Indian Journal of Pharmacology 1994; 26: 1 -12

PERSPECTIVES

PROSPECTS AND PERSPECTIVES OF NATURAL PLANTS PRODUCTS IN MEDICINE

S.S. GUPTA
Pharmacology Research Unit C.D.R.S., 1965-83, Gandhi Medical College, Bhopal. Accepted for publication: February 14, 1994.

Summary

A vast majority of population particularly those living in villages depend largely on herbal medicines. Scientific data on a good number of medicinal plants investigated has been well documented. However, only very few drugs of plant origin could reach clinical use and the National Formulary could not adopt even a dozen of plant medicines. For this reason, a special effort is needed for development of herbal drugs having therapeutic utility. This article discusses in a broader perspectives several plants reported to have anti-asthmatic, antiallergic, anti-inflammatory, anti-atherosclerotic, antifertility, antidiabetic and antiviral effects. Herbal drugs traditional remedy perspectives

Key words

Man since time immemorial has been using herbs or plant products as medicine for developing immunity or resistance against cold, coryza, joint pains, fever etc. The traditional systems of medicines Ayurveda, Siddha and Unani are based on the experiences in the use of plant products in amelioration of common diseases. A vast majority of our population, particularly those living in villages depend largely on herbal remedies. A good number of herbal remedies have stood the test of time particularly for the treatment of allergic, metabolic and degenerative diseases associated with aging. However, no scientific data regarding their identity and effectiveness of these herbs was available except that in the treatise of Ayurveda and Unani medicine. In view of the above, pioneering research on indigenous medicinal plants was initiated by Sir Ram Nath Chopra, which is well documented in his comprehensive treatise. This inspired number of scientists to take up independent investigations on a number of medicinal plants, but due to lack of coordination their identity and effectiveness could not be authenticated. Therefore, integrated multi-disciplinary research on indigenous medicinal plants was sponsored under the Composite Drug Research Scheme by the Indian Council of Medical Research and later by the Central Council for Research in Ayurveda and Siddha at the regional science and medical institutions besides that being conducted in CSIR laboratories. Scientific data on a good number of medicinal plants investigated has been well documented.2-4 However, in spite of all these efforts, very few drugs of plant origin could reach Stage 1 of

clinical trial or could gain confidence for clinical use by the practitioners of modern medicine. Doubts have been raised for the use of herbal drugs on the reasons that (i) herbs of different origin are often known by the same popular name, (ii) plants growing in different climatic soil and seasonal conditions do not have identical chemical constituents or therapeutic effect, (iii) process of collection (fresh, shade or sun dried) extraction, processing and storage of herbal medicines cause variation in potency and safety, (iv) no specific standards for herbal medicines have been prescribed and (v) non availability of these herbal medicines in suitable dosageform createdifficulty in administration. These shortcomings have delayed the integration of some of the well recognised Ayurvedic or Unani recipes in the modern system of medicine. lnspite of several pitfalls encountered in the medicinal plant research, the prospects of development of indigenous drugs for health care delivery system should not be considered so bleak in view of the development of some drugs of promising therapeutic utility. This could be possible with the concerted efforts of team of phytochemists and pharmacologists working together in afew well organised laboratories for multi-dimensional chemical and pharmacological screening of the active fraction of the plants followed by the tests for specific activity such as anti-allergic, anti-inflammatory, hypolipidaemic, hypoglycaemic, hepatoprotective, adaptogenic, anti-fertility etc. Further detailed investigations on the mode of action have revealed their

Correspondence and Present address: Dr. S.S. Gupta, Professor of Pharmacology (Retd), Gulab Kutir, E-1138, Arera Colony. Bhopal - 462 016.

2 S.S. GUPTA

Table 1.

Percentage protection of guinea pigs on treatment with a few plant medicines on exposure to histamine and antigen (egg albumin) micro-aerosol. (Protection based on delay in onset of preconvulsive time and percentage calculated as per formula: -Xl 00. T Percentage protection on exposure to micro-aerosol

Treatment and Dose Histamine 2% Control saline 1 ml/ kg C. serratum saponin 10 mg/ kg G. turgida saponin 10 mg/ kg S.xanthocarpum saponin 20 mg/ kg Tylophora indica Alc. Extract 50 mg/ kg Curcuma longa Alc. Extract 50 mg/ kg 17.0 22.1 26.8

Antigen - egg albumin water suspension aerosol exposure at weekly intervals 1 27.2 44.9 47.5 2 33.6 66.6 70.3 70.0 3 38.4 79.5 81 .6 73.1

45.7 65.9 31 .8

30.5 43.7 46.5

*Preconvulsive time C before treatment and T after treatment with drugs. Data computed vide reference No.6

Figure 1. Isolated guinea pig ileum suspended in Tyrode bath. Constrictor responses of histamine (2 l(g) doses inhibited to more
than 50% height for longer period after the addition of lung extract from the treated group (lower panel) in comparison to inhibition caused by lung extract from untreated control animals (upper panel)

involvement In enzymatic, endocrinol, immunomodulating functions. These have helped to widen their profile of activity and opened new vistas of therapeutic applications. Amongst the several plants investigated for the antisaponins isolated from effects , asthmatic Clerodendron serratum 5, Gardenia turgida 6, Albizzia lebbeck 7 and Solanum xanthocarpum 6 were

found to accord protection to sensitised guinea pigs against histamine as well as antigen (egg albumin) micro-aerosols (Table 1). The protective effect of C.serratum saponin was found to be associated with the augmentation of anti-allergic activity in the lung tissues as the lung extracts from the treated animals inhibited histamine and SRS-Aresponses on guinea pig ileum to a greater extent and for longer period

NATURAL PLANTS PRODUCTS

Table 2.

