Botanical Name— Tinospora cordifolia

Family- MENISPERMACEAE

Names in different language

Marathi : Ambarvel, Gulavela

Oriya : Gulochi, Gulancha
Hindi : Gibe, Gurach

Kannada : Arnryta balli, Ugani
Malayalam: Amrytu, Sittamrytu
Telugu : Tippa teega

Bengali : Giloe, Gulancha

Punjabi : Batindu, Gibogularich
Gujarati : Gado, Gulo

Sikkim : Gurjo

Tamil : Amrida Valli, Pattigai Silam

Tinospora cordifolia

Tinospora cordifolia

Introduction—

It is one of the non-controversial drug used in Ayurvedic medicine. It used for Grãhi, Väta hara,Dipaniya,Kapha-Raktahara and Vibandhahara , Medhya Rasayãnas

Morphology

Large succulent climbing shrubs or deciduous vines about 15-25 m long. Stem striate, with scattered lenticels which are often 4 fid, fleshy, puberulous and green when young, later membranous and glabrous, with long aerial roots. Leaves simple, alternate, broadly ovate, orbicular or subrotund, 7-16 x 4.5-12 cm across, base subcordate or abruptly truncate, margin entire, apex suddenly acutely acuminate, chartaceous, membranous, thin, green, sparingly pubescent above, paler pilose with glandular patches beneath, strong basal veins 5-7, impressed above and prominent beneath, lateral veins 1-2 pairs, veinlets fine and close, petiole puberulous, about 4-12 cm long. Inflorescence axillary on old leafless stems, slender, pseudo-racemose cymes, usually appearing when the deciduous plant is leafless, about 3-12 cm long, pedunculate. Flowers unisexual, greenish yellow, pedicellate. Male flowers, pedicels slender, glabrous about 3-4 mm long, sepals 6, in 2 series, inner series larger, elliptic, apex obtuse, about 3-5 x 2-5 mm long, outer series smaller, about 1-1.5 mm long, free, imbricate, ovate, apex obtuse, petals 6, free, rhomboidal-ovate, 3-5 x 1-3 cm across, stamens 6, free, filaments clavate, about 3 mm long, anthers loculed, subextrorse, obliquely or longitudinally dehisced. Female flowers, pedicels about 4-10 mm long, sepals and petals similar as in male flowers, staminodes 6 about 1 mm long, carpels 3, ellipsoid, about 1.5-2 mm long, glabrous, style short, stigma lobed. Fruits drupes, obovoid or ellipsoid, glabrous, shining, bright orange or scarlet red when ripe, about 8-15 mm across, carpophores about 2-3 mm long, stalks about 8-10 mm long, pericarp thin, style scar subterminal, endocarp bony, very thin, subrotund or broadly elliptic about 7-9 x 5-6 mm across, tuberculate with small aperture. Seeds curved, endospermic, cotyledons flattened, radicle short.

Distribution

Local Distribution: Andhra Pradesh, Arunachal Pradesh, Assam, Bihar, Daman & Diu, Goa, Karnataka, Kerala, Maharashtra, Manipur, Meghalaya, Mizoram, Odisha, Sikkim. Global Distribution: Asia: Bangladesh, Cambodia, China, India, Myanmar, Nepal, Sri Lanka, Thailand, Vietnam.

Medicinal Properties:

Tinospora cordifolia is widely used medicinal plant in Ayurvedic system for its general tonic, antiperiodic, anti-spasmodic, anti-inflammatory, antipyretic, anti-arthritic, anti-lepritic, anti-allergic and anti-diabetic properties ³³.

The plant is used to improve the immune system and the body resistance against infections. The root of this plant is known for its anti-stress and anti-malarial activities. The stem is bitter, stomachic, diuretic, stimulates bile secretions, allays thirst, enriches the blood and cures jaundice. The extract of the stem is useful in skin problems. The root and stem of Tinospora cordifolia is prescribed in combination with other drugs as an antidote to snakebite and scorpion. ³³ The plant is also used in the treatment of wounds, pneumonia, asthma and cough. Tinospora cordifolia has anti-cancer, immune stimulating, nerve cell protecting, anti-diabetic, cholesterol-lowering and liver-protective actions. Tinospora cordifolia is also responsible for decreasing the tissue damage caused by radiation, the side effects of some forms of chemotherapy and speeding healing of diabetic foot ulcers ³⁴.

