage in different medicinal systems. However, the molecular mechanism of these activities of Tinospora cordifolia for its medicinal properties is to be elucidated.

Keywords: Tinospora cordifolia, Diterpenoid, Glycosides, Alkaloids.

INTRODUCTION hepatitis, skin diseases, and anemia. In Tinospora cordifolia (Wild.)Miers ex Hook.F compound formulations, guduchi is used & Thems (Family: ) clinically to treat jaundice, rheumatoid commonly known as Guduchi is an Indian arthritis, and diabetes. Hindi, the plant is medicinal plant and has been used in commonly known as Giloya, which is a Ayurvedic preparations for the treatment of Hindu mythological term that refers to the various ailments throughout the centuries. heavenly elixir that have saved celestial Ancient Hindu physicians prescribed it for beings from old age and kept them eternally gonorrhea. European medical men in India young. became interested in the tonic and diuretic properties of T. cordifolia. Today, the drug The genus Tinospora and a tincture prepared from it have Tinospora is one of the important genera of received official recognition in the Indian the family, consisting of about 15 species. Pharmacopoeia. It has been used to treat Some medicinally important species general weakness, fever, dyspepsia, includes T. cordifolia, T. malabarica, T. dysentery, gonorrhea, secondary syphilis, tomentosa, T. crispa, T. uliginosa, etc. urinary diseases, impotency, gout, viral

233

IJPCBS 2013, 3(2), 233-241 Elizabeth Margaret et al. ISSN: 2249-9504

Species - Tinospora cordifolia (Willd.) secondary growth resulting in the Miers. Family: Menispermaceae formation of 10 to 12 wedged shaped (moonseeds) external xylem which is surrounded by semi Common Name(s): Guduchi , amrita –circular strip of phloem alternating with (Sanskrit), giloe , gulancha (Bengali), giloya medullary rays. Phloem cells contain (Hindi), gado , galo (Gujarati), duyutige , calcium oxalate crystals. Presence of two teppatige (Telugu), heartleaf moonseed layered cambium. Xylem consists of vessels, (English). tracheids, xylem parenchyma and fibres. Distribution: Tinospora cordifolia is a large Pith is parenchymatous which contain deciduous climbing shrub found throughout starch grains.20 India and also in Srilanka, Bangladesh and China.6 Photochemistry A large number of compounds have been Morphology of the Plant reported from the aerial parts and roots of T. cordifolia is a glabrous, succulent, woody T. cordifolia. In the early 1900s, giloin, climbing shrub native to India. It is also gilenin, and gilosterol, as well as the bitter found in Burma and Sri Lanka. It thrives principles columbin, chasmanthin, and well in the tropical region, often attains a palmarin, were identified in the plant. Apart great height, and climbs up the trunks of from these reports also suggests the large trees. The stem is gray or creamy- presence of wide range of alkaloids11,21 white, deeply cleft spirally and steroids, glycosides, polysaccharides, longitudinally, with the space between Berberine17, Sesquiterpenoid.22,15 Detail spotted with large rosette-like lenticels. The photochemistry of the plant is presented in wood is white, soft, and porous, and the the table.1. freshly cut surface quickly assumes a yellow tint when exposed to air. Leaves are simple, Medicinal Systems alternate, exstipulate, long petiolate, Ayurveda chordate in shape showing multicoated Guduchi finds its mention in various reticulate venation. Long thread-like aerial classical referential texts of Ayurvedic roots come up from the branches. Flowers System of Medicine like Charak, Sushrut, are small and Unisexual. Male flowers are in Ashtang Hridayaand , Bhava Prakash and clusters female flower are solitary. Six Dhanvantari Nighantu with its synonymic sepals arranged in two whorls of three each. names like Amara, Amritvalli, Chin- Six petals arranged in two whorls, they are narrhuha, Chinnodebha and Vatsadani etc. obovate and membranous. Aggregate fruit In Sushurta Samhita, it is mentioned under is red, fleshy, with many drupelets on thick “Tikta-Saka Varga” and claimed to be useful stalk with sub terminal style scars, scarlet in treating Kustha (Leprosy), Maha-jvara coloured.16, 4 (High fever), Svasa (Asthma) and Aruchi (anorexia). Charak Samhita and Ashtang Microscopic Details Hridaya, it has been indicated in diseases Cork- Older stem comprises of an outer like Kamala (Jaundice), Jvara (Fever) and zone of thick walled brownish compressed Vat Rakta (Gout), etc. It is considered as a cells and an inner zone of thin walled astringent, diuretic and potent aphrodisiac colorless, tangentially arranged cells.The and curative against skin infections, cork tissue is broken at some places due to jaundice, diabetes and chronic diarrhea lenticels. Cortex-Cortex is multilayered, according to Bhava Prakash. Medicinal outer few layers are made up of irregular, properties of Tinospora is detailed in chlorenchymatous cells while cells of inner Dhanvantari Nighantu. It is a traditional cortex is made up of polygonal cells that belief among the Ayurvedic practitioners contain starch grains which are simple and that Guduchi Satva obtained from Guduchi ovoid. Many secretary cells are found plant growing on Neem tree (Azadirachta scattered in the cortex.Pericycle shows the indica) is bitter, more efficacious and is said presence of fibers. Vascular Bundles- to incorporate the medicinal virtue of Neem Tinospora cordifolia shows anomalous also.