Percentage disruption of rat mesenteric mast cells on challenge with antigen (horse serum). Degranulation (Mean- SE) of mas ceil percentage (reference in parenthesis)

Days of drug treatment

Control saline (mean) 71.90 * 5.60 74.60 * 7.09

C.serratum saponin A.lebbeck saponin

(14) 26.59 f 3.35 17.10 + 2.67

(15) 27.40 + 11.40 35.60 2 6.90

T.indica AlcExtract (17)

DSCG (17) 35.60 + 7.94

5- 12 l-10

38.80 e 1.1 I2

Figure 2. Guinea pig air insufflated isolated lung. Potentiation of bronchodilator response of isoprenaline (IP) after injection of T.indica alkaloidal fraction through the cannulated pulmonary artery perfused with Tyrode solution.

as compared to the extracts from untreated control animals (Figure 1). Saponin from Albizzia lebbeck has also been demonstrated to modulate immune responses through synthesis of reagenic antibodies9 The alcoholic extract of Tylophora indica (asthmaticus) has been reported to prevent egg albumin induced anaphylaxis in guinea pigslo and horse serum induced broncho-constriction in sensitised rat lung.v12 Further chewing of leaves of T.indica for 6 days has been demonstrated to give protection to 71% cases of bronchial asthma on antigen challenge. 1 3 The plant saponins from C.serraturn and A./ebbeck15 as well as the alkaloidal fraction of S.xan?hocarpuml 6 and T.indical 7 have been shown to protect sensitised mast cells from degranulation on antigen shock (Table 2) thus confirming the immuno- suppressive and membrane stabilising effect like sodium chromoglycate. Tindicala as well as saponins of A.lebbeck 19 and C.latifolia 20 have also been found to potentiate broncho-dilator beta-adrenergic activity which is considered to be helpful for relieving bronchospasm

in asthmatic patients (Figure 2). T.bellerica and Ocimum sanctum have also been demonstrated to give protection against histamine as well as pollen (Acacia arabica) induced bronchospasm in guinea pigs and the latter has also inhibited antigen induced histamine release from sensitised mast cells and gave relief in allergic bronchial asthmae21 The antiallergic action of O.sanctum has been found to be associated with significant production of IgE antibodies.22 Thus some of these plant medicines seem to be promising source for development of anti-asthmatic and anti- allergic drugs. A good number of plants having anti-inflammatory activity have been documented.2V3!23 The experimental data of some of these plants investigated in CDRS unit on various inflammatory models is compared in Table 3. It will be observed that Tinospora cordifolia ( b i t t e r principle)24, Balsamodendron mukul (olioresin) and Curcuma longa (volatile oil)*5 have significant anti-inflammatory activity as also confirmed by other workers.26-2s Both T.cordifolia and C.longa have also been found to

4 S.S. GUPTA

Table 3.

Anti-inflammatory and anti-arthritic effects of medicinal plants. Carrageenin oedema (ml) 0.537 + 0.051 24 * 25 38 43 ** 25 0.220 * 0.041 0.236 + 0.071 0.334 r 0.056 0.385 r 0.035 0.313 2 0.024 0.378 f 0.053 0.218 t 0.071 0.381 * 0.043 0.644 f 0.285 0.409 f 0.043 0.307 2 0.024 176.80 * 17.92 0.15 f 0.02 38.07 + 7.51 _ Formaldehyde Arth. swelling (ml) 0.930 f 0.331 0.261 + 0.021 0.451 f 0.140 0.331 2 0.056 _ 0.318 2 0.037 Fruends adjuvant arthritis (ml) 0.461 * 0.037 Granuloma pouch Weight (mg) 223.51 * 15.31 102.52 L 38.41 94.50 * 28.60 184.70 + 46.35 196.00 2 34.32 143.07 2 17.26 Exud (ml) 0.49 * 0.07 0.15 + 0.07 0.13 z 0.02 0.16 f 0.03 0.31 ? 0.06 0.23 f 0.13 54.26 - 8.41 47.90 -t 0.51 Cotton pellet weight (mg) 74.00 * 11.31 27.63 r 6.06 48.01 = 9.36

Treatment with Reference No. dose Control (saline) T. cordifolia (200 mg/ kg) B.mukul (200 mg/ kg) C.longa Vol.oil (0.1 ml/ kg S.rombofolia (100 mg/ kg) L.inermis (10 mg/ kg A.sativum Cortisone acetate (10 mg/ kg)

*M.D. Thesis - M.C. RAI, on Pharmacological evaluation of a few indigenous anti-arthritic and anti-inflammatory drugs-Tinospora cordifolia and Balsamodendron mukul, Bhopal University, 1967. **M.D. Thesis - N. MISHRA, on Anti-inflammatory and anti-arthritic effects of a few plant-volatile oil Curcuma longa and Allium sativum, Bhopal University 1972.

possess anti-allergic, mast cell stabilising effectszg130 and reported to be beneficial in cases of rheumatoid arthritis.31 32 Further the volatile oil of C.longa has also been found to inhibit and activated protease@ss hyaluronidase33 responsible for acute inflammatory process, while curcumin, the other active constituent of C.longa, inhibits prostaglandin synthesis.34 All these effects are likely to add to its anti-inflammatory activity which is reported to be comparable to phenylbutazone.32 Alcoholic extract of Boswellia serrata (salai guggul)ss has also been reported to display prominent anti-arthritis activity by inhibiting adjuvant induced arthritis and the inflammatory rise of SGPT and SGOT in rats. The effect was comparable to phenylbutazone. In a double blind clinical trial, an Ayurvedic formulation containing Curcuma longa, Withania somnifera with Boswellia serrata has been claimed to significantly reduce severity of pain, morning stiffness, Ritche articular and disability score in cases of rheumatoid arthritis.36 The anti-inflammatory activity of Withania somnifera37 like Sida rhombifolias8, though moderate, is associated with reduction in spasticity of joints besides anti-ulcerogenic3g and other adaptogenic properties. Both Gossypin40 isolated from Hibiscus vitifoleus and the petroleum ether extract of Ricinus cornrn~rti~~ have more