Medicinal uses, Adverse effects,Research & Pharmacology

Immunomodulatory property

The immuomodulatory property of Tinospora cordifolia is well documented.– Active compounds -hydroxymustakone, N-methyl--pyrrolidone, N-formylannonain, cordifolioside A, magnoflorine, tinocordiside and syringin has been reported to have potential immunomodulatory and cytotoxic effects.,– They have been reported to function by boosting the phagocytic activity of macrophages, production of reactive oxygen species (ROS) in human neutrophil cells, enhancement in nitric oxide (NO) production by stimulation of splenocytes and macrophages indicative of anti-tumor effects. Aqueous Tinospora extracts has been also reported to influence the cytokine production, mitogenicity, stimulation and activation of immune effector cells. In mice, Tinospora cordifolia extracts has been shown to result in up-regulation of IL- cytokine, resulting in acute reactions to injury, inflammation, activation of cytotoxic T cells, and B cell differentiation. Active compounds in aqueous extracts like alkaloids, di-terpenoid lactones, glycosides, steroids, sesquiterpenoid, phenolics, aliphatic compounds or polysaccharides in experimental rat model have been reported for their cytotoxic action. Dry stem crude extracts of Tinospora cordifolia with a polyclonal B cell mitogen, G-A on binding to macrophages have been reported to enhance immune response in mice by inducing secretion of IL-, together with activation of macrophages. Reports on Tinospora cordifolia in prevention of oxidative damage also exist. The (,)-alpha-d-glucan (alpha-d-glucan), derived Tinospora cordifolia have been shown to activate human lymphocytes with downstream synthesis of the pro- and anti-inflammatory cytokines, in vitro. Synergistic effects of compounds in the immunomodulatory activity of Tinospora cordifolia are reported.

Tinospora cordifolia

Anti-diabetes property

The stem of Tinospora cordifolia is widely used in the therapy of diabetes by regulating the blood glucose in traditional folk medicine of India. It has been reported to mediate its anti-diabetic potential through mitigating oxidative stress (OS), promoting insulin secretion and also by inhibiting gluconeogenesis and glycogenolysis, thereby regulating blood glucose. Alkaloids, tannins, cardiac glycosides, flavonoids, saponins, and steroids as the major phytoconstituents of Tinospora cordifoliahave been reported to play an anti-diabetic role.

The isoquinoline alkaloid rich fraction from stem, including, palmatine, jatrorrhizine, and magnoflorine have been reported for insulin-mimicking and insulin-releasing effect both in vitro and in vivo. Oral treatments of root extracts have been reported to regulate blood glucose levels, enhance insulin secretion and suppress OS markers. Initiation and restoration of cellular defence anti-oxidant markers including superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione (GSH), inhibition of glucose -phosphatase and fructose , -diphosphatase, restoration of glycogen content in liver was reported in in vitro studies. The crude stem ethyl acetate, dichloromethane (DCM), chloroforms and hexane extracts of Tinospora cordifolia inhibited the enzyme's salivary and pancreatic amylase and glucosidase thus increasing the post-prandial glucose level and finds potential application in treatment of diabetes mellitus.

The root extract has been reported to decrease the levels of glycosylated hemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and vitamin E diabetic rats. Oral administration of Tinospora cordifolia extract in “Ilogen-Excel” formulation (Ayurvedic herbal formulation) composed of eight medicinal plants including Curcuma longa, Strychnos potatorum, Salacia oblonga, Tinospora cordifolia, Vetivelia zizanioides, Coscinium fenestratum, Andrographis paniculata, and Mimosa pudica is reported to reduce GSH and vitamin C in blood and urine glucose and lipids in the serum and tissues in alloxan diabetic rats with a subsequent decrease in body weight. Decreased concentration of GSH, GPx, and SOD, catalase activity is reported in heart and brain of diabetic rats. T. cardifolia root extract (TCE) has been reported to cause an increase in body weight, total hemoglobin and hepatic hexokinase and lowering hepatic glucose--phosphatase, serum acid phosphatase (ACP), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in diabetic rats thus having hypoglycemic and hypolipidaemic effect.

The protective effects of TCE were reported in presence of higher levels of anti-oxidant molecules and enzymes. TCE has been shown to significantly counterbalance the diabetes-associated OS in the maternal liver by lowering the levels of malondialdehyde and ROS and the increased levels of GSH and total thiols.

