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Review On Tinospora Cordifolia

By: Pharma Tips | Views: 8123 | Date: 02-Jul-2010

Biological source: It’s a large climbing shrub known as a Tinospora cordifolia Linn.Other species of Tinospora are: Tinospora sinensis (Lour) Merrill. It is also called as padm or kandguduchi.


Review On Tinospora Cordifolia



Tinospora Cordifolia


1.
INTRODUCTION

Biological source: It’s a large climbing shrub known as a Tinospora cordifolia Linn.

Other species of Tinospora are: Tinospora sinensis (Lour) Merrill. It is also called as padm or kandguduchi. Its leaves are big and trifoliate; Tinospora crispa (Linn.) Miers. Its action is antipyretic; Tinospora malabarica grows up to 1300m.

Family: Menispermaceae

Sanskrit name: Guduchi, Amrita, Madhuparni, Kundlini

Hindi name: Giloy

English name: Tinospora

Common Names:
Galonovelo (Gujarati), Amrutoballi, Madhuparne, Uganiballi, Amrita balli. (Kanada); Amrita, Gilo(Kashmiri), Gulancha, Gurcha (Kumaon), Amrytu, Peyamrytam, Sittamrytu Chittamritam, Chittamrutu (Malayalam), Foon kan thang (Malaya), Ambarvel, Gharol, giroli, Gulavela, Gulaveli, Guloe, Gulvel (Marathi), Harajora, Harajuri, Harjora (Mundari); Guluchi, Gulochi (Oriya); Batindu, Garham, Ga (Punjabi); rum, Gilo, Gilogularich, Zakhmihaiyat, Amridavalli, Amudam, Asasi Kaippuchindil, Kunali, Narsindil, Niraidarudian, Paganrai, Padalamulam, Parivai, Pattigai, Sadi, Sagadundam, Sagamuli, Silam, Sindil, Sivandi, Sivedai, Ubavam, Vallikkandam, Vayamadu (Tamil); Duyutige, Guduchi, Iruluchi, Jivantik, Madhuka, Manapala, Somida, Tellatippatige, Tippatige (Telugu).

Distribution: Gaduchi is a climber found throughout the tropical regions of India. In Himachal Pradesh, it is easily found as a robust climber mainly in areas like Una, Paonta, Hamirpur, and Kangra etc. It climbs over the highest trees and throws out aerial roots which reach the length of 30 feet. It grows up to the height of 1000 feet in India.

Cultivation:
Manures, fertilizers and pesticides: The medicinal plants have to be grown without chemical fertilizers and use of pesticides. Organic manures like, Farm Yard Manure (FYM), Vermi-Compost, Green Manure etc. may be used as per requirement of the species. To prevent diseases, bio-pesticides may be used.
Irrigation: The field after plantation should be irrigated periodically as and when required at weekly or fortnightly intervals. Harvesting/post-harvesting operation: Mature plants are collected, cut into small pieces and dried in shade.

Cultivation method: The plant is sometimes cultivated for ornamental value and is propagated by cuttings. It is so easy to propagate that even if a twig of it is placed on a branch of a tree, it will establish itself as a giant chamber in a couple of years.

Yield: Approximately 8-10 quintal/ha. A complete package on cultivation technology of Tinospora cordifolia has been developed at Regional Research Laboratory Canal Road, Jammu.

Morphology: Tinospora is a glabrous, climbing shrub with corky grey dotted bark. It is a perennial deciduous twiner with succulent stem and papery bark. The leaves are 10-20cm in diameter, broadly ovate, deeply cordate and shortly acuminate. The flowers are small and greenish yellow on the old wood in 7.5-15 cm long racemes; slender, usually solitary in the female and clustered in male. Fruits are red in colour and similar to shape of pea.
 

Flowering/Fruiting season: March-June/cold season

Chemical Constituent:
Major constituents Sesquiterpene tinocordifolin, Sesquiterpene glucoside tinocordifolioside, tinosponone, tinocordioside, cordioside, furanoid diterpine; a new clerodane furano-diterpene viz. columbin, tinosporaside5; an immunologically active arabinogalactan; two phytoecdysones viz., ecdysterone and makisterone and several glycosides isolated as polyacetates and others are Alkaloidsll.12 viz., jatrorrhizine, palmatine, Berberine, tembeterine; phenyl propene disaccharides cordifolioside A, Band C2.10; choline, tinosporic acid, tinosporal, tinosporon, 20-fJ-hydroxyecdysoneI3, palmatosides C and F14, cordifolisiqes D and E15, diterpenoid furanolactonesl6.

 H3CO2C       OR2
1: R1=H, R2= β-D-Glucopyranosyl; Amritoside A
1a: R1 =Ac, R2=Tetra-O-acetyl-β-D-Glucopyranosyl, Amritoside A pent acetate

3: R1=H, R2= β-D-Glucopyranosyl, Amritoside C
3a: R1=Ac, R2=Tetra-O-acetyl-β-D-Glucopyranosyl, Amritoside C pent acetate

OR
4: R=β-D-Glucopyranosyl, Amritoside D
4a: R=Tetra-O-acetyl-β-D-Glucopyranosyl, Amritoside D tetra acetate

Apigenin (a flavonoid)
Traditional 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. It is an alterative, anthelmintic, anti pyretic, aphrodisiac, bitter tonic, and blood purifier, cardiac, carminative digestive, diuretic and expectorant. The starch from the roots and stem is used in chronic diarrhoea and dysentery. The juice of fresh plant is diuretic and used in gonorrhoea. Very few studies have examined its anti neoplastic, antioxidant, hepatoprotective, hypolipidemic, and immunologic properties.

The root, stem, leaves and sattva (starch) of tinospora are used for medicinal purpose, externally; the medicated oil of the plant is effectively used to relieve pain and edemas, in gout and skin disorders. In filariasis, the paste of Guduchi, shunthi, devadara and vidanga works when applied externally.

Internally, tinospora is one of the most effective Rasayanas – rejuvenatives. It works excellently on all the seven dhatus and keeps the body system in balance. The Rasayanas property bestows longevity, enhances memory, and improves general health, better complexion, energy and luster of the skin. 

In vata doshas diseases, it is given with ghrita, pitta doshas diseases, it is given with sugar, kapha doshas diseases, it is given with honey.

It is massively helpful in the digestive ailments like hyperacidity, colitis, worm infestations and loss of appetite, abdominal pain, excessive thirst, emesis and liver disorders like hepatitis.

It is one of the best tonics used in chronic fevers in the form of guduchi swaras 
(Juice). It alleviates burning sensation, thirst and increases the appetite of the     patient.

In urinary tract problems, the fresh juice of Guduchi (10-20 gms) and paashan bhed (2 gms) along with one table spoon honey mixed together given three to four times a day is effective.

Guduchi is drug of choice amongst all the remedies in treating gout (vatarakta). The decoction of Guduchi and sunthi is a very effective combination for the treatment of gout and rheumatic disorders. The juice of Guduchi is helpful for gout if taken for a period of two to three months. Also purified shilajit with juice of Guduchi is helpful for gout if taken twice daily.

leaves and roots is used to treat fever, cholera, diabetes, rheumatism and snake-bites, an infusion of the stem is drunk as a vermifuge, a decoction of the stem is used for washing sore eyes and syphilitic sores, the crushed leaves are applied on wounds and made into poultice for itch. Also it reduces thirst, internal inflammation, and increases appetite.

In general folklore, the stem decoction is considered antipyretic, useful as an antimalarial and a wash for skin ulcers. Traditionally an infusion is used to treat fever due to malaria and also in cases of jaundice and for use against intestinal worms.

It is also an effective remedy in the treatment of tropical ulcers. In powder form, it is prescribed in fevers. A preparation with coconut oil is an effective cure for rheumatism and also for flatulence of children (kabag) [Quisumbing]. A decoction of the fresh root mixed with pepper and goat’s milk is given for rheumatism, where the dose is half a pint (in doses of two to four ounces according to another author under chronic rheumatism and syphilitic cachexia) every morning.

Roots rubbed with bonduc nuts in water are given for stomachache, especially in children [Nadkarni]. Indonesians use an infusion of the stems to treat fevers and malaria. They can also be used to treat stomachache and jaundice. The infusion is also useful in fevers caused by smallpox and cholera.

The results showed that the antihyperglycaemic effect is not due to interference with intestinal glucose uptake or uptake of the sugar into the peripheral cells and that the antihyperglycaemic effect of T. crispa is probably due to stimulation of insulin release via modulation of beta-cell Ca2+ concentration. That the insulin tropic effect of T. crispa is physiological suggests that the extract contains compounds which could be purified for use in the treatment of type II Diabetes.

The cycloeucalenol and cycloeucalenone present in the stems produced mild cardiotonic effects.

Dosage: Decoction 50 – 100 ml, churna 3 -6 gm, satva 1 – 2 gm.

2. REVIEW OF LITERATURE

1. Pharmacological review

Pahadiya S et al14 has evaluated the radioprotective effect of an aqueous extract of Tinospora cordifolia (TC) against Co(60) gamma radiation in the dose of 5 mg/kg body wt to Swiss albino mice. It has shown  significant protection in terms of survival percentage. 

Grover JK et al15  has evaluated the extract of M. charantia (200 mg/kg), E. jambolana (200 mg/kg), M. pruriens (200 mg/kg) and T. cordifolia (400 mg/kg) was administered for 50 days in STZ induced diabetic mice, the plasma glucose concentration was reduced by 24.4, 20.84, 7.45 and 9.07% respectively. 