significant anti-inflammatory activity against various phlogistic agents and adjuvant induced arthritis, being more effective than phenylbutazone in suppressing the acute as well as late phases of inflammatory oedema and protein extravasation.40 The milk extract of Semicarps anacardium though claimed to be highly beneficial in cases of rheumatoid arthritis (Charak) could only suppress the acute inflammatory oedema, but not the secondary lesions associated with adjuvant arthritis.42 Lawsonia inermid3, (with lawsone as active principle44) and Embelia ribe.@ have been found to possess potent anti-inflammatory, analgesic and anti-pyretic activity useful for relieving the misery of rheumatoid arthritic patients. Thus some of these plant medicines have potentiality of being good substitutes to non steroidal anti-inflammatory drugs without having untoward effects of gastric acidity or ulceration. Search for a potent hypolipidaemic agent based on ancient in sight on Ayurveda, has been rewarding with isolation of olioresin fraction from Commiphora mukuP6 and development Gugglipid47 having hypolipidaemic activity comparable to clofibrate with more favourable HDL and LDL cholesterol ratio on clinical trials.48 It also decreases platelet adhesive-

NATURAL PLANT5 PRODUCT5

Table 4.

Comparison of average percentage change in blood sugar in control and drug treated rats administered anterior pituitary extract (100 mg/ kg) subcutaneously and glucose (50% 2 ml/l 00 gm) orally. Average percentage of blood sugar (mg/100 ml) in reference to 100 percent pretreatment level at the following intervals Initial 100 100 100 100 100 100 3h 120.2 91.7 111.3 111.4 111.3 121.7 6h 137.5 69.1 121.6 115.2 106.7 109.9 12 h 164.3 135.7 151.5 136.9 133.5 116.9 24 h 162.3 122.9 143.6 133.2 131.5 120.3

Group

Drugs with dosage Solvent (control) G.sylvestre (100 mg/ kg) C. in dica 100 mgi kg
P.marsupium

I II III IV V VI

20 ml/ kg
M. charantia

5 ml/ kg Tolbutamide 50 mg/ kg

ness and increases fibrinolytic activity necessary for prevention of myocardial infarction. Hypolipidaemic and cardio protective effect of C.mukul in combination with Terminalia arjun and Inula racemosa, comparable to Gemfebrozil have also been reported.49 Salai guggul from Boswellia serrafa roxb has been shown to significantly affect the biosynthesis of cholesterol in rat liver.50 Further, hypocholesterolaemic effect of Pterocarpus marsupiun25l associated with hypoglycaemic activity is of a clinical significance as hypercholesterolaemia is often associated with diabetes. In view of the putative linkage of serum cholesterol with atheroscelerosis, dietary manipulation has clinical importance. Plumagin, napthaquinone derivative, isolated from Plumbago zeylanica has been reported to significantly reduce serum cholesterol together with LDL-C in hyperlipidaemic rabbits and also regress atheromatous plaques in the ateries.52 Likewise Allium sativum (garlic), Allium cepa (onion) besides influencing the lipid metabolism prevent atherosclerosis53 and isoprenaline induced myocardial necrosis54 with prolongation of bleeding and clotting time.55 Turmeric (haldi) and its derivative curcumin besides lowering the serum cholesterol and blood sugar level56 also acts as anti-oxidant to prevent peroxides to serum scavenge atherosclerotic changes. 57 The common vegetable Trichosanthus dioca (parval)58 and Gyamposes tetragoloba (guar)5g and some plant sterols lower blood cholesterol level by interfering with absorption and synthesis. The hypolipidaemic effect of these common food substances is in conformity with Hippocrates concept let food be your medicine.

Medicinal plants commonly included in Ayurvedic recipes for liver ailments have drawn much attention as no reliable hepato-protective drug is available in modern medicine. Research investigations conducted on several natural plant products used as liver protectives is well documented.60 Hepatoprotective effect of some of these like Picrorhiza kurroa 61 Tinospora cordifolla 62, Withania somniferas3, Ricinis communis64, Tephrosia purpurea65 against carbon tetrachloride and galactosamine induced hepatic injury have been confirmed experimentally by various workers. As regards the plant products for biliary ailments, A n d r o g r a p h i s paniculatass, Luffa echinatg7 and Ficus hispidg8 have been found to increase bile flow with reduction in serum bilirubin and SGPT level. Choleretic and anti-cholestatic activity of picroliv isolated from P.kurroa against thioacetamide induced cholestasis in guinea pigs has been reported.69 Phyllanthus niruri and Eclipta alba have been reported to inactivate hepatitis surface B antigen for effective treatment of hepatitis.70 Search for liver protectives has been a promising field of investigations and number of formulations containing some of these plant products are being routinely used for hepatic disorders. Plant products investigated for anti-diabetic effect have been exhaustively reviewed,71-73 and the inhibitory effect of some of the common plant extracts against hyperglycaemic response of anterior pituitary extract in glucose fed rats has been compared in Table 4. It will be observed that some of the plant extracts restrict the rise of blood sugar caused by the pituitary hormones responsible for inhibiting peripheral utilisation of glucose as well as causing glycogenolysis in maturity onset diabetes.

6 S.S. GUPTA

Table 5.