Tinospora cordifolia

Anti-toxic effects

Tinospora cordifolia extracts have been reported to scavenge free radicals generated during aflatoxicosis. It exhibited protective effects by lowering thiobarbituric acid reactive substances (TBARS) levels and enhancing the GSH, ascorbic acid, protein, and the activities of anti-oxidant enzymes viz., SOD, CAT, GPx, Glutathione S-transferase (GST) and glutathione reductase (GR) in kidney. Alkaloids such as a choline, tinosporin, isocolumbin, palmatine, tetrahydropalmatine, and magnoflorine from Tinospora cordifolia showed protection against aflatoxin-induced nephrotoxicity. Tinospora cordifolia stem and leaves extract has shown hepatoprotective effect in Swiss albino male mice against lead nitrate induced toxicity. Oral administration of plant extracts prevented the occurrence of lead nitrate induced liver damage. Decreased level of SOD, CAT and increased level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), ALP, and ACP were observed in mice suffering from lead toxicity. Synergistic administration of aqueous extract of stem and leaf along with the lead nitrate increased the activities of SOD and CAT and decreased the levels of AST, ALT, ALP, and ACP enzymes. Protective role of aqueous extract of stem and leaves of Tinospora cordifolia overcoming the toxic effects of lead is shown as its effects on the hematological values. Cyclophosphamide (CP) an anti-cancer drug has been reported to reduce the GSH content in both bladder and liver and lowered levels of cytokines Inerferon-γ and IL- an increased levels of pro-inflammatory cytokine TNF-α. This effect could be reversed on Tinospora cordifolia treatment indicating the role of Tinospora cordifolia in overcoming CP induced toxicities in cancer treatment.

Tinospora cordifolia

Tinospora cordifolia

Anti-arthritic, anti-osteoporotic effects

Single or synergistic formulations of Tinospora cordifolia with Zingiber officinale has been used in rheumatoid arthritis treatment in traditional medicine. Tinospora cordifolia have been reported to affect the proliferation, differentiation and mineralization of bone like matrix on osteoblast model systems in vitroand hence finds potential application as an anti-osteoporotic agent. Alcoholic extract of Tinospora cordifolia have been shown to stimulate the growth of osteoblasts, increasing the differentiation of cells into osteoblastic lineage and also increasing the mineralization of bone like matrix. Ecdysteroids isolated from the plant have been reported of protein anabolic and anti-osteoporotic effects in mammals. Beta-Ecdysone (Ecd) from Tinospora cordifolia extracts have been reported to induce a significant increase in the thickness of joint cartilage, induce the osteogenic differentiation in mouse mesenchymal stem cells and to relieve osteoporosis in osteoporotic animal models. Further -OH-β-Ecd isolated from Tinospora cordifolia has been reported of its anti-osteoporotic effects thus highlighting the role of Tinospora cordifolia in the treatment of osteoporosis and osteoarthritis.

 Tinospora cordifolia

Anti-HIV effects

TCE has been shown to demonstrate a decrease in the recurrent resistance of HIV virus thus improving the therapeutic outcome. Anti-HIV effects of TCE was revealed by reduction in eosinophil count, stimulation of B lymphocytes, macrophages and polymorphonuclear leucocytes and hemoglobin percentage thus, revealing its promising role of application in management of the disease.,

Tinospora cordifolia

Anti-cancer effects

The anti-cancer effects of Tinospora cordifolia are mostly studied in animal models. TCE have been shown to have a radioprotective role by significantly increase in body weight, tissue weight, testes-body weight ratio and tubular diameter and inhibit the harmful effects of sub-lethal gamma radiation on testes in male Swiss albino mice. In pre-irradiating mice, TCE significantly affected radiation induced rise in lipid peroxidation and resulted in the decline of GSH concentration in testes. Pre-treatment of HeLa cells by TCE have been shown to decrease the cell viability, increase LDH and decrease in GSH S-transferase activity. Dihydrotestosterone (DHT) in TCE has been reported to stimulate the growth and proliferation of Human LNCaP cells (which are androgen-sensitive human prostate adenocarcinoma cells). Androgenic compounds in TCE act via androgen receptor. Newly isolated compounds like (R, R)-R, R-dihydroxy-S, R: , -diepoxycleroda- (), , S: ,S-dilactone (ECD), a diterpenoid from Tinospora cordifolia has been reported for its chemopreventive potential in diethylnitrosamine (DEN) induced hepatocellular carcinoma (HCC) in rats by decreasing anti-oxidant activities via SOD, CAT and detoxification enzymes like GSH, GPx and subsequent increase in the activities of the hepatic markers ((Serum glutamic oxaloacetic transaminase)SGOT, (Serum Glutamic Pyruvate Transaminase) SGPT, LDH) and decreased serum transaminase level thus confirming its anti-tumor effects and promising application as a potent chemo preventive drug for HCC.

