Tinospora cordifolia (GuducI)

Brihat Trayi texts mentioned it several times with important indications. Caraka quoted it among the Agrya dravyas (principal drugs) by attributing Grahi, vatahara, dipaniya, kapha-raktahara and vibandhahara properties to it (C.S.Su.25). He also Identified it as one of the the best medhya-rasayŒnas (brain tonics). Sushruta high-lighted the pitta-kaphahara properties of guduchi while Vagbhata  emphasized its utility in ‘vatarakta’. Among the laghu trayi, Sarnghdara stressed upon the utility of guduchi afresh.

Sushruta, Vagbhata and Bhavamishra described one complete Varga (group of drugs) in the name of Guduucyadi varga. He for the first time disclosed the mythological background/origin of Guduchi. According to him Guduchi story goes on like this: “During the fearsfull war between Rama and Ravana several monkey worriers were killed by the enemy forces. At the end, lord Indra sprinkled (Amrta) on their dead bodies and provided rebirth to the monkies. During the process where ever the drops have fallen on the ground, Guduchi plants originated”.

During the Nighantu period, the utility of Guduchi reached zenith and extensive description of Guduchi appears in all the nighantus. Some of the Yoga granthas have quoted  “in the absence of Guduchi sattva, the fresh juice may be used”. This concept is exactly opposite to the general principles laid down in the earlier texts.

The leaves of Guduchi are mostly described under the Saka varga and Tikta varga in the Ayurvedic texts.

Different Varieties–

In the original classical literature there is only one variety of Guduchi described. Dhanvantari Nighantu introduced two varieties of Guduchi for the first time. They are: Guduchi and Kandodbhava Guduchi. Gangadhara mentioned about ‘Padma Guduchi’ in his commentary (Ganga-C.S.Su.4). The botanical identity of second variety is Tinospora sinensis (Lour.) Merrill or T. malabarica.

Acharya P.V. Sharmaji reported that T. Crispa is being used in Assam for the management of fevers.

Classically, “Amrta dvaya’’ means Guduchi and Haritaki but not two varieties of Guduchi.

Botanical Descriptions–

• cordifolia Miers (Menispermum cordifolium Willd.)

It is a large climber with succulent, corky and grooved stems; branches possess slender pendulous fleshy roots. Leaves- membranous, glabrous, 5-10 cm long, cordate; petiole 2.5-7 cm long. Flowers- in racemes of about 5 cm; axillary, terminal or from the old wood, pale yellowish white in colour. Fruits- carpels, dorsally convex, ventrally flat, size of a large pea.

(ii) T. cinensis: (T. malabarica (Lam.) Miers).

It is a large climber with 2 cm diameter stem, old branches are smooth and shining, more or less warty light coloured papery bark, yong parts covered with whitish hairs. Leaves- membranous, sparingly pubescent above, broadly ovate-cordate, 7.5-23 cm long, petioles 6-12 cm. long, striate. Flowers- arranged in pseudo racemes arising from the old branches, simple, pedunculate, yellowish green coloured. Fruits- drupes 1-3, scarlet or orange coloured. Distribution– Both species are distributed almost throughout India. Cultivation– Propagated by cuttings of stem. It can be grown in almost any types of soil and under varying climatic conditions.

Chemical Constituents–

• Cordifolia– A diterpenoid of columbin type– tinosporin is isolated from plant (Sci. Cult. 26: p.140, 1960; Chem. Abstr. 61:12331 b, 1964). Tinosporide and cordifolide (Sci. Res. 1:177, 1964). Tinosporidine and β sitosterol isolated stems; cordifol, heptacosanol and octacosanol reported from the leaves (Comp. Ind. Med. Plants vol.2 p.679).

A new furanoid diterpene– tinosporide from stems (Ind.J. Chem; 16B:317, 1978 & Chem. Abstr. 93:72009c, 1980).

18-norclerodene glucosie– tinosporaside- from stem wood is reported (phytochem. 28:273, 1989 & Chem. Abstr. 112:211629; 1990).

Five diterpene furan glycosider, viz., cordifolisides A-E and two phenyl propane glycosides are isolated from aq. Extracts (Gangan et al; 1994).

Isocolumbin, tetrahydropalmatine, magnoflarine and palmatine were isolated from roots (Sarma et al;, 1998).