Effect of chronic treatment with with insulin)

Casearia esculenta

on glucose uptake by rat tissues (diaphragm pieces on incubation

Glucose uptake mg per 100 mg wet tissue Treatment for 15 days with Tissue blank control Untreated + Insulin 0.01 II/ ml 0.367 -c 0.097 Treated + insulin 0.01 n/ml 0.425 + 0.068 Untreated + Insulin 0.02 n/ml 0.466 r 0.057 Treated + insulin 0.02 p/ml 0.528 2 0.133

C.esculenta aqueous extract 200 mg/ kg Root pulv 200 mg/ 100 gm diet

0.253 z 0.036 0.199 r 0.201

0.354 + 0.242

0.492 t 0.245

0.496 L 0.068

0.685 -c 0.218

Data reproduced from research paper reference No.83

In this regard the leaf extract of Gymnema sylvestre with its constituent gymnemic acid by inhibiting the stress responses mediated through the adrenohypophyseal axis74 as well as the hyperglycaemic response to adrenaline,75 corticotropin and somatotropin76 may help in unrestricted utilisation of glucose by the peripheral tissues. Tinospora cordifolia has been found to inhibit hepatic glucose release caused by adrenaline,77 while Coccinia indica, Casearia esculenta and Pterocarpus marsupium besides reducing blood sugar have also been reported to block glucose absorption from the gut.78879 A flavanoid-epicatechin isolated from P.marsupium has been reported to promote regeneration of Beta cells of Langerhans in pancreasso and on clinical trials beneficial effects have been reported in maturity onset diabetes.81 T i n o s p o r a cordifolia82 and Casearia esculenta83 have been observed to promote insulin induced glucose uptake by the tissues (Table 5) and improve glucose tolerance,84 while Momordica charantia Linn also promoted peripheral utilisation of glucose.85 Further, fresh juice of M.charantia has been reported to potentiate tolbutamide actions6 and a crystalline fraction isolated from fruits of this plant has been reported to cause hypoglycaemic effect similar to insulin in juvenile diabetes.87 The antidiabetic effect of shilajit and Ficus bengalensis (milk sap) have been found to be associated with their weight promoting, anabolic and pancreatrophic effects.s878s These plant products are considered to act as biocatalystso to increase the peripheral demand of glucose for the growth and metabolic process similar to that effected by somatotropinsl and may promote weight gain in juvenile lean diabetics. Thus the plant medicines by inhibiting the vicious cycle of hyperglycaemia seem to save the beta cells in pancreas from deterioration by restricting glucose loads2 and also by promoting unrestricted endogenous insulin action. Thus these

herbal remedies can act as good adjuvant drugs to reduce the requirement of insulin or sulphonyl urea derivatives. This, however, is required to be confirmed through controlled clinical trials. Research on plants for fertility control aimed at interception in the process of ovulation, fertilisation and implantation through strategic approachesss-9s has been exhaustively reviewed.ss-9s Saponin of Albizzia lebbeck and ethanol extract of R a n d i a dumetorum have been shown to inhibit copper acetate induced ovulation mediated through central neurohormonal mechanismsgg Plant extracts from Aristolochia indical 00, Vitex negundolol , Randia dumetoruml02 with their anti-estrogenic activity intercept in the process of synchronised development of ovum and the endometrium, while some of these plants like Curcuma longa, Embelia ribes, Mentha avensis also render the endometrium or decidua unresponsive to implantation of the fertilised ovum or the embryo due to their anti-inflammatory activity associated with inhibition of prostaglandin synthesis and immuno-suppressive activity.103 Immunological mechanism similar to homograft rejection reaction involving the liberation of histamine (for vascularisation) have been postulated during implantation of human egg.104 This seems to be well substantiated by our observation that endometrial tissues obtained from sterile women were less responsive to histamine release induced by dextran or compound 48/80 and such endometrial tissues were also found to be deficient in histamine content as compared to the tissues obtained from fertile women.105l106 Plants like A.lebbeck and O.sanctum which have immuno-suppressive effects have been found to have anti-implantation effect.07 Further as the blastocyst implantation also involves trypsin or chymotrypsin like proteolytic enzymes in shedding of zona pellucida, trypsin inhibition activity as present in Curcuma longs3, Lawsonia inermH3, Solanum nigram, Pisum sativum, soyabean etc.,

NATURAL PLANTS PRODUCTS

may also affect the implantation process.lcs Thus Centchroman by producing asynchrony between ovum transport and uterine preparation for reception without affecting the hypothalmo-pituitary ovarian axis has come out as successful oral contraceptive. This has further shown how the biological effects of natural plant products can be utilised for fertilised regulation. Adaptogenic drugs which help to develop resistance against diseases, endurance against stress and retard aging process besides giving a feeling of well being, are well recognised in Ayurvedic medicine. Lately, these have gained much popularity all over the world. The anti-stress plant drugs as tested on biological parameters like swimming endurance, adrenal function tests, anti-ulcer activity etc. have been reviewed. 0,11 1 Antistress activity of 0.sanctum1r2 has been found to be significantly more than Eleutherococcus senticosus (Siberian ginseng) and Panax ginseng (Chinese ginseng) which have been in greater demand in rich countries. Ginseng contains number of saponins (terpine glycosides) claimed to enhance natural resistance and recuperative powers of the body. In this regard, Withania somniferall3 and Borrhavia diffusa (Punernava)14 have also been found to enhance survival during stress and increase body weight and haemoglobin besides influencing the aging process115 Similarly, Diospyros peregrina (Gurke) has also been reported to cause greater tolerance to anoxic stress and inhibit stress as well as aspirin induced ulcers, adrenal ascorbate depletion and improve swimming performance in adrenalectomised mice.116 The antistress profile of D.peregrina is considered similar to ginseng. Development of body resistance or immunity against infection has also been reported after treatment with Abutilon indicum (Atibala) and Sida cardifolia (bala) as evidenced by enhanced production of anti-S.typhi 0 antibody _ and protection against tissue damage.ll7Thus some of these plant products seem to activate body defence mechanism to fight against the disease. Plants have also been source for development of anti-cancer compounds and anti-viral interferons.lls An interferon stimulator (SNMC) derived from Glycerrhiza glabra has been reported to give protection to patients of subacute hepatic failure known to be fatal in majority of cases.11g Successful treatment of subacute hepatic failure with interferon stimulator brings into focus the trial for many other indigenous drugs for the treatment of viral hepatitis and many other similar diseases including cancer. Possibility of development of a herbal drug for treatment of auto-immune diseases like multiple