The radiosensitizing activity of DCM extract of Tinospora cordifolia has been reported in Ehrlich ascites carcinoma (EAC) mice enabling tumor-free survival via depletion of GSH and glutathione-S-transferase by elevated levels of lipid peroxidation and DNA damage to tumor cells.,, TCE hexane fraction has been shown to block the G phase in EAC mice and cause apoptosis by the formation of apoptotic bodies, nuclear condensation, activation of caspase-, decreased cell number and ascites volume, increased expression of pro-apoptotic gene, Bax, and decreased expression of anti-apoptotic gene, Bcl-. TCE could induce a reduction of papillomas, tumor yield, tumor burden, and tumor weight while increase phase II detoxifying enzymes in skin carcinoma animal models. The effect of a hydroalcoholic (% ethanol: % distilled water) extract of aerial roots of Tinospora cordifolia on Swiss albino mice revealed a significant increase in acid-soluble sulfhydryl (-SH), cytochrome P () contents, and enzyme activities of cytochrome P () reductase, cytochrome b reductase, GST, DT-diaphorase (DTD), SOD, catalase, GPX, and GR activity in the liver highlighting the chemopreventive role of Tinospora cordifolia against carcinogenicity.

In vivo anti-angiogenic activity of TCE in B-F melanoma was detected by increased levels of pro-inflammatory cytokines, including IL- β, IL-, TNF-α, granulocyte monocyte-colony stimulating factor (GM-CSF) and the vascular endothelial cell growth factor (VEGF), increased production of anti-angiogenic agents IL^- and tissue inhibitor of metalloprotease- (TIMP-) in the B-F extract-treated animals. The polysaccharide fraction from Tinospora cordifolia was found to be very effective in reducing the metastatic potential of B-F melanoma cells. Markers of neoplastic development were reduced significantly in the treated animals compared with the untreated control animals.

Most of the synthetic chemotherapeutic agents suffer from toxic side effects. The effect of Guduchi extracts was comparable or better than doxorubicin treatment.

Tinospora cordifolia: Anti-microbial activity

The methanol extracts of Tinospora cordifolia have been reported to have potential against microbial infections. The anti-bacterial activity of Tinospora cordifolia extracts has been assayed against Escherichia coli, Staphylococcus aureus, Klebsiella pneumoniae, Proteus vulgaris, Salmonella typhi, Shigella flexneri, Salmonella paratyphi, Salmonella typhimurium, Pseudomonas aeruginosa, Enterobacter aerogene, and Serratia marcesenses (Gram-positive bacteria).– In mice models, TCE has been reported to function in bacterial clearance and improved phagocytic and intracellular bactericidal capacities of neutrophils. TCE has been reported of immunostimulant properties on macrophages. Intra-mammary infusion of hydro-methanolic extracts of Tinospora cordifolia treatment showed enhanced phagocytic activity of polymorphonuclear cells in bovine subclinical mastitis.,

Tinospora cordifolia: Anti-oxidant activity

The anti-oxidant capacity of Tinospora cordifolia stem methanol extracts administered orally increased the erythrocytes membrane lipid peroxide and catalase activity. It also decreased the activities of SOD, GPx in alloxan-induced diabetic rats.,, Tinospora cordifolia Willd.(Menispermaceae) extracts possess possible inhibitors of aldose reductase and anti-oxidant agents thereby reducing chemotoxicity induced by free radicals.

TCE has been reported of its strong free radical scavenging properties against superoxide anion (O^-), hydroxyl radicals (OH), NO radical, and peroxynitrite anion (ONOO^-). The extract was also found to reduce the toxic side effects of CP in mice by the free radical formation., Tinospora cordifolialowers the levels of malondialdehyde and ROS and the higher levels of GSH and total thiols. The protective effects of Tinospora cordifolia could be observed even in the fetal milieu, with higher levels of anti-oxidant molecules and enzymes.

Tinospora cordifolia has the ability to scavenge free radicals generated during aflatoxicosis. Tinospora cordifolia showed protection against aflatoxin-induced nephrotoxicity due to the presence of alkaloids such as a choline, tinosporin, isocolumbin, palmatine, tetrahydropalmatine, and magnoflorine. A significant increase in the concentration of TBARS in brain along with a decrease in heart has been observed in diabetic rats. It also enhanced formation of SOD, GPx, and GSH in liver. Treatment with Tinospora cordifolia also inhibited glucose -phosphatase and fructose , -diphosphatase; and restored glycogen content in liver. Tinospora cordifolia has been shown to regulate blood glucose.

(R, R)-R, R-dihydroxy-S, R: , -diepoxycleroda- (), , S: ,S-dilactone (ECD), a diterpenoid from Tinospora cordifolia has been shown to possess chemo-preventive potential in DEN induced HCC rats. Treatment of ECD in both preventive and curative DEN induced animals increased the level of anti-oxidants and detoxification enzymes.