234

IJPCBS 2013, 3(2), 233-241 Elizabeth Margaret et al. ISSN: 2249-9504

Properties: Guna:- Guru, Snighda The Muslim tribals of Rajouri, Jammu Rasa:- Tikta Kashaya (Tawi) comprising Gujjar and Backwals Veerya:- Ushna used the plant in bone Fracture.32 Vipaka:- Madhura Karma (Action): Tridoshahara(Balances Pharmacological studies vitiated Tridoshas) Kushtaghna, Analgesic activity Vedanastaapana(Cures skin diseases and An aqueous extract of Tinospora cordifolia relieves pain)Jwaraghna(reduces fever), decreased bronchospasm in guinea pigs, Vrishya (aphrodesiac), decreased capillary permeability in mice Rejuvenator (Rejuvenates body systems), and reduced the number of disrupted, mast Formulations: Guduchyadi churna, Guduchi cells in rats. taila,Dashmoolarishtha, Sanjivani vati, Kanta-kari avaleha, Chyavanaprasha, Anticancer activity Guduchi sattva, Brihat guduchi taila, A formulation containing Tinospora Stanyashod-hana kashaya churana, cordifolia, Asparagus racemosus, Withania Punchnimba churana, Guduchi ghrita, somnifera and Picrorrhiza kurrooa markedly Amritaguggulu, Amritashtaka churna, etc. inhibited the suppression of chemotactic activity and production of interleukin-1 and Unani System tumour necrosis factor induced by the In Unani System, mostly “Sat Giloe” is carcinogen ochratoxin in mouse incorporated in the preparations. macrophages.19 “ArqGiloe” prepared from the fresh plant is considered a febrifuge, while “Arq Maul Antineoplastic activity Laham Mako-kashiwala” is a general tonic. Aqueous, methanolic and dichloromethane extracts of Tinospora cordifolia showed Folklore dose-dependent increases in lethality to T. cordifolia finds a special mention for its HeLa cells in vitro. The most potent activity use in tribal or folk medicine in different was found in the dichloromethane extract. parts of the country. Some of the important uses mentioned are given below: Antioxidant activity Naugarh and Chakia Block of Varanasi An extract of Tinospora cordifolia reduced district, Uttar Pradesh (Baiga Tribals)- the toxicity induced by free radicals and Guduchi (T.cordifolia) stem paste along with inhibited lipid peroxidation and the roots paste of Bhatkatiaya (Solanum generation of superoxide and hydroxyl surattense) are made in to pills, that is used radicals in vitro. It reduced the toxic side to treat of fever for three days.29 effects of cyclophosphamide in mice as shown by the total white blood cell count, Bombay (Fishermen) use T. cordifolia as bone marrow cellularity and esterase- drug in the treatment of fever, jaundice, positive cells. It also partially reduced chronic diarrhea and dysentery.28 elevated lipid peroxides in serum and liver, as well as alkaline phosphatase and Khedbrahma (Tribes) of North Gujarat glutamine pyruvate transaminase18,19. use the plant leafy vegetable. Powdered root and stem bark of T. cordifolia with milk Antistress activity is used to treat cancer; decoction of root is An ethanolic extract of the roots of used as cure for dysentery and diarrhea.7 Tinospora cordifolia normalized stress- Jammu (J & K) and Bigwada (Rajasthan) induced biochemical changes in Decoction of the stem as cure high fever norepinephrin Antistress activity24. 5Bhuvneshwar (Orissa) use the warm juice of root of T.cordifolia orally for the Antiulcer activity treatment of fever. An ethanolic extract of the roots of Decoction of leaves along with honey is Tinospara cordifalia, in combination with administered orally for fever by the people Centella asiatica, afforded significant of Patiyala (Punjab). protective action against restraint stress-