Mary NK et al16has evaluated T. cordifolia as antioxidant, anticoagulant, platelet antiaggregatory, lipoprotein lipase releasing, anti-inflammatory and hypolipidaemic activity in rats in the dose of 5 mg/kg. The extract has significantly (p<0.001)  enhanced release of lipoprotein lipase enzyme. 

Gupta R. S. et al17 Oral administration of 70% methanolic extract of T. cordifolia stem to male rats at the dose level of 100 mg/rat/day for 60 days did not cause body weight loss but decreased the weight of testes, epididymis, seminal vesicle and ventral prostate in a significant manner. The stem extract brought about an interference with spermatogenesis. These results suggested antifertility effects of the stem extract of T. cordifolia in male rats.

Umamaheswari S. et al 18 has evaluated the antihyperglycemic effect of 'Ilogen-Excel' in streptozotocin induced diabetic rats in the dose of 50 mg/kg and 100 mg/kg .It has shown significantly lowered levels of blood glucose and significantly increased levels of plasma insulin, hepatic glycogen and total hemoglobin. 

Grover JK et al19 has evaluated Tinospora cordifolia (TC) are used as a household remedy for diabetes in the dose of 21-120 days. It has found that extract has shown percent reduction in glucose decreased significantly in the moderate and severe diabetes; 55.62 and 17.72% for EJ and 48.81 and 0% for TC at the similar time intervals.
 
Mathew S et al20 has evaluate  reducing the chemotoxicity induced by free radical forming chemicals in the dose of 25 mg/kg b.wt, 10 days in mice. It has found
extract of Tinospora cordifolia has been shown to inhibit the lipid peroxidation and superoxide and hydroxyl radicals in vitro. 

Singh SM et al21 has evaluate influence of T. cordifolia on myeloid differentiation of bone marrow progenitor cells and the recruitment of macrophages in response to tumor growth in situ. It has found extract of Tinospora cordifolia can influence the myeloid differentiation of bone marrow progenitor cells and the recruitment of macrophase in response to tumor growth in situ.

 Thatte UM  et al22 has evaluate  the protective effects of Asparagus racemosus (AR) and Tinospora cordifolia (TC) against myelosuppression induced by single doses of cyclophosphamide (CP) 200 mg/kg. It has found that extract of Tinospora cordifolia is potent immunostimulant, with effects comparable to lithium and glucan. 

Chaudhary R et al23 Tinospora cordifolia (Guduchi), an Indian medicinal plant, was used to explore antitumor promoting activity in a two-stage skin carcinogenesis model at 100 mg/kg body weight/day for 16 weeks. It has been observed that cumulative number of papillomas, tumor yield, tumor burden, and tumor weight showed significant reduction along with significant elevation of phase II detoxifying enzymes, and inhibition of lipid peroxidation in liver and skin in the animals administered with such plant extract concomitant to carcinogen exposure.

Kar A et al24 has evaluate hypoglycaemic activities of the experimental herbal samples in the dose of 250 mg/kg . It has found that extract of Tinospora cordifolia shows the blood glucose lowering effect within 2 weeks in alloxan diabetic albino rats. 

Nemmani KV  et al25 has evaluate cell proliferation and natural killer cell activity by polyherbal formulation, Immu-21containing Ocimum sanctum, Withania somnifera, Emblica officinalis and Tinospora cordifolia in mice in the dose of 30 mg/kg once a day for 14 and 21 days. The results indicate that pretreatment with Immu-21 selectively increased the profileration of splenic leukocyte to B cell mitogen, Lipopolysaccharide (LPS), and cytotoxic activity against K 562 cells in mice.

Rao PR et al26 It has been suggested that the beneficial effects of reperfusing the myocardium might be in part reversed by the occurrence of reperfusion injury. Oxidative stress was suggested to be implicating in the pathogenesis of ischemia-reperfusion (I/R) injury. Many antioxidative plants were shown to be cardioprotective in experimental models of myocardial ischemia-reperfusion (I/R) injury. The present study was designed to investigate the effects of pretreatment with alcoholic extract of Tinospora cordifolia in an in vivo rat model. The model adopted was that of surgically-induced myocardial ischemia, performed by means of left anterior descending coronary artery occlusion (LAD) for 30 min followed by reperfusion for another 4 h. Infarct size was measured by using the staining agent TTC (2,3,5-triphenyl tetrazolium chloride). Lipid peroxide levels in serum and in heart tissue were estimated spectrophotometrically by the methods developed by Yagi and Ohkawa et al respectively. A lead II electrocardiogram was monitored at various intervals throughout the experiment. A dose dependent reduction in infarct size and in lipid peroxide levels of serum and heart tissue were observed with the prior treatment of T. cordifolia with various doses for 7 d compared to control animals. Hence, the present study suggests the cardioprotective activity of T. cordifolia in limiting ischemia-reperfusion induced myocardial infarction.

R. D. Bapat et al27 Percutaneous Transhepatic Biliary Drainage (PTBD) is performed in surgical jaundice to decompress the biliary tree and improve hepatic functions. However, the risk of sepsis is high in these patients due to immunosuppression and surgical outcome remains poor. This raises a question—can we do away with PTBD? To answer this query a study was carried out in 4 groups of patients bearing in mind the high incidence of sepsis and our earlier studies, which have demonstrated immunotherapeutic potential of Tinospora cordifolia (TC): (A) those undergoing surgery without PTBD (n = 14), (B) those undergoing surgery after PTBD (n = 13). The mortality was 57.14% in Group A as compared to 61.54% in Group B. Serial estimations of bilirubin levels carried out during the course of drainage (3 Wks) revealed a gradual and significant decrease from 12.52 ± 8.3 mg% to 5.85 ± 3.0 mg%. Antipyrine half-life did not change significantly (18.35 ± 4.2 hrs compared to basal values 21.96 ± 3.78 hrs). The phagocytic and intracellular killing (ICK) capacities of PMN remained suppressed (Basal: 22.13 ± 3.68% phago, and 19.1 ± 4.49% ICK; Post drainage: 20 ± 8.48% Phago and 11.15 ± 3.05% ICK). Thus PTBD did not improve the metabolic capacity ofthe liver and mortality was higher due to sepsis. Group (C) patientg received TC during PTBD (n = 16) and Group (D) patients received TC without PTBD (n = 14). A significant improvement in PMN functions occurred by 3 weeks in both groups (30.29 ± 4.68% phago, 30 ± 4.84% ICK in Group C and 30.4 ± 2.99% phago, 27.15 ± 6.19% ICK in Group D). The mortality in Groups C and D was 25% and 14.2% respectively during the preoperative period. There was no mortality after surgery. It appears from this study that host defenses as reflected by PMN functions play an important role in influencing prognosis. Further decompression of the biliary tree by PTBD seems unwarranted.

Bafna PA et al 28 Pepticare, a herbomineral formulation of the Ayurveda medicine consisting of the herbal drugs: Glycyrrhiza glabra, Emblica officinalis and Tinospora cordifolia, was tested for its anti-ulcer and anti-oxidant activity in rats. Effects of various doses (125, 250, 500 and 1000mg/kg, p.o.) of Pepticare were studied on gastric secretion and gastric ulcers in pylorus-ligation and on ethanol-induced gastric mucosal injury in rats. The reduction in ulcer index in both the models along with the reduction in volume and total acidity, and an increase in the pH of gastric fluid in pylorus-ligated rats proved the anti-ulcer activity of Pepticare. It was also found that Pepticare was more potent than G. glabra alone in protecting against pylorus-ligation and ethanol-induced ulcers. The increase in the levels of superoxide dismutase, catalase, reduced glutathione and membrane bound enzymes like Ca2+ ATPase, Mg2+ ATPase and Na+ K+ ATPase and decrease in lipid peroxidation in both the models proved the anti-oxidant activity of the formulation. Thus it can be concluded that Pepticare possesses anti-ulcer activity, which can be attributed to its anti-oxidant mechanism of action.

Prince PS et al29 We made an attempt to study the antioxidant properties of Tinospora cordifolia roots, an indigenous plant used in Ayurvedic medicine in India in alloxan diabetic rats. Oral administration of an aqueous T. cordifolia root extract (TCREt) (2.5 and 5.0 g/kg) for 6 weeks resulted in a decrease in the levels of plasma thiobarbituric acid reactive substances, ceruloplasmin and alpha-tocopherol in alloxan diabetic rats. The root extract also causes an increase in the levels of glutathione and vitamin C in alloxan diabetes. The root extract at a dose of 5.0 g/kg showed the highest effect. The effect of TCREt was more effective than glibenclamide. Insulin restored all the parameters to near normal levels.
 
Dhuley JN et al30 The effect of Indian herbs namely, Asparagus racemosus, Tinospora cordifolia, Withania somnifera and Picrorhiza kurrooa on the functions of macrophages obtained from mice treated with the carcinogen ochratoxin A (OTA) was investigated. The chemotactic activity of murine macrophages was significantly decreased by 17 weeks of treatment with OTA compared with controls. Production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) was also markedly reduced. Treatment with Asparagus racemosus, Tinospora cordifolia, Withania somnifera and Picrorhiza kurrooa significantly inhibited OTA-induced suppression of chemotactic activity and production of IL-1 and TNF-alpha by macropahges. Moreover, we found that Withania somnifera treated macrophage chemotaxis and that Asparagus racemosus induced excess production of TNF-alpha when compared with controls.