An aqueous extract of Tinospora cordifolia has a radio-protective enhancing the survival of mice against a sub-lethal dose of gamma radiation.– Tinospora cordifolia was effective in elevating the GSH levels, expression of the gamma-glutamylcysteine ligase and Cu-Zn SOD genes. Aqueous extract of Tinospora cordifolia inhibited radiation mediated -deoxyribose degradation by inhibiting the formation of (Fe⁺)-bipiridyl complex formation to confer radio-protective effects.

The arabinogalactan polysaccharide (TSP) isolated from Tinospora cordifolia showed good protection against iron-mediated lipid peroxidation of rat brain homogenate as revealed by the TBARS and lipid hydroperoxide (LOOH) assays.

Tinospora cordifolia also has the components that decrease the recurrent resistance of HIV virus to antiretroviral therapy (ART) and improve the outcome of the therapy. The effect of a hydroalcoholic (% ethanol: % distilled water) extract of aerial roots of Tinospora cordifolia on carcinogen/drug metabolizing phase-I and phase-II enzymes, anti-oxidant enzymes, GSH content, LDH and lipid peroxidation has been shown in liver of Swiss albino mice. The enhanced GSH level and enzyme activities involved in xenobiotic metabolism and maintaining anti-oxidant status of cells are suggestive of a chemo-preventive efficacy of Tinospora cordifolia.

Tinospora cordifolia has been reported to contain an alpha-glucosidase inhibitor, characterized as saponarin (apigenin--C-glucosyl--O-glucoside). The leaf extract had appreciable anti-oxidant and hydroxyl radical scavenging activities. Pepticare, a herbomineral formulation of the Ayurveda medicine consisting of the herbal drugs: Glycyrrhiza glabra, Emblica officinalis and Tinospora cordifolia, has anti-ulcer and anti-oxidant activity in rats.

Hyponidd is another herbomineral formulation composed of the extracts of  medicinal plants (Momordica charantia, Melia azadirachta, Pterocarpus marsupium, Tinospora cordifolia, Gymnema sylvestre, Enicostemma littorale, Emblica officinalis, Eugenia jambolana, Cassia auriculata and Curcuma longa). Hyponidd administration also decreased levels of glycosylated hemoglobin, plasma thiobarbituric acid reactive substances, hydroperoxides, ceruloplasmin and alpha-tocopherol in diabetic rats.

Anti-oxidant activities of Dihar, a polyherbal formulation containing drugs from eight different herbs viz., Syzygium cumini, Momordica charantia, Emblica officinalis, Gymnema sylvestre, Enicostemma littorale, Azadirachta indica, Tinospora cordifolia and Curcuma longa in streptozotocin induced type  diabetic rats. Dihar produced a significant decrease in serum creatinine and urea levels in diabetic rats.

Tinospora cordifolia: Effects on other diseases

A dose dependent reduction in infarct size and in lipid peroxide levels of serum and heart tissue were observed with the prior treatment of Tinospora cordifolia. The activation of macrophages by cytotoxic T cells leads to increase in GM-CSF which leads to leucocytosis and improved neutrophil function. Octacosanol isolated from Tinospora cordifolia inhibits proliferation of endothelial cells and Ehrlich ascites tumor cells, inhibits neovascularization induced by angiogenic factors in chick chorioallantoic membrane and rat cornea in vivo angiogenesis assays and also inhibits secretion of ascites fluid in the growing tumor cells in vivo by inhibiting activity of matrix metalloproteinases (MMPs) and translocation of transcription factor nuclear factor-kappa-B (NF-κB) to nucleus. Oral administration of % methanolic extract of Tinospora cordifolia stem reduces sperm motility and density, lowering of serum testosterone, protein, sialic acid, glycogen contents, and depletion of vesicular fructose of testes leading to reduction of male fertility in rats. The in vivo administration of alcoholic extract of Tinospora cordifolia has been reported to increase bone marrow derived macrophages (BMDM) in bearing Dalton's lymphoma (DL). The polyherbal preparations Caps HT of Tinospora cordifolia, could reduce plasma recalcification time and enhanced the release of lipoprotein lipase enzyme., Other polyherbal HP- has hepatocurative and anti-oxidant efects.