(ii) T. malabarica– sitosterol, tetracosanoic acid and tinosporin are reported (Ind. J. Chem. 20B: 834, 1981).

Tinosporinone and 5-allyloxy-6,7,4-trimethoxyflavone (phytochem. 21:2992, 1982).

Synthesis of 1,1-dibenoylethane (Ind. J.Chem. 22B:183, 1983).

Kokusaginine is reported (Planta Med. 51:529, 1985).

Malabarolide is isolated from the stem is a new bisnorditer penoid (Tetrahedron Lett., 29:4241, 1988).

Magnoflorine, quercetin-3-0-glucoside, kaemferol and its 3-0-glucoside from menispermicide are reported from stems (Phytochem. 31:3155, 1992).

New phenolic glycoside- tinosinen I is isolated from the fresh stems (Planta Med., 59:522, 1993).

Part used– Stem, leaf, areal roots.

Dose– Stem powder 3-6g; decotion (1/20) – 50-100ml; Infusion (1/10) – 30-60 ml; fresh juice 10-20ml; Guduchi Sattva 1-2g; DE 250-500mg (stem); TR (1/8) 2-8 ml.

Guduchi Sattva–

The process of ‘Sattva’ (cold water extract) is not traceable in the Brihat Trayi texts. It is mainly developed during the medieval period. The process involves, crusing of Guduchi stems and extracting in the cold water at room temperature (i.e.; without heating). After repeated extractions the cold-infusion is dried and the obtained solid powder is called as “Guduchi Sattva’.

It has been in extensive use in India as a valuable tonic, alterative and anti-pyretic. It caught the notice of Europeon physicians in Inida as a specific tonic, immune-modulatory and diuretic (Watt 1893; Pendse & Bhatt, 1932).

The drug itself as well as a tincture prepared from it are now official in the Indian pharmacopoeia.

The solid starchy extract is know by name Guduchi Sattvam, Giloi Ka Sat or Palo. Dr. Raghunathan K. is of the openion that the freshly prepard Guduchi Sattva is good in taste but carelessly prepared one is bitter. The sattwa obtained from the root is pure white, where as that obtained from stem may be slightly greyish to greenish.

According to Deshmukh et al.; (1957), Guduchi Sattva is cream coloured, bitter to taste having- starch grains, crystal fibres, vessel portions, parenchyma and cork cells.

Guduchi Sattva is claimed to be a potent tonic and immunomodulatory. It is useful in fevers, diarrhoea urinary tract infections, jaundice, skin diseases, irritable bowel syndrome and defects of semen morphology & spermatogenesis.

Pharmacological Studies–

2. It is found to be an effective anti-rheumatic and diuretic (Sisodia & Laxminarayan, 1966).

Rai & Gupta (1966) have carried out the experiments on the lithotriptic activity of T. Cordifolia. In 22 rats the stone formation was induced by implanting zinc pellets into the bladder. The deposition of the secondary salts over the zinc pellets was inhibited by the aqueous extract of T. Cordifolia.

2. The anti-inflammatory property is reported by Rai & Gupta (1966).

Water extract showed significant anti-inflammatory activity in rats against acute and chronic type of inflammation induced by carragenin and adjuvant (Pendse et al; 1980 & 1981).

3. It is reported to be one fifth potent as analgesic when compared to sodium salicylate.
4. Aqueous extract produced smooth muscle relaxation of intestines, uterus and inhibition of constrictor response of histamine and acetyl choline on smooth muscles (Gupta et al; 1967).

Aqueous extract of the stem was found to antagonize the effects of various agonists like histamine, 5H-T, bradykinin and prostaglandins E1 & E2 on the smooth muscles of guinea pig and rat (Singh et al; 1975).

5. Administration of aqueous extract (30days) showed significant improvement in the glucose tolerance in rats (Gupta et al; 1964).

Oral administration of the aqueous and alcoholic extract of the plant significantly reduced FBS in rabbits and rats. The bitter fraction of aqueous extract produced significant reduction in the blood sugar level, but it effectively inhibited the adrenaline- induced hyperglycaemia significantly (Gupta et al; 1967).

Its aqueous extract (stem) effectively reduced blood-sugar levels in the alloxan- induced hyperglycaemic rats and rabbits in a dose of 400gm/kg (Raghunathan & Sharma, 1968).