Wadood N et al31 The aqueous, alcoholic, and chloroform extracts of the leaves of Tinospora cordifolia were administered in doses of 50, 100, 150 and 200 mg/kg body weight to normal and alloxan-diabetic rabbits. The blood glucose and total lipid levels were estimated before and 2, 4, 6, and 8 hours after administration of the extract. The extract exerted a significant (P less than 0.5) hypoglycaemic effect in normal as well as in alloxan-treated rabbits. The extracts, however, had no significant (P greater than 0.05) effect on total lipid levels in normal as well as in alloxan-treated diabetic rabbits. The doses used did not show acute toxicity or result in behavioural changes. From this study, it may be concluded that extracts of the leaves of Tinospora cordifolia have an insulin-like action and can significantly reduce the blood glucose but not the total lipid levels in normal rabbits and in alloxan-induced diabetic rabbits..

Singh L et al32 Tinospora cordifolia (RTc) has already been reported to protect whole-body lethally irradiated mice. This study has focused on certain aspects of immuno-competence, which are adversely affected by irradiation. This study included estimation of spleen size, cell count, DNA fragmentation and apoptosis in splenocytes. The adherence, spreading and phagocytic activities of macrophages were also assessed. Cytokines in serum and anti-oxidants in plasma were also estimated. Administration of RTc (200 mg/kg.b.wt.) one hour before irradiation showed recovery of spleen weight from 49% of control in irradiated group to 93%; apoptosis from 19% to 2.8%; DNA fragmentation from 43% to 20.4%; macrophage adherence form 75% of control to 120% and macrophage spread size from 8 microm to 15 microm. RTc also stimulated proliferation in splenocytes in a dose-dependent manner. RTc administration before irradiation also increased levels of IL-1beta and GM-CSF levels, from 56 pg/ml and 53 pg/ml respectively in irradiated group to 59 pg/ml and 63 pg/ml. Similarly, radiation-induced decrease of anti-oxidant potential of plasma (32 Fe(2+) equiv.) as compared to control (132 Fe(2+) equiv.) was countered by administration of RTc before irradiation (74.2 Fe(2+) equiv.) RTc treatment thus reveals several radio-protective mechanisms.

Singh N et al33 This article presents evidence to show that an alcoholic extract of Tinospora cordifolia (ALTC) enhances the differentiation of TAM to dendritic cells (DC) in response to granulocyte/macrophage-colony-stimulating factor, interleukin-4, and tumor necrosis factor. DC differentiated in vitro from TAM that were harvested from tumor-bearing mice after i.p. administration of ALTC (200 mg/kg body weight) 2 days post tumor transplantation shows an enhanced tumor cytotoxicity and production of tumoricidal soluble molecules like TNF, IL-1, and NO. Adoptive transfer of these TAM-derived DC to Dalton's lymphoma-bearing mice resulted in prolongation of survival of tumor-bearing mice. This is the first report regarding the differentiation and antitumor functions of TAM-derived DC obtained from tumor-bearing host administered with ALTC. The possible mechanisms involved also are discussed.
 
Leyon PV et al34 The antiangiogenic activity of Tinospora cordifolia was studied using in vivo as well as in vitro models. In vivo antiangiogenic activity was studied using B16F10 melanoma cell-induced capillary formation in animals. Intraperitoneal administration of the extract at a concentration of 20 mg/kg significantly inhibited the tumour directed capillary formation induced by melanoma cells. Analysis of the serum cytokine profile showed a drastic increase of proinflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, granulocyte monocyte-colony stimulating factor (GM-CSF) and the direct endothelial cell proliferating agent vascular endothelial cell growth factor (VEGF) in the angiogenesis-induced control animals. Administration of Tinospora extract could differentially regulate these cytokine's elevation. The differential regulation is further evidenced by the increased production of antiangiogenic agents IL-2 and tissue inhibitor of metalloprotease-1 (TIMP-1) in the B16F10-injected, extract-treated animals. Moreover, using an in vitro rat aortic ring assay, it was observed that the extract at nontoxic concentrations inhibited the production of proangiogenic factors from B16F10 melanoma cells. Direct treatment of the extract also inhibits the microvessel outgrowth from the aortic ring. Hence, the observed antiangiogenic activity of the plant T. cordifolia is related, at least in part, to the regulation of the levels of these cytokines and growth factors in the blood of the angiogenesis-induced animal. 

Bhattacharya SK et al35 Diabetes mellitus was induced in male CF strain rats by streptozotocin (STZ) and hyperglycaemia and superoxide dismutase (SOD) activity of pancreatic islet cells was assessed on days 7, 14, 21 and 28. STZ induced significant hyperglycaemia and a concomitant decrease in islet cell SOD activity. Transina (TR), an Ayurvedic herbal formulation comprising of Withania somnifera, Tinospora cordifolia, Eclipta alba, Ocimum sanctum, Picrorrhiza kurroa and shilajit, had little per se effect on blood sugar concentrations and islet SOD activity in euglycaemic rats, in the doses of 100 and 200 mg/kg, p.o. administered once daily for 28 days. However, these doses of TR induced a dose- related decrease in STZ hyperglycaemia and attenuation of STZ induced decrease in islet SOD activity. The results indicate that the earlier reported anti-hyperglycaemic effect of TR may be due to pancreatic islet free radical scavenging activity, the hyperglycaemic activity of STZ being the consequence of decrease in islet SOD activity leading to the accumulation of degenerative oxidative free radicals in islet beta-cells.

Badar VA et al36 The efficacy of Tinospora cordifolia (TC) extract in patients of allergic rhinitis was assessed in a randomized double blind placebo controlled trial Seventy-five patients were randomly given either TC or placebo for 8 weeks. They were clinically examined and Hb %, TLC, DLC and nasal smear was done. At the end of trial baseline investigations were repeated, drug decoded and results analyzed. With TC treatment 100% relief was reported from sneezing in 83% patients, in 69% from nasal discharge, in 61% from nasal obstruction and in 71% from nasal pruritus. In placebo group, there was no relief in 79% from sneezing, in 84.8% from nasal discharge, in 83% from nasal obstruction, and in 88% from nasal pruritus. The difference between TC and placebo groups was highly significant. TLC increased in 69% patients in drug treated group and in only 11% with placebo. After TC, eosinophil and neutrophil count decreased and goblet cells were absent in nasal smear. After placebo, decrease in eosinophil and neutrophil count was marginal and goblet cells were present. TC significantly decreased all symptoms of allergic rhinitis. Nasal smear cytology and leukocyte count correlated with clinical findings. TC was well tolerated.

Roja G et al37 Immobilized callus cultures of Tinospora cordifolia (Willd) Miers ex Hooks and Thoms were investigated to find out the combined effect of elicitation, cell permeabilization with chitosan and in situ product recovery by polymeric neutral resin-like Diaion HP 20. In this study, callus cultures of T. cordifolia were immobilized using sodium alginate and calcium chloride and the beads were cultured in Murashige and Skoog's basal medium along with benzyl adenine (BA), 2,4-dichlorophenoxy acetic acid (2,4-D) and 3% sucrose. The immobilized cultures, when subjected to elicitation and cell permeabilization with chitosan and in situ removal of the secondary metabolites by addition of resin, showed a 10-fold increase in production of arabinogalactan (0.490% dry weight) as compared to respective controls devoid of resin and chitosan. This indicates that in situ adsorption may have reduced the feedback inhibition caused by accumulation of secondary metabolites in the media, while the dual effect of elicitation and cell permeabilization by chitosan may have released the intracellular (secreted) berberine and the polysaccharide arabinogalactan, respectively.

Jagetia GC et al38 The anticancer activity of dichloromethane extract of guduchi in the mice transplanted with Ehrlich ascites carcinoma (EAC) was investigated. The EAC mice receiving 25, 30, 40, 50 and 100 mg/kg, TCE showed a dose dependent elevation in tumor-free survival and a highest number of survivors were observed at 50 mg/kg TCE, which was considered as an optimum dose for its neoplastic action. The average survival time (AST) and median survival time (MST) for this dose were approximately 56 and 55 d, respectively when compared with 19 d of non-drug treated controls. Administration of 50 mg/kg TCE resulted in 100% long-term survivors (up to 90 d). An attempt was also made to evaluate the effectiveness of TCE in the various stages of tumor development, where 50 mg/kg TCE was administered intraperitoneally after 1, 3, 6, 9, 12 or 15 d of tumor inoculation and these days have been arbitrarily designated as stage I, II, III, IV or V, respectively for reasons of clarity. The greatest anticancer activity was recorded for stage I, II and III where number of long term survivors (LTS) was approximately 33, 25 and 17%, respectively. However, treatment of mice at stage IV and V did not increase LTS, despite an increase in AST and MST. The EAC mice receiving 50 mg/kg TCE showed a time dependent depletion in the glutathione (GSH) activity up to 12 h post-treatment and marginal elevation thereafter. This depletion in GSH was accompanied by a drastic elevation in lipid peroxidation (LPx) and a maximum elevation in LPx was observed at 6 h that declined gradually thereafter. TCE exerted cytotoxic effect on tumor cells by reducing the GSH concentration and increase in LPx simultaneously.
 
