Tinospora

Scientific Name(s): Tinospora cordifolia (Willd.) Miers. Family: Menispermaceae (moonseeds)

Common Name(s): Guduchi , amrita (Sanskrit), giloe , gulancha (Bengali), giloya (Hindi), gado , galo (Gujarati), duyutige , teppatige (Telugu), heartleaf moonseed (English), Tinofend

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. Experiments have examined its antineoplastic, antioxidant, hepatoprotective, hypolipidemic, and immunologic properties; however, few clinical trials exist.

Dosing

Clinical trials to support dosing are limited, with 300 mg of a standardized aqueous tinospora stem extract taken 3 times daily for up to 6 months.

Contraindications

Contraindications have not been determined. An in vitro study found an increase in prostate cancer cells; therefore, tinospora probably should not be consumed in this condition until further studies are conducted.

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; GI symptoms (anorexia, nausea, vomiting) have been reported. No toxicity has been observed at Ayurvedic therapeutic doses.

Toxicology

Information is generally lacking.

Botany

T. cordifolia is a glabrous, succulent, climbing shrub native to India and also found in Burma and Sri Lanka. It thrives easily in tropical regions, often growing to great heights, and climbing the trunks of large neem trees. The bark is gray or creamy white, deeply cleft spirally and longitudinally, with large rosette-like lenticels. The wood is white, soft, and porous, and when freshly cut, quickly assumes a yellow tint. The branches bear smooth, heart-shaped leaves, unisexual greenish flowers in summer, and red berries in winter. Long thread-like aerial roots arise from the branches. The viscous sap is light yellow, with an odor and a nauseating bitter taste. 1 , 2

History

Guduchi is an Indian medicinal plant that has been used in Ayurvedic preparations for the treatment of various ailments for centuries. Ancient Hindu physicians prescribed it for gonorrhea. Europeans in India became interested in the tonic and diuretic properties of T. cordifolia . The prepared tincture has received official recognition in the Indian Pharmacopoeia . 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, roots, and whole plant of T. cordifolia , and reviews describing the constituents have been published. 5 , 6

Major constituents include the alkaloids berberine, tinospporin, palmitine, tembetarine, choline, isocolumbin, and tetrahydropalmatine; the steroids sitosterol, octacosanol, heptacosanol, nonacosan-15-one, hydroxyecdysone, makisterone, giloinsterol, diterpenoid lactones, furanolactones, tinosporon, and columbin; and the glycosides 18-nonderodane glycoside, furanoid diterpene glycosides, tinocordifoliside, tinocordiside, cordiside, cordifoliside, plamatosides, and syringin. 5 , 6 , 7 , 8 , 9

Uses and Pharmacology

Antineoplastic effects
Animal data

Tumor mass reduction and increased survival time have been observed with administration of the extract in several experiments in mice with implanted carcinomas. 10 , 11 In similar experiments, tinospora extracts restored thymus homeostasis, retarded tumor growth, and prolonged survival times. 12 , 13 , 14 , 15 Tinospora extract showed a regulatory effect on serum cytokine, with consequent angiogenesis inhibition of mouse melanoma cells. 16

Survival time was increased after irradiation, and body weight loss was decreased in mice pretreated with a single dose of tinospora extract. 17 , 18 Pretreatment with stem and root extracts was also protective of the spleen and testis in rodents, 19 , 20 while conversely, HeLa cells showed an increased radiosensitivity with a dichloromethane stem extract. 21

A dose-dependent cytotoxic effect of tinospora extract in HeLa-cultured cells comparable with doxorubicin has been reported. 22 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. 23 In vitro studies suggest T. cordifolia may contain compounds that act via the androgen receptor and cause an increase in proliferation of prostate cancer cells. 24

Clinical data

Research reveals no clinical data regarding the use of tinospora for use in the treatment of cancers. Because of proneoplastic potential demonstrated in some experiments, 21 , 23 , 24 caution is warranted.

Antidiabetic and hypolipidemic effects
Animal data

Aqueous and ethanol extracts of T. cordifolia leaf, root, and stem administered to alloxan-induced diabetic rats caused a dose-dependent reduction in blood glucose levels similar to glibenclamide and insulin. 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 In similar experiments, serum and tissue cholesterol, phospholipid, and free fatty acid levels were reduced. 5 , 6 , 26 , 34

Clinical data

Research reveals no clinical data regarding the use of tinospora for treating diabetes.