scelerosis and the most dreaded disease AIDS cannot be ruled out. In a broader perspective, plants are not only economic source of a number of important drugs like morphine, atropine, digoxin etc., they are also source of chemical intermediates for production of cortical hormones, oral contraceptives and anabolic drugs from steroidal sapogenins extracted initially from Dioscorea deltoida and later from D.floribunda and D.composita and other hybrid varieties as former species got extinct. The perpetual biodiversity in nature will continue to provide newer species of plants for getting variety of chemicals for production of newer drugs. However, species of plants yielding better quantity of the desired chemicals as active principles can be developed through genetic engineering while their production can be accelerated through tissue culture techniques.lzO Thus from the foregoing, it will be observed that plants have vast potential to biosynthesis chemicals (active principles) during adaptation to environment stress and this source should be exploited to get useful medicines to fight against diseases. Plant remedies in natural form act slowly but have more lasting effect with little or no untoward effects as the different constituents in the plant compensate for each other action. It is, however, necessary to process the plant to get desired effect in the minimum dosage form. To meet this objective judicious efforts are required in selection of plant material, time for its collection, method of processing and pharmacological screening for proper therapeutic effects, It should also be realised that some plant medicines act directly on the living system while others act indirectly to modulate endocrine or autocoid systems to help in adaptation to environment (milieu exterior), or induce immune system to produce antibodies, opsonins and interferon like substances for body defence. The adaptogenic plant medicines from O.sanctum, Withania somnifera, Abutilon indicum which impart immunity or body resistance as well as interferon inducers from Glycyrrhiza glabra have given new direction for the treatment of many intractable viral, autoimmune and degenerative diseases. Immunomodulatory effects of Tylophora indica and Albizzia lebbeck with bronchodilator effect provides a suitable anti- asthmatic drug with no side effects and the latter also having the advantage of being free from risk of atherosclerosis121 in view of its hypolipidaemic effect. Hyperlipidaemia and associated risk of atherosclerosis can be effectively managed with Gugglipid isolated from C.mukul as it influences more favourable HDL cholesterol ratio for cardioproductive effects. Similarly, picroliv from

8 S.S. GUPTA

P.Kurroa and many other plants have been found to have significant hepato-protective and choleretic effect for the management of hepatic disorders, The anti-inflammatory effect associated with many beneficial biological activities in a number of m e d i c i n a l p l a n t s - C.longa, H.vitifoleus, R.communis, W.somnifera etc. can be utilised for the development of a potent drug for the treatment of rheumatoid arthritis. Anti-diabetic plant remedies G,.sylvestre, P.marsupium, T.cordifolia etc. by breaking the vicious cycle of hyperglycaemia and promoting unrestricted insulin action provide good adjuvant drugs for diabetes as they save further deterioration of the pancreatic lesion. Possibility of even regeneration of beta cells can be considered if claim for this noval activity of P.marsupium b e c o n f i r m e d . Development of Centchroman from rhisomes of C.longa has shown how the multiple biological activity present in the plant can be utilised for fertility regulation which is very much needed in our country. The objective of producing inexpensive, potent and safer drugs of plant origin can be met to some extent by promoting compound formulations of plant medicines in their natural or semi-processed form

(powder or extracts) as used in traditional medicine for common disorders. Proper standardization and dosage formulation in due consideration of the therapeutic and toxicity ratio will however be necessaryfor controlled clinical trials to prove their efficacy. Development of a single drug based on the active principle can also be taken up to rationalise drug therapy as well as to develop synthetic analogues on their model for specific activity. Research on medicinal plants in each geographical region need to be conducted for proper integration of these remedies in the modern system of medicine for providing benefit of effective and cheaper drugs from the right plant resource available in our vast country. ACKNOWLEDGEMENTS The author is grateful to the Indian Council of Medical Research and the Central Council for Research in Ayurveda and Siddha for providing grant-in-aid under the Composite Drug Research Scheme to carry out investigations on the indigenous drugs. He is also thankful to other colleagues who had collaborated in these investigations.

REFERENCES
1. Chopra RN, Chopra IC, Handa KL, Kapur LD. Chopras indigenous drugs of India. Calcutta: U.N. Dhar & Sons Pvt. Ltd., 1958. 2. Satyavati GV, Raina MK, Sharma M. Medicinal plants of India, Vol.l. New Delhi: Indian Council of Medical Research, 1976. 3. Satyavati GV, Gupta A, Tandon N. Medicinal plants of India, Vol.ll, New Delhi: Indian Council of Medical Research, 1987. 4. Monograph on pharmacological investigations of certain medicinal plants and compound formulation used in Ayurveda and Siddha, Pub. Central Council for Research in Ayurveda and Siddha (Ministry of Health and Family Welfare, Delhi: 1982. 5. Gupta SS. Development of antihistamine and antiallergic activity after prolonged administration of a plant saponin from Clerodendron serratum. J Pharm Pharmac 1968;20: 801-2. 6. Gupta SS. Indigenous drugs in experimental bronchial asthma. Aspect Aller Appl lmmunol 1971;5:31-42. 7. Tripathi RM, Das PK. Studies on antiasthmatic and antianaphylactic activity of Albizzia lebbeck. Indian J Pharmacol 1977;9:189-194. 8. Gupta SS, Modh PR, Ram AK. Development of anti-allergic and anti- histamine activity in relation to histamine releasing effects of plant saponin from Clerodendron serratum. Aspect Allergy Appl lmmunol 1968;3:133-42. 9. Tripathi RM, Sen PC, Das PK. Further studies on the mechanism of the anti-anaphylactic action of Albizzia lebbeck - an Indian indigenous drug. J Ethanopharmacol 1979;1:397-406. 10. Harnath PSRK, Shamla Kumari S. Experimental study in the mode of action of Tylophora asthmatica in bronchial asthma. Indian J Med Res 1975;63:661-8. 11. Gupta SS. Pharmacological basis for the use of Tylaophora indica in bronchial asthma. Aspect Aller Appl lmmunol 1975;8:95-100. 12 Nayampalli S, Sheth UK. Evaluation of anti-allergic activity of Tylophora indica using rat lung perfusion. Indian J Pharmacol 1979;11:229-32. Shivpuri DN, Agarwal MK. Further studies on the effect of Tylophora indica leaves on bronchial sensitivity to inhalation challenge with specific antigen in 31 asthma patients. Aspect Aller Appl lmmunol 1971;5:43-56. Gupta SS, Tripathi RM. Effect of chronic treatment of the saponin of Clerodendron serratum on the disruption of mesenteric mast cells. Aspect Aller Appl lmmunol 1973; 4:177-88.