The anti-hyperglycaemic effect of aqueous and alcoholic extracts as well as lyophilized powder of T. cordifolia was evaluated in diabetic animals using different doses of diabetogenic agents for varying duration (21-120 days) so as to assess their effect in mild (plasma suger<180mg/dl, duration 21 days), moderated (plaswa sugar>280mg/dl, duration 120 days) and severe (plasma sugar>280gmldl, duration 60 days) DM. In the pilot study (mild diabetes), maximum reduction of 70.37% in glucose levels was seen in animals receiving 400mg/kg per day of aqueous extract after 3 and 15 weeks of treatment. The percentage reduction in glucose decreased significantly in the moderate and severe diabetics i.e.; 48.81% (Grover et al; 2000).

6. Hepatoprotective activity also reported. Conditions simulating viral hepatitis, fatty infiltration and cirrhosis were induced in rats by using CCl4in different doses and for variable durations and frequency. The acute liver damage was not prevented by T. cordifolia but the chronic damage was effectively prevented. It prevented the fibrous changes and promoted regeneration by parenchymal tissue (Rege et al; 1984a)

Aqueous suspension of the alcoholic extract of the stem provided protection to liver from injurious effects of CCl4 in mice, rats and rabbits. The protection is afforded also to the derangement induced by the chronic hepatotoxic effect of CCl4. Prevention of fibrosis by the plant might be by virtue of its action on immune process (Singh B. et al; 1984 a).

Kupffer cells are major determinants of outcome of liver injury. Their activity was therefore studied in a model of chronic liver disease in rats (N=24). The hepatoprotective activity of T. cordifolia was evaluated on Kupffer cell function, by using carbon clearance test as a parameter. The drug showed a significant improvement in ighant cell function (Deepa et al; 1994).

Hepato propective activity on CCl4– induced hepatotoxicity in Swiss albino mice is reported (Katewa & Arora, 2001).

7. The antioxidant activity of root extract (2-5 & 5g/kg for 6 weeks) is reported in alloxan diabetic rats (Prince P.S.M. et al; 1999).

Oral administration of 2.5gm and 5g/kg body weight of aqueous extract of roots for 6 weeks resulted in a significant reduction in thiobarbitonic acid reactive substances and on increase in reduced glutathione, catalase and superoxide dismutase in alloxan diasetic rats (Prince & Menon, 2001).

8. Administration of aqueous extract of roots (2.5 & 5g/kg for 6 weeks) significantly reduced the serum and tissue ighantuy, phospholipids and free-fatty acids in alloxan diabetic rats. The root extract (5g/kg) showed highest hypolipidemic effect (Prince et al; 1999).
9. Its aqueous extract has a high phagocytic index. The active constituent in the durg was also found to inhibit in vitro the growths of M. tuberculosis (Annual Report- ICMR, 1968-69; 1992 & Anon; 1976).
10. Ethanolic extract of stem and leaves exhibited significant antipyretic activity in experimental rats (Vedavathy & Rao, 1991).
11. Antiallergic properties of an aqueous extract of T. cordifolia stem on histamine induced bronchospasm in guinea pigs and experimental rats were evaluated. The extract significantly reduced the bronchospasm in guinea pigs, reduced the capillary permeability in mice and reduced the number of disrupted mast cells in rats (Nayanpalli et al., 1986).
12. T. cardifolia was found to be active against Leishmania donovani when administered to golden hamsters (Singha U.K. et al., 1992). Alcoholic extract is found to be effective against Esch. Coli (Gupta et al., 1967).
13. The efficacy of T. cordifolia was evaluated against E. coli-induced peritonitis in mice. Pretreatment with T. cordifolia (100mg/kg/day for 15 days; orally), produced leucocytosis with 26% mortality at 16 hrs, as against 100% in controlled animals. These results indicative of immunomodulatory properties of the drugs (Thatte U. et al; 1987).

The protective effect of pretreatment with T. cordifolia against mixed abdominal infection induced by ceacal ligation was studied in rats. The drug (20mg; 40mg & 100mg/kg body wt.) effectively reduced the mertality rate in a dose dependant manner. The results were comparable to that in the group given metronidazole and the infection and better sac formation. There was no increase in the peripheral neutrophil count and peritoneal macrophages which was associated with increased phagocytic activity of macrophages (Dhanukar et al; 1988).

