Tinospora
Tinospora cordifolia (Willd.) Miers. Family: Menispermaceae (moonseeds)
Guduchi , amrita (Sanskrit), giloe , gulancha (Bengali), giloya (Hindi), gado , galo (Gujarati), duyutige , teppatige (Telugu), heartleaf moonseed (English)
 
Clinical Overview
Uses
T. cordifolia is used in the Indian Ayurvedic system of medicine for the treatment of jaundice, diabetes, and rheumatoid arthritis, and is also used as an immunostimulant. Limited studies have examined its antineoplastic, antioxidant, hepatoprotective, hypolipidemic, and immunologic properties.

Dosing
Few clinical trials are available to support dosing. In examining the efficacy of Tinospora in allergic rhinitis, 300 mg of an aqueous extract was given 3 times daily for 8 weeks.

Contraindications
Contraindications have not been determined.

Pregnancy/Lactation
Information regarding safety and efficacy during pregnancy and lactation is lacking.

Interactions
None well documented.

Adverse Reactions
Limited clinical studies reveal few adverse reactions.

Toxicology
Little is known about the toxicology of T. cordifolia .

 
Botany
T. cordifolia is a glabrous, succulent, climbing shrub native to India. It is also found in Burma and Sri Lanka. It thrives easily in the tropical region, often attains a great height, and climbs up the trunks of large neem trees. The bark is gray or creamy-white, deeply cleft spirally and longitudinally, with the space between spotted with large rosette-like lenticels. The wood is white, soft, and porous, and the freshly cut surface quickly assumes a yellow tint when exposed to air. The branches bear smooth heart-shaped leaves, unisexual greenish flowers in summer, and red berries in winter. Long thread-like aerial roots come up from the branches. The viscous sap is light yellow and has an odor and a nauseating bitter taste. 1,  , 2
 
History
Guduchi is an Indian medicinal plant and has been used in Ayurvedic preparations for the treatment of various ailments throughout the centuries. Ancient Hindu physicians prescribed it for gonorrhea. European medical men in India became interested in the tonic and diuretic properties of T. cordifolia . Today, the drug and a tincture prepared from it have received official recognition in the Indian Pharmacopoeia . 1,  , 3,  It has been used to treat general weakness, fever, dyspepsia, dysentery, gonorrhea, secondary syphilis, urinary diseases, impotency, gout, viral hepatitis, skin diseases, and anemia. In compound formulations, guduchi is used clinically to treat jaundice, rheumatoid arthritis, and diabetes. The root is considered to be a strong emetic and is used for bowel obstruction. 1,  , 3,  , 4
 
Chemistry
A large number of compounds have been isolated from the aerial parts and roots of T. cordifolia . In the early 1900s, giloin, gilenin, and gilosterol, as well as the bitter principles columbin, chasmanthin, and palmarin, were identified in the plant. 1,  A wide variety of sesquiterpenes and diterpenes have been isolated from the stems of the plant. The major isolated compounds include the norditerpene furan glycosides cordiofolisides A, B, and C 5,  ; the daucane-type sesquiterpenes tinocordifolin and tinocordifolioside 6,  , 7,  ; the furanoid diterpene glucosides palmatosides C and F, and amritosides 8,  , 9,  ; the clerodane diterpenoids cordioside, tinosponone, and tinocordioside 10,  , 11,  ; tinosporaside, a novel 18-norclerodane diterpene glucoside, 12,  and tinocordiside, a cadinane sesquiterpene glycoside. 13,  In addition, syringin, cordiol, cordioside, and the phenylpropene disaccharides cordifoliosides A and B were identified as the active principles with anticomplement and immunomodulatory activities. 14,  , 15,  The stems of the plant contain the alkaloid berberine. Cultures of the stem callus have the capability of synthesizing this compound. 16,  , 17,  Ecdysterone, makisterone A, and 20 beta-hydroxyecdysone are phytoecdysones isolated from the aerial parts of the plant. 18,  , 19,  , 20
Other constituents reported from T. cordifolia include a phenolic lignan, octacosanol, nonacosan-15-one, heptacosanol, beta-sitosterol, tinosporidine, cordifol, cordifolone, 21,  , 22,  magnoflorine, tembetarine, 23,  syringine and syringine apiosylglycoside, 24,  and a glucan polysaccaride. 25
The roots of T. cordifolia contain isocolumbin, palmatine, tetrahydropalmatine, magnoflorine, and jatrorrhizine. 26,  , 27
 