Jagetia GC et al39 Exposure of HeLa cells to 0, 5, 10, 25, 50 and 100 microg/ml of guduchi extracts (methanol, aqueous and methylene chloride) resulted in a dose-dependent but significant increase in cell killing, when compared to non-drug-treated controls. The effects of methanol and aqueous extracts were almost identical However, methylene chloride extract enhanced the cell killing effect by 2.8- and 6.8-fold when compared either to methanol or aqueous extract at 50 and 100 microg/ml, respectively. Conversely, the frequency of micronuclei increased in a concentration-dependent manner in guduchi-treated groups and this increase in the frequency of micronuclei was significantly higher than the non-drug-treated control cultures and also with respect to 5 microg/ml guduchi extract-treated cultures, at the rest of the concentrations evaluated. Furthermore, the micronuclei formation was higher in the methylene chloride extract-treated group than in the other two groups. The dose response relationship for all three extracts evaluated was linear quadratic. The effect of guduchi extracts was comparable or better than doxorubicin treatment. The micronuclei induction was correlated with the surviving fraction of cells and the correlation between cell survival and micronuclei induction was found to be linear quadratic. Our results demonstrate that guduchi killed the cells very effectively in vitro and deserves attention as an antineoplastic agent.

Kapur P et al 40 Present animal studies were conducted to investigate the potential of Tinospora cordifolia (TC) ethanolic stem extract as an antiosteoporotic agent. METHODS: Three-month-old female Sprague-Dawley rats were either ovariectomized (ovx) or sham operated and treated with vehicle (benzyl benzoate:castor oil; 1:4), E(2) (1 microg/day) or TC (10, 50, 100 mg/kg b.wt) subcutaneously for 4 weeks. At the end of experiment bone mineral density of tibiae was measured by quantitative computer tomography. Serum was analyzed for the activity of alkaline phosphatase and levels of osteocalcin, cross-laps and lipids. Uterus and mammary gland were processed for histological studies. RESULTS: Ovx rats treated with TC (10 mg/kg b.wt) showed an osteoprotective effect as the bone loss in tibiae was slower than ovx controls. Serum osteocalcin and cross-laps levels were significantly reduced. All the above effects of TC were much milder than those produced by E(2). Alkaline phosphatase activity was higher in TC treatment groups. Total cholesterol and LDL levels remained unaltered but HDL levels were significantly lowered with TC (50 mg/kg b.wt) treatment. Uterus and mammary gland showed no signs of proliferation after treatment with TC extract. CONCLUSION: TC extract showed estrogen like effects in bone but not in reproductive organs like uterus and mammary gland. Thus, this study demonstrates that extract of T. cordifolia has the potential for being used as antiosteoporotic agent.

Singh N et al41 The present investigations were under taken to study whether the tumor-associated macrophages (TAM) of Dalton's lymphoma (DL), a spontaneous transplantable T cell lymphoma, can be activated by the alcoholic extract of medicinal plant Tinospora cordifolia (ALTC). Intraperitoneal administration of ALTC in DL-bearing mice not only augments the basic function of macrophages such as Phagocytosis as well as their antigen presenting ability and secretion of IL-1, TNF and RNI. The results of the present investigation also indicate that the intraperitoneal administration of ALTC slow down the tumor growth and increases the life span of tumor bearing host, thus showing its anti tumor effect through destabilizing the membrane integrity of DL cells directly or indirectly. This is the first study of it's kind regarding the effect of alcoholic extract of Tinospora cordifolia on the activation of tumor associated macrophages and showing the antitumor effect on the spontaneous T-cell lymphoma (DL), thus may have clinical implications.

Atal CK et al42 The immunobiological activity was investigated of certain medicinal plants widely used in the Ayurvedic and Unani systems of medicine for treatment of chronic infections and immunological disorders. The effect of an ethanolic extract of each drug was studied on delayed type hypersensitivity, humoral responses to sheep red blood cells, skin allograft rejection, and phagocytic activity of the reticuloendothelial system in mice. Picrorhiza kurroa was found to be a potent immunostimulant, stimulating both cell-mediated and humoral immunity. Tylophora indica, Aconitum heterophyllum and Holarrhena antidysenterica appeared to stimulate phagocytic function while inhibiting the humoral component of the immune system. Tinospora cordifolia and Ocimum gratissimum appeared to improve the phagocytic function without affecting the humoral or cell-mediated immune system. Hemidesmus indicus suppressed both the cell-mediated and humoral components of the immune system.

Nair PK et al43 An alpha-D-glucan (RR1) composed of (1-->4) linked back bone and (1-->6) linked branches with a molecular mass of >550 kDa and exhibiting unique immune stimulating properties is isolated and characterized from the medicinal plant Tinospora cordifolia. This novel polysaccharide is noncytotoxic and nonproliferating to normal lymphocytes as well as tumor cell lines at 0-1000 microg/ml. It activated different subsets of the lymphocytes such as natural killer (NK) cells (331%), T cells (102%), and B cells (39%) at 100 microg/ml concentration. The significant activation of NK cells is associated with the dose-dependent killing of tumor cells by activated normal lymphocytes in a functional assay. Immune activation by RR1 in normal lymphocytes elicited the synthesis of interleukin (IL)-1beta (1080 pg/ml), IL-6 (21,833 pg/ml), IL-12 p70 (50.19 pg/ml), IL-12 p40 (918.23 pg/ml), IL-18 (27.47 pg/ml), IFN- gamma (90.16 pg/ml), tumor necrosis factor (TNF)-alpha (2225 pg/ml) and monocyte chemoattractant protein (MCP)-1 (2307 pg/ml) at 100 microg/ml concentration, while it did not induce the production of IL-2, IL-4, IL-10, interferon (IFN)-alpha and TNF-beta. The cytokine profile clearly demonstrates the Th1 pathway of T helper cell differentiation essential for cell mediated immunity, with a self-regulatory mechanism for the control of its overproduction. RR1 also activated the complements in the alternate pathway, demonstrated by a stepwise increase in C3a des Arg components. Incidentally, RR1 stimulation did not produce any oxidative stress or inducible nitric oxide synthase (iNOS) in the lymphocytes or any significant increase in nitric oxide production. The water solubility, high molecular mass, activation of lymphocytes especially NK cells, complement activation, Th1 pathway-associated cytokine profile, together with a low level of nitric oxide synthesis and absence of oxidative stress confer important immunoprotective potential to this novel alpha-D-glucan.

Stanely Mainzen Prince P etal45 We undertook the present study to evaluate the hypolipidaemic effect of an aqueous extract of Tinospora cordifolia roots, an indigenous plant used in Ayurvedic medicine in India. Administration of the extract of T. cordifolia roots (2.5 and 5.0 g/kg body weight) for 6 weeks resulted in a significant reduction in serum and tissue cholesterol, phospholipids and free fatty acids in alloxan diabetic rats. The root extract at a dose of 5.0 g/kg body weight showed highest hypolipidaemic effect. The effect of T. cordifolia roots at 2.5 and 5.0 g/kg body weight was better than glibenclamide. Insulin restored all the parameters to near normal values.
 
Stanely P et al46 has evaluate hypoglycaemic and other related actions of aqueous Tinospora cordifolia  roots in alloxan-induced diabetic rats. It has found that extract of Tinospora cordifolia has been shown that a significant reduction in blood glucose and brain lipids in alloxan diabetic rats.

Stanely Mainzen Prince P et al47 Tinospora cordifolia is widely used in Indian Ayurvedic medicine for treating diabetes mellitus. Oral administration of an aqueous T. cordifolia root extract (TCREt) to alloxan diabetic rats caused a significant reduction in blood glucose and brain lipids. The extract caused an increase in body weight, total haemoglobin and hepatic hexokinase. The root extract also lowers hepatic glucose-6-phosphatase and serum acid phosphatase, alkaline phosphatase, and lactate dehydrogenase in diabetic rats. Thus TCREt has hypoglycaemic and hypolipidaemic effect.
Bishayi B et al49 Effect of Tinospora cordifolia extract on modulation of hepatoprotective and immunostimulatory functions in carbon tetrachloride (CCl4) intoxicated mature rats is reported here. Administration of CCl4 (0.7 ml/kg body weight for 7 days) produces damage in the liver as evident by estimation of enzymes such as serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transminase (SGPT) and alkaline phosphatase (ALP) as well as serum bilirubin level. CCl4 administration also causes immunosuppressive effects as indicated by phagocytic capacity, chemotactic migration and cell adhesiveness of rat peritoneal macrophages. However, treatment with T. cordifolia extract (100 mg/kg body weight for 15 days) in CCl4 intoxicated rats was found to protect the liver, as indicated by enzyme level in serum. A significant reduction in serum levels of SGOT, SGPT, ALP, bilirubin were observed following T. cordifolia treatment during CCl4 intoxication. Treatment with T. cordifolia extract also deleted the immunosuppressive effect of CCl4, since a significant increment in the functional capacities of rat peritoneal macrophages (PM phi) was observed following T. cordifolia treatment. The results of our experiment suggest that treatment by T. cordifolia extract may be the critical remedy for the adverse effect of CCl4 in liver function as well as immune functions.