235

IJPCBS 2013, 3(2), 233-241 Elizabeth Margaret et al. ISSN: 2249-9504 induced ulcer formation. The activity was reactions were noted when T. cordifolia comparable to diazepam in rats.25 stem extract was administered to rabbits up to the highest oral doses of 1.6 g/kg, and in Antidiabetic rats at doses of 1,000 mg/kg of the whole Reports suggest that alcoholic extraction of plant extract. However, a 40% mortality the stem favors endogenous insulin resulted after mice were given 500 mg/kg secretion.14 body weight of an extract of the stems of Tinospora. Urinary Calculi Water extract of the stem was Conservation Status experimentally evaluated for dissolution of Arrow-head is listed as vulnerable. urinary calculi.23 This species is eligible for listing as vulnerable under the Environment Products of Tinospora cordifolia Protection and Biodiversity Conservation Shilpa Pravang-Sexual Vitality. Act 1999 (Cwlth) (EPBC Act) as, prior to the Guduchi Tablets –General infection, commencement of the EPBC Act, it was immune disease, Hepatitis, Arthritis and listed as vulnerable under Schedule 1 of the anti-cancer. Endangered Species Protection Act 1992 Madhu Mehari-Dryness of mouth, relieves (Cwlth). Arrow-head Vine is also listed as frequent urination and maintains the vulnerable under the Threatened Species normal sugar levels. Conservation Act 1995 (NSW) and the Mussaffen-Blood purifier and as a check for Nature Conservation (Wildlife) Regulation skin diseases. 2006 (Queensland). Rebuild-Anti-stress and anti-oxidant properties. CONCLUSION Septilin-check the respiratory infection The therapeutic efficacy of Tinospora Tonplex-Increase the immunity and vitality. cordifolia makes it a primary drug in Indian Joint Muscle Excellence Tablets-Eliminate Medicinal System. This has also been the toxins of joints. established by the clinical studies carried Natadadrol-Androgen builder. out for different aliments.Thes studies place this drug a novel candidate and drug Toxicology development for the treatment of disease of There is little known about the toxicology of all kinds. T. cordifolia in humans. No adverse

Fig. 1:Tinospora cordifolia plant Fig. 2: Inflorescence of T.cordifolia Fig. 3: Plant with Fruits (druplets)

236

IJPCBS 2013, 3(2), 233-241 Elizabeth Margaret et al. ISSN: 2249-9504

Fig.4: Old Bark of the Plant Fig. 5: Bark powder Fig. 6: Fruits (druplets)