Antioxidant effects

In vitro studies have demonstrated inhibition of lipid peroxidation, inhibition of nitric oxide synthase activity, and direct nitric oxide–free radical scavenging, as well as generation of superoxide and hydroxyl radicals. 23 , 35 , 36 , 37 , 38

Animal data

Markers of oxidative stress were reduced in rodents with induced diabetes, hepatotoxicity, and renal toxicity in several studies. 15 , 26 , 30 , 31 , 39 , 40 , 41 , 42

Clinical data

Clinical studies have been conducted to evaluate the hepatoprotective effect of T. cordifolia extracts on isoniazid- and rifampicin-induced oxidative stress in patients with tuberculosis. One large study used a combination of tinospora with curcumin; therefore, the positive results cannot be attributed to either plant individually. 43 A second clinical trial evaluated tinospora alone and in combination with Phyllanthus emblica . In that trial, tinospora alone was no more effective than placebo. 44

Immunologic effects

T. cordifolia is widely used in the Indian Ayurvedic system of medicine as an immunostimulant. 45 Syringin, cordiol, cordioside, and cordifoliosides A and B are the active principles responsible for anticomplement and immunomodulatory activities, 46 , 47 as well as an arabinogalactan polysaccharide isolated from the dried stems and an alpha-D-glucan. 3 , 45 , 48 , 49

Animal data

Studies in rats have shown modulation of the immune response to stress via cytokines, and inhibition of stress-induced gastric ulceration and hypothermia has also been demonstrated in rats. 50 , 51 , 52 , 53 A protective effect of tinospora against cyclophosphamide-induced urotoxicity was attributed to modulation of cytokines and glutathione. 42 Gunduchi fed to cows peripartum resulted in increased milk production, increased immune markers in the cow, and increased plasma growth hormone. 54 Cows with mastitis showed an increase in the phagocytic immune response when fed tinospora. 55

Clinical data

An aqueous extract of T. cordifolia reduced allergic rhinitis, sneezing, nasal obstruction, and pruritus in a randomized clinical trial over 8 weeks. 56 A clinical trial evaluated the effect of tinospora on diabetic foot ulcers as adjuvant therapy. A decrease in the number of debridements was observed, related to increased phagocytic function. However, measures of net improvement did not favor tinospora use. 57 A decrease in reported symptoms was found in a clinical trial of tinospora in HIV patients. No differences were found in CD4 counts, and unexplained hematological measures were noted. 58 , 59 A clinical study compared a polyherb formulation containing tinospora with hydroxychloroquine sulfate in rheumatoid arthritis. However, the effectiveness cannot be attributed to any one of the several plants in the preparation. 60 Older studies suggested T. cordifolia strengthened host defenses and improved the surgical outcome in patients with extrahepatic obstructive jaundice. 61 , 62 , 63

Other effects
CNS

In a tail suspension and forced swim test, tinospora showed antidepressant activity, possibly via inhibition of monoamine oxidase activity. 64

Osteoporosis

Limited studies in rats by 1 group of researchers suggest an antiporotic effect of stem extract and beta-ecdysone on bone density, considered to be acting via a mechanism independent of estrogen receptors. 65 , 66 , 67

Other reported properties of the plant include a decreased infarction size in rats 68 and hepatoprotection with a return to healthy levels of ALT, AST, serum alkaline phosphatase, and serum bilirubin in carbon tetrachloride–injured rats. 69 , 70 , 71 Gunduchi fed to cows peripartum resulted in increased milk production but with no effect on composition. 54

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 daily for 8 weeks. 56 Similarly, a clinical study in HIV patients used 300 mg of a standardized aqueous tinospora stem extract 3 times daily for 6 months. 58

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 cytochrome P450 enzymes. 23

Adverse Reactions

Few adverse reactions were reported in limited clinical trials. 56 , 58

Toxicology

Information is generally lacking about the toxicology of T. cordifolia in humans. At Ayurvedic therapeutic doses, no toxicity has been observed. 5 No adverse events were observed in healthy volunteers given 500 mg/day for 21 days. 72 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 71 , 73 and in rats at doses of 1,000 mg/kg of the whole plant extract. 68 However, 40% mortality resulted after mice were given 500 mg/kg body weight of an extract of tinospora stems. 17 Genotoxicity tests in rats given up to 250 mg/kg body weight for 7 days showed no clastogenicity or DNA damage, and T. cordifolia was not mutagenic in Salmonella typhimurium strains. 74 However, hydroalcoholic extracts did promote micronuclei formation in bone marrow cells. 5

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