Desai VR et al50 Pro-inflammatory cytokines are known to be the mediators of endotoxic shock and several immunomodulatory herbs can modulate the expression of these cytokines. Therefore we have investigated the possibility of using an arabinogalactan polysaccharide, G1-4A, from the stem of Tinospora cordifolia, for protection against endotoxin induced sepsis. There was 100% protection against lipopolysaccharide (LPS) induced mortality in mice pretreated with G1-4A. To elucidate the mechanism of action, its effect on macrophages, the primary source of these pro-inflammatory molecules was evaluated. G1-4A was shown to bind to the murine macrophages leading to their activation and reciprocally inhibited binding of LPS to macrophages. Following treatment with G1-4A, there was a small increase in serum TNF-alpha and IL-1beta levels. However, challenge with LPS elicited significantly reduced levels of TNF-alpha in G1-4A pretreated mice as compared to the controls while the level of soluble TNFR was enhanced. An increase in serum IL-1beta, IL-6, IFN-gamma levels and decrease in that of IL-10 was observed following challenge with LPS in mice pretreated with G1-4A as compared to the controls. In addition, G1-4A also modulated the release of nitric oxide by murine macrophages. Similar phenomenon was observed in a human monocytic cell line, U937. Thus G1-4A appeared to induce tolerance against endotoxic shock by modulation of cytokines and nitric oxide.

Diwanay S et al51 Most of the synthetic chemotherapeutic agents available today are immunosuppressants, cytotoxic, and exert variety of side effects that are particularly evident in cancer chemotherapy. Botanical based immunomodulators are often employed as supportive or adjuvant therapy to overcome the undesired effects of cytotoxic chemotherapeutic agents and to restore normal health. Total extract, polar and non-polar extracts, and their formulations, prepared from medicinal plants mentioned in Ayurveda, namely, Withania somnifera (Linn Dunal) (Solanaceae), Tinospora cordifolia (Miers) (Menispermaceae), and Asparagus racemosus (Willd.) (Liliaceae), exhibited various immunopharmacological activities in cyclophosphamide (CP)-treated mouse ascitic sarcoma. Treatment of ascitic sarcoma-bearing mice with a formulation of total extracts of Withania somnifera and Tinospora cordifolia (80:20) and alkaloid-free polar fraction of Withania somnifera resulted in protection towards CP-induced myelo- and immunoprotection as evident by significant increase in white cell counts and hemagglutinating and hemolytic antibody titers. Treatment with these candidate drugs will be important in development of supportive treatment with cancer chemotherapy.

Sudhakaran DS et al52 Immunostimulatory effect of leaf extract of T. cordifolia on (i) specific immunity (antibody response), (ii) non-specific immunity (neutrophil activity) and (iii) disease resistance against Aeromonas hydrophila was investigated in O. mossambicus. Ethanol and petroleum ether extracts of the leaves were used. Both ethanol and petroleum ether extracts administered at doses of 0.8, 8 or 80 mg/kg body weight, prolonged the peak primary antibody titres upto one to three weeks. Ethanol extract at the dose of 8 mg/kg and petroleum ether extract at the doses of 0.8 or 8 mg/kg enhanced the secondary antibody response. All the doses of ethanol extract significantly enhanced neutrophil activity. Fish injected with petroleum ether or ethanol extract at a dose of 8 mg/kg were protected against experimental infection with virulent A. hydrophila. The results indicates the potential of T. cordifolia leaf extracts for use as an immunoprophylactic to prevent diseases in finfish aquaculture.

Rege N et al53 Objective of the study was immunosuppression associated with deranged hepatic function and sepsis results in poor surgical outcome in extrahepatic obstructive jaundice. The effect of an ayurvedic agent, Tinospora cordifolia (TC), which has been shown to have hepatoprotective and immunomodulatory properties in experimental studies, on surgical outcome in patients with malignant obstructive jaundice was evaluated. METHODS: Thirty patients were randomly divided into two groups, matched with respect to clinical features, impairment of hepatic function (as judged by liver function tests including antipyrine elimination) and immunosuppression (phagocytic and killing capacities of neutrophils). Group I received conventional management, ie vitamin K, antibiotics and biliary drainage; Group II received Tinospora cordifolia (16 mg/kg/day orally) in addition, during the period of biliary drainage. RESULTS: Hepatic function remained comparable in the two groups after drainage. However, the phagocytic and killing capacities of neutrophils normalized only in patients receiving Tinospora cordifolia (28.2 +/- 5.5% and 29.47 +/- 6.5% respectively). Post-drainage bactobilia was observed in 8 patients in Group I and 7 in Group II, but clinical evidence of septicemia was observed in 50% of patients in Group I as against none in Group II (p < 0.05). Post-operative survival in Groups I and II was 40% and 92.4% respectively (p < 0.01). CONCLUSION: Tinospora cordifolia appears to improve surgical outcome by strengthening host defenses.

Modak M et al54 Traditional Medicines derived from medicinal plants are used by about 60% of the world's population. This review focuses on Indian Herbal drugs and plants used in the treatment of diabetes, especially in India. Diabetes is an important human ailment afflicting many from various walks of life in different countries. In India it is proving to be a major health problem, especially in the urban areas. Though there are various approaches to reduce the ill effects of diabetes and its secondary complications, herbal formulations are preferred due to lesser side effects and low cost. A list of medicinal plants with proven antidiabetic and related beneficial effects and of herbal drugs used in treatment of diabetes is compiled. These include, Allium sativum, Eugenia jambolana, Momordica charantia Ocimum sanctum, Phyllanthus amarus, Pterocarpus marsupium, Tinospora cordifolia, Trigonella foenum graecum and Withania somnifera. One of the etiologic factors implicated in the development of diabetes and its complications is the damage induced by free radicals and hence an antidiabetic compound with antioxidant properties would be more beneficial Therefore information on antioxidant effects of these medicinal plants is also included.

Manisha Modak et al55Traditional Medicines derived from medicinal plants are used by about 60% of the world’s population. This review focuses on Indian Herbal drugs and plants used in the treatment of diabetes, especially in India. Diabetes is an important human ailment afflicting many from various walks of life in different countries. In India it is proving to be a major health problem, especially in the urban areas. Though there are various approaches to reduce the ill effects of diabetes and its secondary complications, herbal formulations are preferred due to lesser side effects and low cost. A list of medicinal plants with proven antidiabetic and related beneficial effects and of herbal drugs used in treatment of diabetes is compiled. These include, Allium sativum, Eugenia jambolana, Momordica charantia Ocimum sanctum, Phyllanthus amarus, Pterocarpus marsupium, Tinospora cordifolia, Trigonella foenum graecum and Withania somnifera. One of the etiologic factors implicated in the development of diabetes and its complications is the damage induced by free radicals and hence an antidiabetic compound with antioxidant properties would be more beneficial Therefore information on antioxidant effects of these medicinal plants is also included.

Citarasu T et al56 Immunostimulants are the substances, which enhance the non-specific defence mechanism and provide resistance against the invading pathogenic micro-organism. In order to increase the immunity of shrimps against the WSSV, the methanolic extracts of five different herbal medicinal plants like Cyanodon dactylon, Aegle marmelos, Tinospora cordifolia, Picrorhiza kurooa and Eclipta alba were selected and mixed thoroughly in equal proportion. The mixed extract was supplemented with various concentrations viz. 100 (A), 200 (B), 400 (C), and 800 (D) mgkg(-1) through artificial diets individually. The prepared diets (A-D) were fed individually to WSSV free healthy shrimp Penaeus monodon with an average weight of 8.0+/-0.5g for 25 days. Control diet (E), devoid of herbal extract was also fed to shrimps simultaneously. After 25 days of feeding experiment, the shrimps were challenged with WSSV, which were isolated and propagated from the infected crustaceans. The shrimps succumbed to death within 7 days when fed on no herbal immunostimulant diet (E). Among the different concentrations of herbal immunostimulant supplemented diets, the shrimps fed on diet D (800mgkg(-1)) significantly (P<0.0001) had more survival (74%) and reduction in the viral load. Also the better performance of haematological, biochemical and immunological parameters was found in the immunostimulant incorporated diets fed shrimps. The present work revealed that the application of herbal immunostimulants will be effective against shrimp viral pathogenesis and they can be recommended for shrimp culture.

Leyon PV et al57 Administration of the polysaccharide fraction from Tinospora cordifolia was found to be very effective in reducing the metastatic potential of B16F-10 melanoma cells. There was a 72% inhibition in the metastases formation in the lungs of syngeneic C57BL/6 mice, when the drug was administered simultaneously with tumour challenge. Biochemical parameters such as lung collagen hydroxyproline, hexosamines and uronic acids that are markers of neoplastic development were reduced significantly (P<0.001) in the treated animals compared with the untreated control animals. The treatment could also reduce serum gamma-glutamyltranspeptidase (gamma-GT) and sialic acid levels as compared to the control animals.

Prince PS et al59 The present study investigates the effect of oral administration of an alcoholic extract of Tinospora cordifolia roots on antioxidant defence in alloxan-induced diabetes in rats. A significant increase in the concentration of thiobarbituric acid reactive substances (TBARS) in brain along with a decrease in heart was observed in diabetic rats. Decreased concentration of glutathione (GSH) and decreased activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) in heart and brain of diabetic rats were also noted. Alcoholic Tinospora cordifolia root extract (TCREt) administered at a dose of 100 mg/kg to diabetic rats orally for six weeks normalized the antioxidant status of heart and brain. The effect of T. cordifolia root extract was more prominent than glibenclamide (600 microg/kg). Insulin (6 units/kg) restored all the parameters to normal status.

Goel HC et al60 has evaluate the radioprotective potential of an herbal extract of Tinospora cordifolia in the dose of 200 mg/kg. It has found that extract of Tinospora cordifolia has been shown  the radioprotective manifestation of RTc observed in several systems in experimental animals can be exploited for human applications.