13

14

NATURAL PLANTS PRODUCTS

15. Tripathi RM, Sen PC, Das PK. Studies on the mechanism of action of Albizzia lebbeck an indigenous drug used in the treatment of atopic allergy. J Ethanopharmacol 1978; 1:385-96. 16. Chitravanshi VC, Gupta PP, Kulshrestha DK. Kar K, Dhawan BN. Anti-allergic activity of Solanum xanthocarpum. Indian J Pharmacol 1990:22:23. Geetha VS, Viswanathan S, Kameswaran L. Comparison of total alkaloids of Tylophora indica a n d d i s o d i u m chromoglycate on mast cell stabilisation Indian J Pharmacol 1981;13:199-201. Gupta SS, Tripathi RM. Experimental studies on Tylophora indica. Aspect Aller Appl lmmunol 1973;6:93-9. Tripathi RM, Biswas M, Das PK. General pharmacological studies of Albizzia lebbeck. J Res Indian Med Yoga and Homoeo 1977;4:198-203. Gupta SS. Some observations on the anti-asthmatic effect of the saponin of Gardenia latifolia. Aspect Aller Appl Immunol 1974;7:198-204. Palit G, Singh SP, Singh N, Kohli RP, Bhargava KP. An experimental evaluation of anti-asthmatic plant drugs from ancient Ayurvedic medicine. Aspect Aller Appl lmmunol 1983;16:36-41. Sen P. Therapeutic potential of Tulsi (Ocimum sanctum) from experience to fact. Drugs News and Views 1993; 1:15-8 Handa SS, Chawla AS, Sharma AK. Plants with anti-inflammatory activity. Fitoterapra 1992;63:31,

31. Kishre P, Pandey PN, Rohit SD. Role of Sunithi Guduchi in treatment of Amavat-Rheumatoid arthritis, J Res Ayur Siddha 1980;1:417-28. 32. Deodhar SD, Sethi R, Srimal RC. Preliminary studies on anti- rheumatic activity of Curcumin (diferolyl methane). Indian J Med Res 1980:74:632. 33. Tripathi RM, Gupta SS, Chandra D. Anti-trypsin and antihyaluronidase activity of the volatile oil of Curcuma longa (Haldi). Indian J Pharmacol 1973;5:260. 34. Shrivastava R, Puri V, Srimal RC, Dhawan BN. Effect of Curcumin on platlet aggregation and vascular prostacyclin synthesis-Arzneim. Forsch 1986:36:715. 35. Zutsi U, Dhar SK, Johri RK, Gupta S, Sarin YK. New utilisation of some indigenous drugs. In: Dandiya PC, Vohora SB, eds. Research and Development of indigenous drugs. Institute of History of Medicine and Medical Research. New Delhi: 1989:186. 36. Kulkarni RR, Patki PS, Jog VP, Gandage, Patwardhan B. Efficiency of an Ayurvedicformulation in rheumatoid arthritis - a double blind placebo controlled cross over study. Indian J Pharmacol 1992:24:98-l 01. 37. Singh N, Nath R, Agarwal AK, Kohli RP. A pharmacological investigation of some indigenous drugs of plant origin for evaluation of their anti-pyretic, analgesis and anti-inflammatory activities. J Res Indian Med Yoga and Homoeo 1978;13:58-62.

17.

18.

19.

20.

21.

22.

23.

38. Gupta SS, Bhardwaj OP, Shrivastava V. Anti-inflammatory and adrenergic effects of Sida rhombofolia (Mahabala). Indian J Pharmacol 1979;11:40. 39. Sahni YP, Parasar GC, Srivastava DN. Anti-ulcerogenic effect of Withania somnifera on aspirin induced gastric ulcers. Indian J Pharmacol 1990;22:7. 40. Parmar NS, Ghosh MN. Comparative effects of Gossypin and phenylbutazone on the temporal characterisation of carrageenin induced paw oedema and increased vascular permeability in rat. Indian J Pharmacol 1980;12:201, 41. Banerjee S, Bandyopadhyay SK, Mukerjee PK, Mukerjee A, Sikdar S. Further studies on the anti-inflammatory activity of Ricinus communis in albino rats. Indian J Pharmacol 1991;23:149-52. 42. Satyavati GV, Prasad DN, Das PK, Singh HD. Anti-inflammatory activity of Semicarpus anacardium Linn. a preliminary study. Indian J Physiol and Pharmacol 1969;13:37-45. 4 3 . G u p t a S , G u p t a S S . A n t i - i n f l a m m a t o r y a n d antihyaluronidase activity of Lawsonia inermis. Proceedings of Decineal Conference of Indian Pharmacological Society, Calcutta, December 1977. Abstracts. Indian J Pharmacol 1978;10:90. 44. Gupta A, Saifi AQ, Modi NT, Rao SS, Mishra N. Anti-inflammatory activity of active principles of Lawsonia inermis leaves. Indian J Pharmacol 1990;22:27.