Uses and Pharmacology
Antineoplastic effects   Tinospora plant extracts made with water, ethanol/methanol, or methylene chloride extracts have been evaluated for antineoplastic effects in various animal experiments.
A dose-dependent cytotoxic effect of Tinospora extract in HeLa-cultured cells comparable with doxorubicin has been reported. 34,  , 35
Tumor mass reduction and increased survival time have been observed with administration of the extract in several experiments in mice with induced carcinomas. 36,  , 37,  Tinospora extract showed a regulatory effect on serum cytokine, with consequent angiogenesis inhibition in mice melanoma cells. 38
Survival time was increased after irradiation, and body weight loss was decreased in mice pretreated with a single dose of Tinospora extract. 39,  , 40
At low doses, an ethanol extract of Tinospora increased bone marrow cell counts, while higher doses resulted in decreased counts in mice with induced lymphoma. 41,  In similar experiments, Tinospora extracts restored thymus homeostasis, retarded tumor growth, and prolonged survival times. 42,  , 43,  , 44
Clinical data   No clinical trials in cancer have been published.
Antidiabetic and hypolipidemic effects   Aqueous and ethanol extracts of T. cordifolia root administered to alloxan-induced diabetic rats caused a dose-dependent reduction in blood glucose levels, similar to glibenclamide and insulin. 45,  , 46,  , 47,  , 48
In similar experiments, serum and tissue cholesterol, phospholipid, and free fatty acid levels were reduced. 46,  , 49
Clinical data   No clinical trials have been published to date.
Antioxidant effects   The antioxidant properties of T. cordifolia roots were studied by administering the aqueous extract to alloxan-induced diabetic rats. After 6 weeks, the levels of the plasma thiobarbituric acid-reactive substances ceruloplasmin and alpha-tocopherol were reduced, while the levels of glutathione and vitamin C were increased. The root extract at a dose of 5 g/kg was the most effective. 46,  In other in vitro studies, guduchi extract inhibited lipid peroxidation and generation of superoxide and hydroxyl radicals. 41,  , 50
In experiments with rat hippocampal slices, extracts of T. cordifolia demonstrated antioxidant effects such as inhibition of nitric oxide synthase activity and direct nitric oxide-free radical scavenging. 51,  , 52
Clinical data   No clinical trials have been published to date.
Immunologic effects   T. cordifolia is widely used in the Indian Ayurvedic system of medicine as an immunostimulant. 25,  Syringin, cordiol, cordioside, and cordifoliosides A and B are considered the active principles responsible for anticomplement and immunomodulatory activities. 14,  , 28 An arabinogalactan polysaccharide isolated from the dried stems of T. cordifolia showed polyclonal mitogenic activity against B-cells. 3,  An aqueous extract of the aerial parts of the plant containing an alpha-D-glucan was demonstrated to increase the activation of natural killer cells and exert a dose-dependent effect on the production of cytokines. 25,  , 29
Clinical data   An aqueous extract of T. cordifolia reduced allergic rhinitis, sneezing, nasal obstruction, and pruritus in a randomized clinical trial over 8 weeks. 30
T. cordifolia was suggested to strengthen host defenses and improve the surgical outcome in patients with extrahepatic obstructive jaundice. 31,  , 32,  , 33
Other effects   Other reported properties of the plant include a decreased infarct size in rats 53,  and hepatoprotection with a return to normal levels of ALT, AST, serum alkaline phosphatase, and serum bilirubin in carbon tetrachloride-injured rats. 54,  , 55
 
Administration & Dosage
Few clinical trials are available to determine dosing. In examining the efficacy of Tinospora in allergic rhinitis, 300 mg of an aqueous extract was given 3 times a day for 8 weeks. 30
 
Pregnancy/Lactation
Information regarding safety and efficacy during pregnancy and lactation is lacking.
 