Rege NN et al61 A preparation of Tinospora cordifolia (RTc) administered i.p. (200 mg/kg b.w.) to strain "A" male mice 1 h before whole body gamma-irradiation was evaluated for its radioprotective efficacy in terms of whole body survival, spleen colony forming units (CFU), hematological parameters, cell cycle progression, and micronuclei induction. Preirradiation treatment with RTc rendered 76.3% survival (30 days), compared to 100% mortality in irradiated control and prevented radiation induced weight loss. On 10th postirradiation day, the endogenous CFU counts in spleen were decreased with increasing radiation doses 12.0 (5 Gy), 2.16 (7.5 Gy) and 0.33 (10 Gy) but pre-irradiation administration of 200 mg/kg b.w. of RTc increased CFU counts to 31.16, 21.83 and 3.00 respectively. Pre-irradiation RTc treatment could restore total lymphocyte counts (TLC) by the 15th day to normal It also increased the S-phase cell population that was reduced following 2 Gy irradiation in a time dependent manner. 2 Gy irradiation-induced micronuclei were also decreased by a pre-irradiation administration of RTc from 2.9 to 0.52%. Because the radioprotective manifestation of RTc observed in several systems in experimental animals can be exploited for human applications.

Panchabhai TS et al62 This study investigated the hepatoprotective effect of two Indian medicinal plants Tinospora cordifolia (Tc), Phyllanthus emblica (Pe), and their combination, in a rat model of isoniazid, rifampicin and pyrazinamide induced hepatic damage. Hepatic damage was assessed using a composite score assigned to histopathological findings of degeneration, necrosis and fibrosis. The antituberculosis treatment (ATT), when given for 90 days, induced significant degeneration and necrosis (score: 7.5; p < 0.01 vs vehicle) associated with morphological changes. However, no change was found in the serum bilirubin and liver enzymes. Co-administration of silymarin (positive control, 50 mg/kg) with ATT protected against necrosis (score: 1.5; p < 0.001 vs ATT). Tc (100 mg/kg) showed a reduction in liver damage (score: 6.5), which was not statistically significant. On the other hand, Pe (300 mg/kg) prevented the necrotic changes to a significant extent (grade: 100; p < 0.05 vs ATT; score: 5.5). Combination of Tc and Pe in their therapeutic doses (1:3) significantly prevented the necrosis (score: 3.5; p < 0.001 vs ATT). Similar effects were seen even when the doses were halved and were comparable to the silymarin group. Thus, this study proves the synergistic protective effects exerted by the combination of Tc and Pe when co-administered with ATT.

Jena GB et al63 has evaluate Protective effect of a polyherbal formulation (Immu-21) against cyclophosphamide-induced mutagenicity in mice. It has found that extract of Tinospora cordifolia has been shown that chronic treatment with Immu-21 prevented CP-induced genotoxicity in mice. The object was to evaluate the effects of a polyherbal formulation, Immu-21, against cyclophosphamide (CP)-induced chromosomal aberrations (CA) and micronuclei (MN) in mice. CP alone (40 mg/kg, i.p.) produced classical as well as non-classical chromosomal aberrations in mice, and the incidence of CA was significantly more in the CP treated group when compared with that of the control group. Immu-21, which contains extracts of Ocimum sanctum, Withania somnifera, Emblica officinalis and Tinospora cordifolia, was given at 100 mg/kg, daily, over 7 days, and 30 mg/kg daily over 14 days and inhibited both CP-induced classical and non-classical chromosomal aberrations ( approximately 40%-60% of control). A significant increase in MN was also observed in bone marrow erythrocytes of mice treated with CP, and pretreatment with Immu-21 also significantly reduced these. Cytotoxicity was evaluated by estimating the ratio of polychromatic erythrocytes (PCEs) to normochromatic erythrocytes (NCEs). The present results indicate that chronic treatment with Immu-21 prevented CP-induced genotoxicity in mice. 

Adhvaryu MR et al64 AIM: To evaluate the ability of Curcuma longa (CL) and Tinospora cordifolia (TC) formulation to prevent anti-tuberculosis (TB) treatment (ATT) induced hepatotoxicity. METHODS: Patients with active TB diagnosis were randomized to a drug control group and a trial group on drugs plus an herbal formulation. Isoniazid, rifampicin, pyrazinamide and ethambutol for first 2 mo followed by continuation phase therapy excluding Pyrazinamide for 4 mo comprised the anti-tuberculous treatment. Curcumin enriched (25%) CL and a hydro-ethanolic extract enriched (50%) TC 1 g each divided in two doses comprised the herbal adjuvant. Hemogram, bilirubin and liver enzymes were tested initially and monthly till the end of study to evaluate the result. RESULTS: Incidence and severity of hepatotoxicity was significantly lower in trial group (incidence: 27/192 vs 2/316, P < 0.0001). Mean aspartate transaminase (AST) (195.93 +/- 108.74 vs 85 +/- 4.24, P < 0.0001), alanine transaminase (ALT) (75.74 +/- 26.54 vs 41 +/- 1.41, P < 0.0001) and serum bilirubin (5.4 +/- 3.38 vs 1.5 +/- 0.42, P < 0.0001). A lesser sputum positivity ratio at the end of 4 wk (10/67 vs 4/137, P = 0.0068) and decreased incidence of poorly resolved parenchymal lesion at the end of the treatment (9/152 vs 2/278, P = 0.0037) was observed. Improved patient compliance was indicated by nil drop-out in trial vs 10/192 in control group (P < 0.0001). CONCLUSION: The herbal formulation prevented hepatotoxicity significantly and improved the disease outcome as well as patient compliance without any toxicity or side effects.

Rathi SS et al65 The efficacy of Momordica charantia (MC), Eugenia jambolana (EJ), Tinospora cordifolia (TC) and Mucuna pruriens (MP) was assessed in the prevention of murine alloxan dibetic cataract. Alloxan (120 mg/kg) was used as the diabetogenic agent. While controls and diabetic controls did not receive any plant extract, treated rats received lyophilized aqueous extract of MC and EJ (200 mg/kg p.o.), alcohol extract of TC (400 mg/kg) and MP (200 mg/kg p.o.) every day until 4 months. Serum glucose concentration was assessed and cataracts examined with both the naked eye and through a slit lamp. Of the eight animals in the diabetic control group, four developed cortical cataract (stage IV) by day 90 while the remaining four developed it by day 100. The incidence rate of cataract in MC, EJ, TC and MP treated groups at 120 days was only 0, 0, 1 and 2. Oral feeding of MC, EJ, TC and MP extracts for 1 month produced a fall of 64.33%, 55.62%, 38.01% and 40.17%, respectively, in the serum glucose levels in comparison with the 48 h level. After 2 months of treatment, the respective values were 66.96%, 59.85%, 40.41% and 45.63%. MC and EJ prevented the development of cataract while the protective effect was less with TC and MP along with a significant reduction of plasma glucose levels (p < 0.001).  

Thippeswamy G et al 66 The efficacy of Momordica charantia (MC), Eugenia jambolana (EJ), Tinospora cordifolia (TC) and Mucuna pruriens (MP) was assessed in the prevention of murine alloxan dibetic cataract. Alloxan (120 mg/kg) was used as the diabetogenic agent. While controls and diabetic controls did not receive any plant extract, treated rats received lyophilized aqueous extract of MC and EJ (200 mg/kg p.o.), alcohol extract of TC (400 mg/kg) and MP (200 mg/kg p.o.) every day until 4 months. Serum glucose concentration was assessed and cataracts examined with both the naked eye and through a slit lamp. Of the eight animals in the diabetic control group, four developed cortical cataract (stage IV) by day 90 while the remaining four developed it by day 100. The incidence rate of cataract in MC, EJ, TC and MP treated groups at 120 days was only 0, 0, 1 and 2. Oral feeding of MC, EJ, TC and MP extracts for 1 month produced a fall of 64.33%, 55.62%, 38.01% and 40.17%, respectively, in the serum glucose levels in comparison with the 48 h level. After 2 months of treatment, the respective values were 66.96%, 59.85%, 40.41% and 45.63%. MC and EJ prevented the development of cataract while the protective effect was less with TC and MP along with a significant reduction of plasma glucose levels (p < 0.001). 

Nagarkatti DS et al 67 Kupffer cells are major determinants of outcome of liver injury. Their activity was therefore studied in a model of chronic liver disease. The effect of Tinospora cordifolia, an indigenous agent with proven hepatoprotective activity, was evaluated on Kupffer cell function, using carbon clearance test as a parameter. Rats were divided into two major groups. In Gp I which served as normal control t1/2 of carbon was 9.48 +/- 4.14 min. GpII received horse-serum in a dose of 0.5 ml/100 gm b.w. i.p. for a period of 12 weeks and was divided into three sub-groups. In Gp IIA at the end of 12 weeks half-life of carbon was found to be significantly increased to 19.86 +/- 7.95 min (p < 0.01). Indicating suppressed Kupffer cell function in chronic liver damage. In Gp IIB treated with vehicle for 4 more weeks there was significant prolongation of half-life to 38.32 +/- 10.61 min (p < 0.01), indicating perpetuation of damage in absence of damaging agent. Whereas in Gp IIc, treated with Tinospora cordifolia t 1/2 was decreased to 14.24 7.74 min (p < .01), as compared to vehicle control indicating a significant improvement in Kupffer cell function and a trend towards normalization.