24. Gupta SS, Shrivastava MC. Anti-inflammatory studies of Tinispora cordifolia (Gudichi). Indian J Pharmacol 1966: 6:12. 25. Chandra D, Gupta SS. Anti-inflammatory and anti-arthritic activity of the volatile oil of Curcuma longa (Haldi). Indian J Med Res 1972;60:138-42. 26. Pendse VK, Mahavir MM, Khanna KC, Somani SK. Anti-inflammatory and related activity of Tinospora cordifolia (Neem giloe). Indian Drugs 1981 ;19:14-71. Gujral ML, SareenK, Amma MVP, Ray AK. Anti-arthritic and anti- inflammatory activity of Gum guggul. Indian J Physiol and Pharmacol 1960:4:267-73.

27.

28. Srimal RC, Dhawan BN. Pharmacology and diferloyl methane (Curcumin) a non-steroidal anti-inflammatory agent. J Pharm Pharmacol 1973;25:447. 29. Nayampalli S, Desai NK, Ainapure. Anti-allergic properties of Tinospora cordifolia in animal models. Indian J Pharmacol 1986;18:250-2. 30. Gupta SS, Modh PR. Anti-inflammatory effect of C u r c u m a longa in relation to inhibition of histamine release and mast cells. Indian J Pharmacol 1969;1:22.

10

S.S. GUPTA

45.

Gupta OP, MMohdAli, Ray Ghatak BJ, Atal CK. Some pharmacological investigations of embelin and some of its synthetic derivatives. Indian J Physiol and Pharmacol 1977:21:31-9. 60.

caemic and hypolipaemic effect of G y a m p o s i s a n d tetragonoloba (Guar) in normal and diabetic guinea pigs. Indian J Physiol and Pharmacol 1987;31:77-83. Handa SS, Sharma A, Chakravarti KK. Natural products and plants as liver protectives drugs. Fitoterapia 1966; 57:307. Pandey VN, Chaturvedi GN. Effect of alcoholic extract of kutki (Picrorhiza kurroa) o n e x p e r i m e n t a l l y i n d u c e d abnormalities in liver of rabbit. J Res Indian Med 1968:3:25. Singh B, Sharma ML, Gupta JK, Atal CK, Arya PK. Protective effect of Tinospora cordifolia mier on carbon tetrachloride induced hepato-toxicity. Indian J Pharmacol 1984;16: 139-42. Sudhir S, Budhiraja RD. Protective effect of withferin against an experimental model of hepatitis. Indian J Pharmacol 1991 ;23:16. Agarwal SS, Asnani RK. Hepatoprotective activity of indigenous plants. In: Dandiya PC, VohoraSB, eds. Research and Development of indigenous drugs. New Delhi: Institute of History of Medicine and Medical Research, 1969:152. Ramamurthy SM, Srinivasan M. Hepatoprotective effect of Tephrosia purpurea in experimental animals. Indian J Pharmacol 1993:25:34-8. Chaudhury SK. Influence of Andrographis paniculata (Kalmegh) on bile flow and hexobarbitone sleeping time in experimental animals. Indian J Exp Biol 1978;16:830. Vaidya AB, Bhatia CK, Mehta JM, Sheth UK. Therapeutic potential of Luffa echinafa Roxb in viral hepatitis. Indian J Pharmacol 1976:6:245. Gupta SS, Sharma SK. Choleretic and lactogenic activity of Ficus hispida. ( A b s t ) P r o c e e d i n g s o f A s i a n C o n g Pharmacology, New Delhi 1965;1-155. Shukla B, Visen PKS, Patnaik GK, Dhawan BN. Choleretic and anti- cholestatic activity of picroliv against thioacetamide induced cholestasis. Indian J Pharmacol 1991 ;76:124. Thyagarajan SP, Thiruneelakantan K, Subramanian S, Sundaravelu. In vitro inactivation of Hbs.Ag by Eclipta albaHasekand Phyllanthus neruri Linn. Indian J Med Res 1982; 76:124. Aiman R. Recent research in indigenous anti-diabetic medicinal plants an overall assessment. Indian J Physiol and Pharmacol 1970;14:65-76. Handa SS, Chawla AS, Maninder. Hypoglycaemic A review. Fitoterapia 1989;60:195. plants:

46. Satyavati GV. Gum guggul (Commiphora mukul)- the success story of an ancient insight leading to a modern dis covery. Indian J Med Res 1988;87:327-35. 61.

47. Nityanand S, Kapur NK. Cholesterol lowering activity of

various fractions of guggul. Indian J Exp Biol 1973;11:395.

48. Malhotra SC, Ahuja MMS, Sundarum KP. Long term clinical
studies on hypolipidaemic effect of Commiphora mukul (gugglu). Indian J Med Res 1977;65:390-5.

62.