Structures of the active Principle Diterpenoid

Structure of Furanolactone

Chasmanthin Tinocordifolin

Tinocordifolioside cadinane

237

IJPCBS 2013, 3(2), 233-241 Elizabeth Margaret et al. ISSN: 2249-9504

Alkaloids

Berberine Tembetarine

Choline Isocolumbin

Columbin Tinosporasid

Jatrorrhizine Palmatine Magnoflorine

238

IJPCBS 2013, 3(2), 233-241 Elizabeth Margaret et al. ISSN: 2249-9504

Glycosides

Cordifolioside Tinocordiside

N-Formylannonain N-Methyl-2-pyrrolidine H-droxymustakone

Syringin

239

IJPCBS 2013, 3(2), 233-241 Elizabeth Margaret et al. ISSN: 2249-9504

Table 1: Showing the principle component of each part of the plant Plant Part Type of Compound Active Principle Choline,Tinosporin 12 Alkaloids Isocolumbin,Palmatine, Tetrahydropalmatine, Magnoflorine Diterpenoid Furanolactone Root Clerodane derivatives, Dihydroxy diepoxy – cleroda, Lactones Tinosporin, Tinosporides 27 Miscellaneous Jatrorrhizine Compounds Alkaloids Berberine, Palmatine, Tembetarine, Magnoflorine, Choline Norclerodane glucoside, Furanoid diterpene glucoside, Tinocordiside, Glycosides Tinocordifolioside Syring, Syring-apiosylglycoside, Palmatosides, Crdifoliside A,B C , D& F13

Diterpenoids Furanolactone 2

Clerodane deravative, Dihydroxy diepoxy- cleroda, Tinosporon, Tinosporides, Lactones Stem Jateorine, Columbin Steroids Β-Sitostrerol,Sitosterol,20βHydroxy ecodysone, MakisteroneA, Giloinsterol Sesquiterpenoid Tinocordifolin Diterpenoids Furanolactone7 ,31 Clerodane derivatives, tinosporon, Tinosporides, Lactones Jateorine 10 , Columbin

Aliphatic compounds Octacosanol, Heptacosanol, Nonacosan

Whole Miscellaneous Tinosporidine, Codifol,Cordifelone, Tinosporic acid, Gilonin, Giloin Plant Compounds Aerial Part Steroids β-Sitosterol, Sitosterol, 20β-Hydroxy ecdysone

REFERENCES 1. Ahmad M, Kazi AB, Karim R, 7. Bhatt RP and Sabnis SD. Khaleque A and Miah MAW. Contribution to the Ethnobotany of Structure of tinosporide, a furanoid Khedbrahma region of North diterpene from Tinospora cordifolia Gujarat J Econ Tax Bot Miers. J Bangladesh Acad Sci. 1987;9(1):139. 1978;2:25-30. 8. Bhatt RK, Hanuman JB and Sabata 2. Ahmad M, Khaleque A and Miah BK. A new clerodane derivative MAW. Structure of tinosporide, a from Tinospora cordifolia. new furanoid diterpene. Indian J Photochemistry. 1988;27:1212-6. Chem Sec B. 1978;16:317-8. 9. Bhatt RK and Sabata BK. Furanoid 3. Akhila A, Rani K and Thakur RS. diterpene glucoside from Tinospora Biosynthesis of the clerodane cordifolia. Phytochemistry. furano-diterpene lactone skeleton in 1989;28:2419-22. Tinospora cordifolia. 10. Bhatt RK and Sabata BK. Structure Phytochemistry. 1991;30:2573-6. of tinosporide: Its identity in all 4. Anonymous wealth of India: Raw respects with jateorin (1S, 2S, 3R, materials, Vol X. New Delhi: CSIR, 4R, 5R, 8S, 10R,12S)-4-hydroxy- 1976. 2,3:15,16-diepoxycleroda-13(16), 5. Anonymous. An Appraisal of Tribal- 14-dieno-17,12:18,1-biscarbolact- Folk Medicine, Central Council for one. Indian J Chem Sec. Research in Ayurveda & Siddha, 1990B;29:521-4. New Delhi, 1999. 11. Bisset NG and Nwaiwu J. Quaternary 6. Raghu AV, Geetha SP, Martin G, alkaloids of Tinospora species. Balachandran I and Ravindran PN. Planta Medica. 1983;48:275-9. In vitro cell Dev Biol Plant. 12. Chatterjee A and Ghosh S. 2006;42:584-588. Tinosporin, the furanoid bitter