Interactions
In an experiment in mice, an extract of the aerial parts of T. cordifolia increased the activity of some CYP-450 enzymes. 41
 
Adverse Reactions
Few adverse reactions were reported in limited clinical trials. 30
 
Toxicology
There is little known about the toxicology of T. cordifolia in humans. No adverse reactions were noted when T. cordifolia stem extract was administered to rabbits up to the highest oral doses of 1.6 g/kg, 34,  , 56,  and in rats at doses of 1,000 mg/kg of the whole plant extract. 53,  However, a 40% mortality resulted after mice were given 500 mg/kg body weight of an extract of the stems of Tinospora. 39
 
References
 

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4. Gupta SS , Verma SC , Garg VP , Rai M , et al. Anti-diabetic effects of Tinospora cordifolia . Effect on fasting blood sugar level, glucose tolerance and adrenaline induced hyperglycaemia. Indian J Med Res . 1967;55:733-745.  PubMed

 

5. Gangan VD , Pradhan P , Sipahimalani AT , Banerji A . Cordifolisides A, B, C: norditerpene furan glycosides from Tinospora cordifolia . Phytochemistry . 1994;37:781-786.  PubMed

 

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8. Gangan V , et al. Palmatosides C, F: diterpene furan glucosides from Phytochemistry -structural elucidation by 2D NMR spectroscopy. Indian J Chem, Sect B: Org Chem Incl Med Chem . 1996;35B:630-634.

 

9. Maurya R , Manhas LR , Gupta P , Mishra PK , Singh G , Yadav PP . Amritosides A, B, C and D: clerodane furano diterpene glucosides from Tinospora cordifolia . Phytochemistry . 2004;65:2051-2055.  PubMed

 

10. Maurya R , et al. Clerodane diterpenoids from Tinospora cordifolia . Phytochemistry . 1995;38:559-561.

 

11. Wazir V , et al. Cordioside, a clerodane furano diterpene glucoside from Tinospora cordifolia . Phytochemistry . 1995;38:447-449.

 

12. Khan M , et al. Tinosporaside, an 18-norclerodane glucoside from Tinospora cordifolia . Phytochemistry . 1988;28:273-275.  PubMed

 

13. Ghosal S , et al. Tinocordiside, a new rearranged cadinane sesquiterpene glycoside from Tinospora cordifolia . J Nat Prod . 1997;60:839-841.

 

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16. Padhya M , et al. Biosynthesis of isoquinoline alkaloid berberine in tissue cultures of Tinospora cordifolia . Indian Drugs . 1986;24:47-48.

 

17. Roja G , Bhangale AS , Juvekar AR , Eapen S , D'Souza SF . Enhanced production of the polysaccharide arabinogalactan using immobilized cultures of Tinospora cordifolia by elicitation and in situ adsorption. Biotechnol Prog . 2005;21:1688-1691.  PubMed

 

18. Pradhan P , et al. Two phytoecdysones from Tinospora cordifolia : structural assignments by 2D NMR spectroscopy. Indian J Chem, Sect B: Org Chem Incl Med Chem . 1997;36B:958-962.

 

19. Gangan V , et al. Phytoecdysones from Tinospora cordifolia : structural elucidation of ecdysterone and makisterone A by 2D NMR spectroscopy. Indian J Chem, Sect B: Org Chem Incl Med Chem . 1997;36B:787-792.

 

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21. Hanuman J , et al. A natural phenolic lignan from Tinospora cordifolia Miers. J Chem Soc, Perkin Trans . 1986;7:1181-1185.

 

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27. Sarma D , Khosa RL , Sahai M . Isolation of jatrorrhizine from Tinospora cordifolia roots. Planta Med . 1995;61:98-99.  PubMed

 

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31. Thatte U , Rao SG , Dahanukar SA . Tinospora cordifolia induces colony stimulating activity in serum. J Postgrad Med . 1994;40:202-203.  PubMed

 

32. Thatte U , Kulkarni MR , Dahanukar SA . Immunotherapeutic modification of Escherichia coli peritonitis and bacteremia by Tinospora cordifolia . J Postgrad Med . 1992;38:13-15.  PubMed

 

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34. Jagetia G , Nayak V , Vidyasagar MS . Evaluation of the antineoplastic activity of guduchi ( Tinospora cordifolia ) in cultured HeLa cells. Cancer Letters . 1998;127:71-82.  PubMed

 

35. Jagetia GC , Rao SK . Evaluation of cytotoxic effects of dichloromethane extract of guduchi ( Tinospora cordifolia Miers ex Hook F & THOMS) on cultured hela cells. Evid Based Complement Alternat Med . 2006;3:267-272.  PubMed

 

36. Leyon PV , Kuttan G . Inhibitory effect of a polysaccharide from Tinospora cordifolia on experimental metastasis. J Ethnopharmacol . 2004;90:233-237.  PubMed