TABLE 1: PHARMACOLOGICAL ACTIVITIES REPORTED FROM TINOSPORA CORDIFOLIA

 TABLE 2: CHEMICAL CONSTITUENTS RESPONSIBLE FOR THE BIOACTIVITY: ^{7, 34, 66, 67}

 Tinospora cordifolia fruit

Tinospora crispa

Tinospora sinensis

REFERENCES:

1. Kaur R., Kaur H. The antimicrobial activity of essential oil & plant extracts of Woodfordia fruticosa. Archives of Applied Science & Research 2010; 2: 302-9.
2. Kaur R., Kumar S., Sharma AK. Medicinal plants for the treatment of sexual transmitted diseases. International Journal of Pharmaceutical Innovations 2012; 2: 13-23.
3. Meena AK., Singh A., Panda P. Tinospora cordifolia: Its bioactivities & evaluation of physicochemical properties. International Journal of Pharmacognosy & Phytochemical Reseach 2010; 2: 50-55.
4. Atal CK., Kapoor BM. Cultivation & Utilization of Medicinal Plants. 1989. (Edn: PID, CSIR)
5. Siddiqui HH. Safety of Herbal Drugs: An overview. Drugs News & Views. 1993; 1: 7-10.
6. Kaur R., Kaur H., Dhindsa AS. Glycyrrhiza glabra: A phytopharmacoloical review. International Journal of Pharmaceutical Sciences & Research 2013; 4: 2470-77.
7. Neeraja PV., Margaret E. Amruthavalli: Tinospora cordifolia: Multipurpose rejuvenator. International Journal of Pharmaceutical, Chemical & Biological Sciences 2013; 3: 233-41.
8. Raghu AV., Geeta SP., Martin G., Ravindran PN. In vitro Dev Biol Plant 2006; 42:584-8.
9. Anonymous Wealth of India: Raw materials, Vol: 10. New Delhi: CSIR 1976.
10. Kirtikar KR., Basu BD. Indian Medicinal Plants Vol.2 (Lalit Mohan basu, Leader Road, Allahabad) 1933:77.
11. Mitra R., Raghunandan K. Anonymous, Pharmacognosy of Indigenous Drugs Vol. 1; (Central Council for Research in Ayurveda & Siddha, New Delhi) 1982: 321.
12. Sharma P C., Yelne M B., Dennis T J. Data Base on Medicinal Plants Used in Ayurveda, Vol. III, (Documentation & Publication Division, Central Council for Research in Ayurveda & Siddha, New Delhi), 2001: 256.
13. Charka, Charaka Samhita, Part I & II, (Hindi commentary by Pandey & Chaturvedi), Edited by Rajeshwar Datta Shastri, (Chaukhambha Vidyabhawan, Varanasi), 1961
14. Sushruta, Sushruta Samhita, commentary by Dalhana, Edited by Jadavji Trikamji Acharya, (Chaukhambha Orientalia, Varanasi & Delhi), 1992.
15. Vaagbhata, Ashtanghridayam, Commentary by Arunadatta & Hemaadri, collected by Kunt & Narvare and Edited by Paradkara, (Chaukhambha Orientalia, Varanasi & Delhi), 1982.
16. Misra B. Bhava Prakash Nighantu, Vol. 1, (Hindi commentary by K C Chunekar), (Chowkhamba Vidya Bhavan, Varanasi), 1969: 269.
17. Aiyer K N; Kolammal M. Pharmacognosy of Ayurvedic Drugs of Kerala, (Central Research Institute Trivendrum) 1963; 1:28.
18. Watt G. A Dictionary of Economic Products of India, Vol. 6(pt 4), Reprinted edition,(Periodical Experts, Delhi) 1972: 63.
19. Pendse G P., Bhatt S K. Chemical Examination of some Indian Medicinal Plants. Tinospora cordifolia, Solanum xanthocarpum & Fumaria officinalis,Indian Journal of Medicinal Research 1932; 20: 653.
20. Singh K K., Maheshwari J K. Traditional Phytotherapy Amongst the Tribals of Varanasi Distric, U.P. Journal of Economic & Taxonomic Botany 1983; 4: 829.
21. Shah G L. Some Economically important plants of Salsette Island near Bombay. Journal of Economic & Taxonomic Botany 1984; 5: 753.
22. Bhatt R P & Sabnis S D, Contribution to the Ethnobotany of Khedbrahma region of North Gujarat. Journal of Economic & Taxonomic Botany 1987; 9: 139.
23. Anonymous, An Appraisal of Tribal-Folk Medicine, (Central Council for Research in Ayurveda & Siddha, New Delhi) 1999.
24. Vir J; Dar G H; Bhat G M, Taxo-ethnobotanical studies of the rural areas in district Rajouri (Jammu). Journal of Economic & Taxonomic Botany 1984; 5: 831.
25. Shah G L., Yadav S S., Badri N. Medicinal Plants from Dahanu Forest Division in Maharashtra State. Journal of Economic & Taxonomic Botany 1983; 5: 141.
26. The Wealth of India, Raw Materials; Publication & Information Directorate, Council of Scientific & Industrial Research: New Delhi 1982; 10: 252.
27. Singh SS., Pandey SC., Srivastava S., Gupta VS., Patro B. Chemistry & medicinl properties of Tinospora cordifolia. Indian Journal of Pharmacology 2003; 35: 83.
28. Qudrat-I-Khuda M., Khaleque A., Ray N. Scientific Research (Dacca) 1964; 1: 177.
29. Ghosal S., Vishwakarma RA. Tinocordiside: a new rearranged cadinene sesquiterpene glycoside from Tinospora cordifolia. Journal of Natural Product 1997; 60: 839.
30. Anuman JH., Amak R., Bhat R., Sabata B. Journal of Natural Product 1988; 51: 197.
31. Maurya R; Sukhdev S. Tinocordifolin: A sesquiterpene from Tinospora cordifolia. Phytochemistry 1998; 49:1343.
32. Kiem PV. Minh CV., Dat NT., Kinh LV. Fitoterapia 2010; 81: 485.
33. Joshi V., Joshi RP. Some plants used in Ayurvedic & Homoeopathic Medicine. Journal of Pharmacognosy & Phytochemistry 2013,2: 269-75.
34. Pandey M., Vyas MK., Sharma R. Tinospora cordifolia: A climbing shrub in health care management. International Journal of Pharmaceutical & Biosciences 2012; 3: 612-8.
35. Kosaraju J., Roy PD. Neuroprotective effect of Tinospora cordifolia ethanol extract on 6- hydroxydopamine induced Parkinson disease. International Journal of Pharmacology 2014; 46: 176-80.