14. The potentiality of T. cordifolia in cancer management is identified (Thatte U. et al; 1996).

Administration of stem methanolic extraet to BALB/C mice (200mg/kg, i.p. daily for 5 days) increased the total WBC count ighantuyy (p<0.001). It also increased bone-marrow cellularity and alpha-esterase positive cells in bone-marrow indicating increased malnutrition of stem cells. Administration of the extract also significantly raised humoral cells response, as seen from the increase in plaque- forming cells in the spleen and circulatory anti-body titre and to produce an enhancement in macrophage activation. The extract decreased the solid tumour growth and synergistically acted with cyclophosphamide in reducing (83%) the animal tumours.

15. 60 rats of Charles Foster strain weighing 200-250gm were used to study two formulations with T. cordifolia. There were 6 groups with 10 rats each. All animals feel for 15 days in prescribed doses after which they were subjected to cold immobilization stress. Subsequantly, Evans Blue was injected, 15 minutes, after injection animals were killed and stomach removed. The quality of Evans Blue in the stomach was established. Pretreatment with all plant products (including T. cordifolia) significantly reduced gastric damage (Till, 1994).

The alcoholic extract of roots was found to possess ighantuy the activity against stress-induced changes in norepinephrine (NE), dopamine (DA), 5- hydroxytryptamine (5-HT) and 5- hydroxyindoleacetic acid (5-HIA) levels in rats (Sarma D.N.K. et al; 1995).

Both T. cordiolia and C. asiatica (ethanol extraets) exhibited significant antistress activity (Sarma D.N.K., 1996).

16. T. cordifolia exhibited mild anti-ulcerogenic activity against gastric ulcers in rats (Biswas et al; 1993).

The ethanolic extracts of the roots of T. cordifolia and centella asiatica administered at a dose of 100mg/kg daily, were observed to induce a marked protective action against an 8 hour resistant stress induced ulceration. The activity was found to be comparable to that of diazepam in experimental albino rats. The antiulcer activity has been reported as a part of overall adaptogenic activity (Sarma, 1995).

17. I.V. administration of water extract in doses of 5,10 and 15mg/kg produced a marked but transient fall in B.P. along with bradycardia in the anaesthetized dogs. A decrease in thecoronary out flow in the isolated preparation of rabbit heart and above findings suggest that the basic action of the extract resembles with the cholinometric drugs. It significantly decreased blood urea levels in uremic dogs and patients (Singh et al. 1975).

Clinical Studies–

1. A clinical trial on 20 T.B. patients (2 months study) revealed that T. cordifolia lowered clincal composite score earlier than placebo, produced higher weight gain, reduced sputum conversion time, hastened radiological recovery offered better quality of life in early phase. Therefore the use of T. cordifolia as an adjuvant to anti-tubercular chemotherapy is justified (Rege D.A. et al; 2001).
2. Water extract of T. cordifolia was clinically evaluated in 50 patients of Amavata and Sandhigatavata. Out of these 48% got complete relief, 32% got partial relief and 20% showed some improvement (Mhaiskar V.B. et al; 1980). Clinical trial with a combination of Sunthi and Guduchi showed encouraging results (Kishore et al; 1980).
3. It has been observed that during the treatment with T. cordifolia, the frequency of asthmatic attacks has been considerably reduced in all asthmatics. There was also reduction in the severity of symptoms particularly cough and wheezing. Reducing the requirement of bronchodilators, including corticosteroids in noticed. Adjuvant treatment with T. cordifolia helps to maintain adequate pulmonary functioning in chronic asthmatics and maintain quality of life (Kulkarni, 1998).
4. Guduchi Sattwa was administered in a dose of 500mg three times a day to 40 patients suffering from fever. Relatively long term treatment of the patients was needed to get the best results (Kumar & Srivastava, 1995).
5. In a clinical trial Guduchi (powder 1-3gm t.d.s. and leaf juice 10 ml t.d.s.) was administered orally of for 15 days in 20 patients suffering from jaundice. The results showed significant improvement (Shyamsunder, 1976).
6. In other clinical trals its effection: Tvak rogas i.e., skin disorders (Dwivedi, 1989); Pandu i.e., anaemia (Meena R.R., 1994); Vatarakta i.e., arthritis (Balagangadhar, 1986 & Diwan, 1989); Medhya Rasayana effect i.e., brain tonic (Mehta, 1994 &Khara, 1983) etc., were studied and reported.