 

37. Jagetia GC , Rao SK . Evaluation of the antineoplastic activity of guduchi ( Tinospora cordifolia ) in Ehrlich ascites carcinoma bearing mice. Biol Pharm Bull . 2006;29:460-466.  PubMed

 

38. Leyon PV , Kuttan G . Effect of Tinospora cordifolia on the cytokine profile of angiogenesis-induced animals. Int Immunopharmacol . 2004;4:1569-1575.  PubMed

 

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40. Pahadiya S , Sharma J . Alteration of lethal effects of gamma rays in Swiss albino mice by Tinospora cordifolia . Phytother Res . 2003;17:552-554.  PubMed

 

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42. Singh N , Singh SM , Shrivastava P . Restoration of thymic homeostasis in a tumor-bearing host by in vivo administration of medicinal herb Tinospora cordifolia . Immunopharmacol Immunotoxicol . 2005;27:585-599.  PubMed

 

43. Singh N , Singh SM , Shrivastava P . Effect of Tinospora cordifolia on the antitumor activity of tumor-associated macrophages-derived dendritic cells. Immunopharmacol Immunotoxicol . 2005;27:1-14.

 

44. Singh N , Singh SM , Shrivastava P . Immunomodulatory and antitumor actions of medicinal plant Tinospora cordifolia are mediated through activation of tumor-associated macrophages. Immunopharmacol Immunotoxicol . 2004;26:145-162.

 

45. Stanely P , Prince M , Prince M , Menon VP . Hypoglycaemic and other related actions of Tinospora cordifolia roots in alloxan-induced diabetic rats. J Ethnopharmacol . 2000;70:9-15.  PubMed

 

46. Stanely Mainzen Prince P , Menon VP . Hypoglycaemic and hypolipidaemic action of alcohol extract of Tinospora cordifolia roots in chemical induced diabetes in rats. Phytother Res . 2003;17:410-413.  PubMed

 

47. Prince PS , Padmanabhan M , Menon VP . Restoration of antioxidant defence by ethanolic Tinospora cordifolia root extract in alloxan-induced diabetic liver and kidney. Phytother Res . 2004;18:785-787.  PubMed

 

48. Wadood N , Wadood A , Shah SA . Effect of Tinospora cordifolia on blood glucose and total lipid levels of normal and alloxan-diabetic rabbits. Planta Med . 1992;58:131-136.  PubMed

 

49. Mainzen Prince P , Menon VP , Gunasekaran G . Hypolipidaemic action of Tinospora cordifolia roots in alloxan diabetic rats. J Ethnopharmacol . 1999;64:53-57.

 

50. Mathew S , Kuttan G . Antioxidant activity of Tinospora cordifolia and its usefulness in the amelioration of cyclophosphamide induced toxicity. J Exp Clin Cancer Res . 1997;16:407-411.  PubMed

 

51. Rawal A , Muddeshwar M , Biswas S . Effect of Rubia cordifolia , Fagonia cretica linn, and Tinospora cordifolia on free radical generation and lipid peroxidation during oxygen-glucose deprivation in rat hippocampal slices. Biochem Biophys Res Commun . 2004;324:588-596.  PubMed

 

52. Rawal AK , Muddeshwar MG , Biswas SK . Rubia cordifolia , Fagonia cretica linn and Tinospora cordifolia exert neuroprotection by modulating the antioxidant system in rat hippocampal slices subjected to oxygen glucose deprivation. BMC Complement Altern Med . 2004;4:11.  PubMed

 

53. Rao PR , Kumar VK , Viswanath RK , Subbaraju GV . Cardioprotective activity of alcoholic extract of Tinospora cordifolia in ischemia-reperfusion induced myocardial infarction in rats. Biol Pharm Bull . 2005;28:2319-2322.  PubMed

 

54. Nagarkatti D , Rege NN , Desai NK , Dahanukar SA . Modulation of Kupffer cell activity by Tinospora cordifolia in liver damage. J Postgrad Med . 1994;40:65-67.  PubMed

 

55. Bishayi B , Roychowdhury S , Ghosh S , Sengupta M . Hepatoprotective and immunomodulatory properties of Tinospora cordifolia in CCl4 intoxicated mature albino rats. J Toxicol Sci . 2002;27:139-146.  PubMed

 

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