36. Kaur M., B Kumar, A Singh. Comparative antidiarrhoel & antiulcer effect of aqueous & ethanolic extracts of Tinospora cordifolia in rats. International Journal of Pharmaceutical Technology & Research 2014; 5: 122-8.
37. Kaur M., Singh A, Kumar B. Comparative antidiarrhoel & antiulcer effect of aqueous & ethanolic extracts of Tinospora cordifolia in rats. International Journal of Pharmaceutical Technology & Research 2014; 5: 122-8.
38. Goel B., Pathak N. Clinical evaluation of analgesic activity of Guduchi, Tinospora cordifolia using animal model. Journal of Clinical Diagnosis & Research 2014; 8: 1-4.
39. Wani JA., Neema RK. Phytochemical screening & aphrodisiac activity of Tinospora cordifolia. International Journal of Pharmaceutical & Clinical Research 2011; 3: 21-26.
40. Gupta MS, Sharma GD, Chakraborty B. Effect of aqueous extract of Tinospora cordifolia on functions of peritoneal macrophages isolated from CCl4 intoxicated male albino mice. BMC Complementary & Alternate Medicine 2011; 119102
41. Kumar V., Mahdi F., Chander R, Hussain I. Tinospora cordifolia regulates lipid metabolism in alloxan induced diabetes in rats. International journal of Pharmacy & Life Sciences 2013; 4: 3010-17.