Rege NN et al68 Kupffer cells are major determinants of outcome of liver injury. Their activity was therefore studied in a model of chronic liver disease. The effect of Tinospora cordifolia, an indigenous agent with proven hepatoprotective activity, was evaluated on Kupffer cell function, using carbon clearance test as a parameter. Rats were divided into two major groups. In Gp I which served as normal control t1/2 of carbon was 9.48 +/- 4.14 min. GpII received horse-serum in a dose of 0.5 ml/100 gm b.w. i.p. for a period of 12 weeks and was divided into three sub-groups. In Gp IIA at the end of 12 weeks half-life of carbon was found to be significantly increased to 19.86 +/- 7.95 min (p < 0.01). Indicating suppressed Kupffer cell function in chronic liver damage. In Gp IIB treated with vehicle for 4 more weeks there was significant prolongation of half-life to 38.32 +/- 10.61 min (p < 0.01), indicating perpetuation of damage in absence of damaging agent. Whereas in Gp IIc, treated with Tinospora cordifolia t 1/2 was decreased to 14.24 7.74 min (p < .01), as compared to vehicle control indicating a significant improvement in Kupffer cell function and a trend towards normalization.

Spelman K et al69 Kupffer cells are major determinants of outcome of liver injury. Their activity was therefore studied in a model of chronic liver disease. The effect of Tinospora cordifolia, an indigenous agent with proven hepatoprotective activity, was evaluated on Kupffer cell function, using carbon clearance test as a parameter. Rats were divided into two major groups. In Gp I which served as normal control t1/2 of carbon was 9.48 +/- 4.14 min. GpII received horse-serum in a dose of 0.5 ml/100 gm b.w. i.p. for a period of 12 weeks and was divided into three sub-groups. In Gp IIA at the end of 12 weeks half-life of carbon was found to be significantly increased to 19.86 +/- 7.95 min (p < 0.01). Indicating suppressed Kupffer cell function in chronic liver damage. In Gp IIB treated with vehicle for 4 more weeks there was significant prolongation of half-life to 38.32 +/- 10.61 min (p < 0.01), indicating perpetuation of damage in absence of damaging agent. Whereas in Gp IIc, treated with Tinospora cordifolia t 1/2 was decreased to 14.24 7.74 min (p < .01), as compared to vehicle control indicating a significant improvement in Kupffer cell function and a trend towards normalization.

Singh N et al70 In vivo administration of alcoholic extract of medicinal plant Tinospora cordifolia (TC) to mice bearing a spontaneous T cell lymphoma designated as Dalton's lymphoma prevented tumor growth-dependent regression of thymus. TC was found to augment proliferation of thymocytes with a concomitant decrease in thymocyte apoptosis. It also resulted in a decrease in the number of Hassal's corpuscles. Restoration of thymus homeostasis was caused by TC-dependent augmentation in production of thymocyte growth promoting cytokines Interleukin-2 and Interferon-gamma from thymocytes. TC was found to downregulate thymocyte apoptosis by modulation of Caspase pathway. TC administration retarded tumor growth and prolonged survival of tumor-bearing mice. The possible mechanisms are discussed.

Avinash K Rawal et al71 The major damaging factor during and after the ischemic/hypoxic insult is the generation of free radicals, which leads to apoptosis, necrosis and ultimately cell death. Rubia cordifolia (RC), Fagonia cretica linn (FC) and Tinospora cordifolia (TC) have been reported to contain a wide variety of antioxidants and have been in use in the eastern system of medicine for various disorders. However, their mechanism of action was largely unknown. We therefore selected these herbs for the present study to test their neuroprotective ability and the associated mechanism in rat hippocampal slices subjected to oxygen-glucose deprivation (OGD). All the three herbs were effective in elevating the GSH levels, expression of the gamma-glutamylcysteine ligase and Cu-Zn SOD genes. The herbs also exhibited strong free radical scavenging properties against reactive oxygen and nitrogen species as studied by electron paramagnetic resonance spectroscopy. In addition all the three herbs significantly diminished the expression of iNOS gene after 48 hours which plays a major role in neuronal injury during hypoxia/ischemia.

Sohni YR et al72 The antiamoebic effect of a crude drug formulation against Entamoeba histolytica was studied. In the traditional system of medicine in India, the formulation has been prescribed for intestinal disorders. It comprises of five medicinal herbs, namely, Boerhavia diffusa, Berberis aristata, Tinospora cordifolia, Terminalia chebula and Zingiber officinale. The dried and pulverized plants were extracted in ethanol together and individually. In vitro amoebicidal activity was studied to determine the minimal inhibitory concentration (MIC) values of all the constituent extracts as well as the whole formulation. The formulation had a MIC of 1000 micrograms/ml as compared with 10 micrograms/ml for metronidazole. In experimental caecal amoebiasis in rats the formulation had a curative rate of 89% with the average degree of infection (ADI) reduced to 0.4 in a group dosed with 500 mg/kg per day as compared with ADI of 3.8 for the sham-treated control group of rats. Metronidazole had a cure rate of 89% (ADI = 0.4) at a dose of 100 mg/kg per day and cured the infection completely (ADI = 0) when the dosage was doubled to 200 mg/kg per day. There were varying degrees of inhibition of the following enzyme activities of crude extracts of axenically cultured amoebae: DNase, RNase, aldolase, alkaline phosphatase, acid phosphatase, alpha-amylase and protease.

Cingi C et al73 The prevalence of allergic rhinitis is increasing globally due to various causes. It affects the quality life of a large group of people in all around the world. Allergic rhinitis still remains inadequately controlled with present medical means. The need of continuous medical therapy makes individuals anxious about the side effects of the drugs. So there is a need for an alternative strategy. Effects of spirulina, Tinospora cordifolia and butterbur were investigated recently on allergic rhinitis in just very few investigations. Spirulina represents a blue-green alga that is produced and commercialized as a dietary supplement for modulating immune functions, as well as ameliorating a variety of diseases. This double blind, placebo controlled study, evaluated the effectiveness and tolerability of spirulina for treating patients with allergic rhinitis. Spirulina consumption significantly improved the symptoms and physical findings compared with placebo (P < 0.001***) including nasal discharge, sneezing, nasal congestion and itching. Spirulina is clinically effective on allergic rhinitis when compared with placebo. Further studies should be performed in order to clarify the mechanism of this effect.

Singh RK et al74 The effect of aqueous extract of Tinospora cordifolia, an immunomodulator with antimalarial activity along with chloroquine was studied in the treatment of three cases of hyper-reactive malarious splenomegaly in District Hospital, Daltonganj town, Jharkhand, India. These cases were partial/slow responders to the conventional antimalarial drug chloroquine. Aqueous extract of T. cordifolia (500 mg) was added to chloroquine (CQ) base (300 mg) weekly and CQ prophylaxis was observed up to six months. Improvement was gauzed by measuring spleen enlargement, Hb, serum IgM and well-being in three cases of hyper-reactive malarious splenomegaly.  Addition of extract of T. cordifolia for the first six weeks to chloroquine showed regression of spleen by 37-50% after six weeks and 45-69% after six months from the start of treatment. Likewise decrease in IgM and increase in Hb as well as wellbeing (Karnofsky performance scale) were observed.  The results of the present study paves a new sight in the treatment of hyper-reactive malarious splenomegaly, however, large-scale trial is required to confirm the beneficial effect of T. cordifolia extract in combination with chloroquine.

Thatte UM et al75 Tinospora cordifolia (Tc) is an Indian medicinal plant with proven immunomodulatory activity. This study was performed to elucidate its possible mechanism of action. We measured CFU-GM Cotony forming units of the granulocyte-macrophage series in serum of mice treated with Tc. We found that 10 days treatment with Tc (100 mg/ kg/d) induced a significant (p < 0.01) increase in the number of CFU-GM (255 +/- 49.32 vs 38.51 +/- 9.98) This suggests that activation of macrophages by Tc leads to increase in GM-CSF which leads to leucocytosis and improved neutrophil function.
 
Singh RP et al76 The present study is an effort to identify a potent chemopreventive agent against various diseases (including cancer) in which oxidative stress plays an important causative role. Here, we investigated the effect of a hydroalcoholic (80% ethanol: 20% distilled water) extract of aerial roots of Tinospora cordifolia (50 and 100mg/kg body wt./day for 2 weeks) on carcinogen/drug metabolizing phase-I and phase-II enzymes, antioxidant enzymes, glutathione (GSH) content, lactate dehydrogenase and lipid peroxidation in liver of 8-week-old Swiss albino mice. The modulatory effect of the extract was also examined on extrahepatic organs, i.e., lung, kidney and forestomach, for the activities of GSH S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD) and catalase. Significant increases in the levels of acid-soluble sulfhydryl (-SH) and cytochrome P(450) contents, and enzyme activities of cytochrome P(450) reductase, cytochrome b(5) reductase, GST, DTD, SOD, catalase, GSH peroxidase (GPX) and GSH reductase (GR) were observed in the liver. Both treated groups showed decreased malondialdehyde (MDA) formation. In lung SOD, catalase and GST; in kidney SOD and catalase; and in forestomach SOD, DTD and GST showed significant increase at both dose levels of treatment. BHA (0.75%, w/w in diet), a pure antioxidant compound, was used as a positive control. This group showed increase in hepatic levels of GSH content, cytochrome b(5), DTD, GST, GR and catalase, whereas MDA formation was inhibited significantly. In the BHA-treated group, the lung and kidney showed increased levels of catalase, DTD and GST, whereas SOD was significantly increased in the kidney and forestomach; the latter also showed an increase in the activities of DTD and GST. The enhanced GSH level and enzyme activities involved in xenobiotic metabolism and maintaining antioxidant status of cells are suggestive of a chemopreventive efficacy of T. cordifolia against chemotoxicity, including carcinogenicity, which warrants further investigation of active principle (s) present in the extract responsible for the observed effects employing various carcinogenesis models.