240

IJPCBS 2013, 3(2), 233-241 Elizabeth Margaret et al. ISSN: 2249-9504

principle of Tinospora cordifolia. Sci the field. Sci Res (Dacca). and Culture 1964;1:177-83. (Calcutta,India).1960;26:140-1. 23. Rai M and Gupta SS. Experimental 13. Gangan VD, Pradhan P, Sipahimalani Evaluation of Tinospora cordifolia AT and Banerji A. Cordifolisides A,B, (Guduchi) for dissolution of urinary C: Norditerpene furan glycosides calculi. J Res Indian Med. 1967; from Tinospora cordifolia. 2(1):115. Phytochemistry. 1994;37:781-6. 24. Sarma DNK, Khosa RL, Chaurasia 14. George. J Sci Industrial Res. JPN and Shai M. Antistress Activity 1947;6B:42. of Tinospora cordifolia and centella 15. Ghosal S snd Vishwakarma RA. asiatica Extracts, Phytotherpy Tinocordiside, a NewRearranged Research. 1996;10:181. Cadinane Sesquiterpene Glycoside 25. Sarma DNK, Khosa RL, Chaurasia from Tinospora cardifolia. J Nat JPN and Shai M. Antiulcer Activity of Prod. 1997;60:839-41. Tinospora cordifolia Meirs and 16. Kirtikar KR and Basu BD. Indian Centella asiatica Linn. Extracts; Medicinal , Vol 2(Lalit Mohan Phytotherapy Research. 1995;9:589. Basu, leader Road, Allahabad), 26. Sarma DNK, Khosa RL and Sahai M. 1933;77. Isolation of Jatrorrhizine from 17. Kumar S, Verma NS, Pande D and Tinospora cordifolia Roots. Planta Srivastava PS. In vitro regeneration Med. 1995;61:98-9. and screening of berberine in 27. Sarma DNK, Padma P and Khosa RL. Tinospora cordifolia. J Med Arom Constituents of Tinospora cordifolia Plant Sci .2000;22:61. root. Fitoterapia. 1998;69:541-2. 18. Maryamma K.I Ismail PK, 28. Shah GL. Some Economically Manomohan CB and Rajan A. important plants of Salsette Island Ameliorating effect of amruthu near Bombay, J Econ Tax (Tinospora cordifolia ) in Bot,5(1984)753. rth Gujarat, J Econ aflatoxicosis of ducks, J Vet Anim Sci. Tax Bot. 1984;5:753. 19990;21(2):93. 29. Singh K and Maheshwari JK. 19. Methews S and Kuttan G. Traditional Phytotherapy Amongst Antioxidant activities of Tinospora the Tribals of Varanasi District, U. P, cordifolia and its usefulness in the J Econ Tax Bot. 1983;4(3):829. amelioration of cyclophosphamide 30. Swaminathan K, Sinha UC, Bhatt RK, induced toxicity. J Exp Clin Cancer Sabata BK and Tavale SS. Structure Res. 1997;16:407. of tinosporide, a diterpenoid 20. Nasreen S, Radha R, Jayashree N, furanolactone from Tinospora selvaraj B and Rajendran A. cordifolia Miers. Acta Crystallogr C. Assesment of quality of Tinospora 1989;45:134-6. cordifolia (Willd.) Miers. 31. Swaminathan K, Sinha UC and (Menispermaceae):Pharmacognosti Ramakumar S. Structure of cal and Phyto-Physicochemical columbin, a diterpenoid 21. Padhya MA. Biosynthesis of furanolactone from Tinospora isoquinoline alkaloid berberine in cordifolia Miers. Acta Crystallogr, tissue cultures of Tinospora Sect C, Cryst Struct Commun. cordifolia. Indian Drugs. 1989;C45:300-3. 1986;24:47-8. 32. Vir Jee, Dar GH, Kachroo and Bhat 22. Qudrat-I-Khuda M, Khaleque A and GM. Taxo-ethnobotanical studies of Ray N. Tinospora cordifolia I. the rural areas in district Rajouri Constituents of the plant fresh from (Jammu), J Econ Tax Bot. 1984;5:831.

241