42. Ramesh V., Jayaprakash R;, Sridhar MP. Antioxidant activity of ethanol extract of Tinospora cordifolia on N-nitrosodiethylamine induced lier cancer in male wistar albino rats. Journal of Pharmaceutical & Bioallied Sciences 2015, 1: 45-50.
43. Patgiri B., Umretia BL., Prajapati PK., Shukla VJ. Anti-inflammatory activity of aqueous extract of Tinospora cordifolia. Ayurveda 2014; 35: 108-10
44. Antonisamy P., Dhanasekaran M., Balthazar JD. Gastroprotective effect of epoxy clerodane diterpene isolated from Tinospora cordifolia on indomethacin induced gastric ulcers in rats. Phytomedicine 2014; 21: 966-9.
45. Gupta A., Raj H., Upmanyu N. Evaluation of B. monnieri, cordifolia, E alsinoides & their combinations on cognitive functions in rats. Current Agriculture Sciences 2013; 6:239-43.
46. Patel A., Singh CS., Patel NS. Radioprotective & cytoprotective activity of Tinospora cordifolia stem enriched extract containing Cordifolioside. Indian Journal of Pharmacology 2013; 45: 237-43.
47. Ratnasamy R., Compos AM. A new antifeedant clerodane diterpenoid from Tinospora cordofolia. Natural Product Review 2013; 27:1431-6.
48. Gupta R., Sharma V. Ameliorative effect of Tinospora cordifolia root extract on histopathological & biochemical changes induced by aflatoxin b1 in mice kidney. Toxocol. Int. 2011; 18: 94-8.
49. Sharma AK., K Kishore K, Sharma D., Agarwal SS., Singh SK. Cardioprotective activity of alcoholic extract of Tinospora cordifolia in CaCl2 induced cardiac arrhythmia in rats. Journal of Biomedical Research 2011; 25: 280-6.
50. Stance MH., A Nagy A., Tosa M., Vlad L. Hepatoprotective effect of orally administered melatonin & Tinospora cordifolia in experimental jaundice. Chirurgia (bucur) 2011; 106(2), 205-10.
51. Patel MB., Mishra S. Hypoglycaemic activity of alkaloidal fraction of Tinospora cordifolia. Phytomedicine 2011; 18: 1045-52.
52. Jain BN., Jain VK., Shete A. Journal Advanced Pharmaceutical Technology Research 2010;1: 30-3.
53. Dhingra D., Goyel PK. Evidence for the involvement of monoaminergic & GABAergic systems in antidepressant like activity of Tinospora cordifolia in mice. Indian journal of Pharmaceutical Sciences 2008; 70: 761-7.
54. Kapoor P., Jarry H., Wuttke W. Evaluation of antiosteopotential of Tinospora cordifolia in female rats. Maturitas 2008; 59: 329-38.
55. Jagetia GC, Rao SK. Evaluation of antineoplastic activity of Guduchi, Tinospora cordifolia in Ehrlich ascites carcinoma bearing mice. Biological Pharmaceutical Bulletin. 2006; 29: 460-6.
56. Gupta RS., Sharma A. Antifertility effect of Tinospora cordifolia stem extract in male rats. Indian Journl of Experimental Biology 2003; 41: 8859-64.
57. Tiwari M., Kakkar P., Dwivedi UN. Tinospora cordifolia extract modulates COX-2, iNOS, ICAM 1, pro-inflammatory cytokines & redox status in murine model of asthma. Journal of Ethnopharmacology 2014; 28: 326-37.
58. Mishra R., Kaur G. Aqueous ethanolic extract of Tinospora cordifolia as a potential candidate for differentiation based therapy of glioblastomas. PLOS One 2013; 8.
59. Nadig PD., Dethe SM., Revankar RR., Aliyar MA. Effect of Tinospora cordifolia on experiental diabetic neuropathy. Indian Journal of Pharmacology 2012; 44: 580-3.
60. Baskar A., Agastian P., Dhanasekaran M. Chemopreventive potential of epoxy Clerodane diterpene from Tinospora cordifolia against diethylnitrosamine induced hepatocellular carcinoma. Invest New Drugs 2009; 27: 347-55.
61. Singh V., Banyal HS. Antimalarial effect of Tinospora cordifolia & Cissampelos pareira on Plasmodium berghei. Current Science 2011; 110: 1356-8.
62. Xavier TF., Anand SP. Antibacterial activity of stem extracts of Tinospora cordifolia. Ancient science Life 2003; 23: 40-3
63. Mishra R, G Kaur. Tinospora cordifolia induces differentiation & senescence pathways in neuroblastoma cells. Molecular Neurobiology 2015; 52: 719-33
64. Ashok BK., Ravishankar B., Bhat SD. Antipyretic activity of Guduchi ghrita formulations in albino rats. Ayu 2010; 31: 367-70.
65. Badar VA., Thawani VR., Wakode PT. Efficacy of Tinospora cordifolia in allergic rhinitis. Journal of Ethnopharmacology 2005; 96: 445-9
66. Sharm MM., Batra A., Mittal J. Tinospora cordifolia: A multipurpose medicinal plant- A review. Journal of Medicinal Plant Studies 2014; 2: 32-47
67. Spandana U., Ali SL., Nirmala T. A review on Tinospora cordifolia. International Journal of current Pharmaceutical review & Research 2013; 4: 61-68

 web pages

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792597/

https://www.ncbi.nlm.nih.gov/pubmed/1529024

https://en.wikipedia.org/wiki/Tinospora_cordifolia

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924974/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190733/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3987186/

http://ijpsr.com/?action=download_pdf&postid=24108

https://dx.doi.org/10.4103%2F0257-7941.107344

http://ml.indianmedicinalplants.info/index.php?title=%E0%B4%9A%E0%B4%BF%E0%B4%B1%E0%B5%8D%E0%B4%B1%E0%B4%AE%E0%B5%83%E0%B4%A4%E0%B5%8D