Grover JK et al77 The purpose of the study was to investigate the effects of daily oral feeding Momordica charantia (MC) (200 mg/kg), Eugenia jambolana (EJ) (200 mg/kg), Mucuna pruriens (MP) (200 mg/kg) and Tinospora cordifolia (TC) extracts for 40 days on blood glucose concentrations and kidney functions in streptozotocin (STZ)-diabetic rats. Plasma glucose levels, body weight, urine volume and urinary albumin levels were monitored on every 10th day over a 40-day period while plasma creatinine levels were assessed at the beginning and end of experiment. Renal hypertrophy was assessed as the ratio between the kidney weight and total body weight. Plasma glucose concentrations in STZ-diabetic mice were reduced by the administration of extracts of MC, EJ, TC and MP by 24.4, 20.84, 7.45 and 9.07%, respectively (P<0.005 for MC, EJ, MP and P<0.05 for TC). Urine volume was significantly higher (P<0.005) in diabetic controls and MC, EJ, MP and TC treatment prevented polyuria (P<0.001, 0.0001, 0.01 and 0.001, respectively). After 10 days of STZ administration urinary albumin levels (UAE) were over 6 fold higher in diabetic controls as compared to normal controls. Treatment with MC, EJ, MP and TC significantly prevented the rise in UAE levels from day 0 to 40 in comparison to diabetic controls (P<0.0001, 0.0001, 0.05, 0.05, respectively). Renal hypertrophy was significantly higher in diabetic controls as compared to non-diabetic controls. MC and EJ partially but significantly (P<0.05) prevented renal hypertrophy as compared to diabetic controls. TC and MP failed to modify renal hypertrophy. Results indicate that these plant drugs should be studied further.

Panchabhai TS et al78 This review article attempts to correlate Ayurvedic pharmacology and therapeutic claims for Tinospora cordifolia (Tc) with the evidence generated using scientific research methodology. In the present paper, a brief description of Ayurvedic pharmacology of the plant is presented. The work carried out by researchers using extracts of Tc in various areas such as diabetes, liver damage, free radical mediated injury, infections, stress and cancer have been reviewed. Also discussed are the immunomodulatory, diuretic, antiinflammatory, analgesic, anticholinesterase and gastrointestinal protective effects. An attempt has been made to provide the readers with the array of outcome variables, which can be further worked upon in clinical studies. Finally, this paper puts forth issues that need to be addressed by researchers in the future. 

Meghna R Adhvaryu et al79 AIM: To evaluate and compare the hepatoprotective and immunomodulatory effects of Curcuma longa (CL), Ocimum sanctum (OS), Tinospora cordifolia (TC) and Zizyphus mauritiana (ZM) on liver injury and immunosuppression induced by Isoniazid (INH), Rifampicin (RIF) and Pyrazinamide (PZA). Duncan Hartley guinea pigs, weighing 700-1050 g, were treated orally with 50 mg/kg of INH, 100 mg/kg of RIF and 300 mg/Kg of PZA for 21-d. 200 mg/kg (bw) of each herb crude extract was administered to the herb control group and 2-h previous to INH + RIF + PZA (AKT) doses to the Herb + AKT groups. Serum alanine aminotransferase (ALT), aspertate aminotransferase (AST) bilirubin and Alkaline Phosphatase (ALP) were assessed on d 0 and 21 in all the groups. Phagocytic % (P%), Phagocytic Index (PI) and Chemotactic Index (CI) were also measured as immunologic parameters. Histological analysis was carried out to assess injury to the liver. The AKT treated control group showed hepatotoxicity as judged by elevated serum AST 5-fold, AST/ALT ratio 4-fold, ALP 2-fold and hepatological changes, such as focal necrosis, portal triaditis and steatosis. Immune function was suppressed as judged by decreased P% (51.67 ± 1.68 vs 40.61 ± 1.28, P < 0.01), PI (2.0725 ± 0.05 vs 0.61 ± 0.05, P < 0.001) and CI (1.8525 ± 0.04 vs 0.695 ± 0.07, P < 0.001). All four herb treated groups showed normal liver histology, enzyme levels and increased P%, while PI and CI were enhanced in the TC and ZM treated groups, respectively. CL + AKT, TC + AKT and ZM + AKT showed nearly normal histology with minimal inflammation and microvesicular steatosis, while OS + AKT showed partial protection. Hepatotoxicity was prevented by restricting the rise of AST by 2-fold in CL + AKT and TC + AKT groups and by 3-fold in OS + AKT and ZM + AKT groups, AST/ALT by 2-fold and ALP to normal levels in all four groups. All four herb + AKT groups showed normal to enhanced neutrophil function. 

2. Phytochemical review

Gangan VD et al80 Several glycosides were isolated, as polyacetates, from the n-BuOH fraction of the Tinospora cordifolia stems. The structures of three new norditerpene furan glycosides cordifoliside A, B and C have been established by 1D and 2D NMR spectroscopy.

Jahfar M et al81 Polysaccharide from Tinospora cordifolia was isolated, purified, methylated, hydrolyzed, reduced and acetylated. The partially methylated alditol acetate (PMAA) derivative thus obtained was subjected to GC-MS studies. The following types of linkages were noticed: terminal-glucose, 4-xylose, 4-glucose, 4,6-glucose and 2,3,4,6-glucose.

Jahfar M et al82 Polysaccharide from Tinospora cordifolia was isolated, purified, hydrolysed, trimethylsilylated and then subjected to GC-MC studies. The polysaccharide composition was estimated as follows: glucose 98.0%, arabinose 0.5%, rhamnose 0.2%, xylose 0.8%, mannose 0.2% and galactose 0.3%.

Swaminathan K et al83(1S,4R,5R,8S,10R,12S)-4-Hydroxy-15,16-epoxycleroda-2,12(16),14- trieno-17,12: 18,1-biscarbolactone, C20H22O6, Mr = 358.2, m.p. = 453-454 K, orthorhombic, P2(1)2(1)2(1), a = 7.3869 (6), b = 11.986 (1), c = 19.896 (2) A, V = 1761.65 A3, Z = 4, Dx = 1.351, Dm(by flotation) = 1.349 g cm-3, lambda(Cu K alpha) = 1.5418 A, mu = 8.36 cm-1, F(000) = 760, T = 295 K, R = 0.0432 for 1662 observed reflections. Two terpene rings, two delta-lactones, two methyl groups, a tertiary hydroxyl group and a beta-substituted furan ring are present in the structure. The H atoms at C(12) and C(8) are alpha- and beta-oriented. The terpene ring A is locked into a boat conformation by the C(1)-C(4) lactone bridge. The furan ring is attached equatorially at atom C(12). The hydroxyl group is involved in intramolecular hydrogen bonding.

Swaminathan K et al84 (1S,2S,3R,4R,5R,8S,10R,12S)-4-Hydroxy-2,3:15,16-diepoxycleroda-13( 16),14- dieno-17,12:18,1-biscarbolactone, C20H22O7, Mr = 374, m.p. = 509-511 K, orthorhombic, P2(1)2(1)2(1), a = 9.191 (2), b = 13.8230 (6), c = 26.956 (2) A, V = 3424.50 A3, Z = 8, Dx = 1.450, Dm (by flotation) = 1.446 g cm-3, lambda (Cu K alpha) = 1.5418 A, mu = 8.20 cm-1, F(000) = 1584, T = 295 K, R = 0.0464, wR = 0.0579 for 3437 observed reflections. The asymmetric unit contains two molecules. The structure resembles that of a similar compound [Swaminathan, Sinha, Bhatt & Sabata (1988). Acta Cryst. C44, 1421-1424] with atom H(15) replacing the tertiary hydroxyl group at C(8). Atoms H(4) and H(15) are alpha- and beta-oriented respectively at sites C(12) and C(8). The terpene ring A is locked into a boat conformation by the C(1)-C(4) lactone bridge. The hydroxyl at C(4) is involved in hydrogen bonding.

3. SUMMARY

The literature survey of Tinospora cordifolia has shown the plant has several pharmacological activities. But it has prominent anti-diabetic activity, in terms of lowered levels of blood glucose and significantly increased levels of plasma insulin. The compound that have been isolated has shown 
 hepatoprotective activity against carbon tetrachloride (CCl4) induced toxicity
 immunomodulatory activities
Antioxidant activity that is due to an arabinogalactan polysaccharide (TSP) isolated from it.
When added to chloroquine (CQ) base (300 mg) shown anti-malarial activity
It give sthe antituberculosis treatment (ATT), when given for 90
It was found to be very effective in reducing the metastatic potential of B16F-10 melanoma cells.
It has shows an enhanced tumor cytotoxic activity. (inhibited the tumour directed capillary formation induced by melanoma cells)
The alcoholic extract of it gives cardioprotective activity.
It inhibits the lipid peroxidation and superoxide and hydroxyl radicals.
Anti-hyperglycemic effect of aqueous and alcoholic extracts as well as lyophilized powder of it.
intravenous administration of Tinospora cordifolia the formulation (5 mg/kg) gives anti atherogenic effect.

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