49. Banerjee S, Bandyopadhyay SK, Mukerjee PK, Mukerjee

NK, Chowdhury S, Mukerjee A. Clinical studies on hypolipidaemic and cardioprotective effect of some indigenous drugs. Indian J Pharmacol 1993;25:47. 50. Zutsi U, Rao PG, Kaur S, Singh GB, Singh S, Atal CK. Mechanism of cholesterol lowering effect of Salai guggul Ex. Boswellia serrata roxb. Indian J Pharmacol 1986;13: i 82-3. Pandey MC, Sharma PV. Hypocholesterolaemic effect of bark of pterocarpus marsupium roxb (Bijaka) - an experimental study. J Res Indian Med Yoga and Homoeo 1978;13:6. Sharma Indu, Gusain D, Dixit VP. Hypolipidaemic and antiatheroscelerotic effect of plumagin in rabbits. Indian J Physiol and Pharmacol 1990;35:1 O-l 4. 67. 53. Kumar A, Bhasin B, Kulshrestha VK, Arora SR, Prasad DN. Comparative study of anti-atheroscelerotic activity of Allium cepa and Allium sativum and Commiphora mukul in rat and rabbit. Indian J Pharmacol 1979;11:61. Saxena KK, Gupta B, Kulshrestha VK, Shrivastava RK, Prasad DN. Effect of garlic pretreatment on isoprenaline induced myocardial necrosis in albino rats. Indian J Physiol and Pharmacol 1980;24:233. Bordia A, Bansal MC, Arora SK, Rathore AS, Ranavat RVS, Singh SV. Effect of essential oil of garlic on serum cholesterol, plasma fibrinogen, whole blood clotting time and firbinolytic activity in alimentary lipaemia. J Assoc Physicians India 1974;22:267-70. Shinde S, Rao SS. Blood glucose lowering potential of Curcuma longa. Indian J Pharmacol 1991;23:31. Soni KB, Kuttan R. Effect of oral curcumin administration on serum peroxides and cholesterol levels in human volunteers Indian J Physiol and Pharmacol 1992;36:273-5. Sharma G, Pant MC. Effect of raw deseed fruit powder of Trichosanthus dioca roxb on blood sugar, serum cholesterol, high density lipoproteins, phospholipids and triglyceride level in normal rabbit. Indian J Physiol and Pharmacol 1988;32:1 61-3. Shrivastava A, Longia GS, Singh SP. Joshi LD. Hypogly63.

64.

51.

65.

66. 52.

68.

54.

69.

55.

70.

56.

71.

57.

72.

58.

73.

lvorra MD, Paya M, Villar A. A review of natural products and plants as potential anti-diabetic drugs. J Ethanopharmacol 1989;27:243. Gupta SS, Variyar MC. inhibitory effect of Gymnema sylvestre (Gurmar) on adreno-hypophyseal activity in rats. Indian J Med Sci 1961 ;15:656-9.

74.

59.

NATURAL PLANTS PRODUCTS

11

75. Gupta SS. Inhibitory effect of Gymnema sylvestre on adrenaline induced hyperglycaemia 1961 ;15:833. in rats. Indian J Med Sci

extract on glucose tolerance in rats. Indian J Med Res 1966;54:354-62. 90. Ghosal S. The facet and facts of Shilajit. In: Dandiya PC, Vohora SB, eds. Research and development of indigenous drugs. New Delhi: Institute of History of Medicine and Medical Research, 1989:78. 91. Mirsky A, Gitelson S, Perisuti G. Effect of tolbutamide on the diabetogenic action of somatotropin. Endocrinology 1959:46:766. 92. Luken FDW, Dohan FC, Wolcott MW. Pituitary diabetes in cat recovery following phlorizin treatment. Endocrinology 1943;32:475. 93. Bhargava KP. Central adrenergic mechanisms for ovulation. Indian J Pharmacol 1970;2:42-56.

76. Gupta SS, Variyar MC. Experimental studies on pituitary diabetes Part.lV. Effect of Gymnema sylvestreand Coccinia indica against the hyperglycaemic response of Somatotropin and Corticotropin hormones. Indian J Med Res 1964; 52:200-7. 77. Gupta SS, Valaderus JRE, Garg VP, Mahesh Rai. Further observation on the diabetic effects of Tinospora cordifolia and casearia esculenta. Indian J Physiol and Pharmacol 1967;56:11. 78. Gupta SS. Effect of G y m n e m a sylvestre and p t e r o c a r p u s marsupium on glucose tolerance in albino rats. Indian J Med Sci 1963:6:501-5. 79. Joglekar GV, Chaudhary NY, Aiman R. Effect of indigenous plant extract on glucose absorption in mice. Indian J Physiol and Pharmacol 1959;3:76.

94. Gupta SS. Drugs and agents used for fertility control - A pharmacological approach. Indian J Physiol and Pharmacol 1972;16:289- 94. 95. Kamboj VP, Kar AB. Development of non-steroidal orally active post coital contraceptives. Indian J Pharmacol 1972;22:26. 96. Kamboj VP. A review of Indian medicinal plants with interceptive activity. Indian J Med Res 1988;57:336-55.

80. Chakravarti BK, Gupta S, Gambhir SS, Gode KD. Pancreatic beta cell regeneration a novel anti-diabetic mechanism of Pterocarpus marsupium. Indian J Pharmacol 1980;12:123-5. 81. Ojha JK, Bajpai HS, Sharma PV. Hypoglycaemic effect of Pterocarpus marsupium roxb (Vijaysar). J Res Indian Med Yoga and Homoeo 1978;13:12-6. 82. Gupta SS. Verma SCL, Garg VP, Khandelwal P. A few observation on the anti-diabetic effect of Tinospora cordifolia and casearia esculenta. Indian J Physiol and Pharmacol 1965;9:9. 83. Gupta SS, Verma SCL, Garg VP, Khandelwal P. Studies on the anti- diabetic effect of Casearia esculenta. Indian J Med Res 1967;55:754-63. Gupta SS, Verma SCL, Garg VP, Rai M. Anti-diabetic effects of Tinospora cordifolia-Part I. Effect on fasting blood sugar level, glucose tolerance and adrenaline induced hyperglycaemia. Indian J Med Res 1967;55:733-45.

97. Kamboj VP, Dhawan BN. Research on plants for fertility regulation. J Ethanopharmacol 1982:6:191-226. 98. Chaudhary RR, Haq M. Review of plants screened for anti-fertility activity. Bull Medico Ethno Bot Res 1980;1 : 420-7. 99. Vohora SB, Khan MSY. Search for anti-fertility drugs from herbal sources. In: Dandiya PC, Vohora SB, eds. Research and development of indigenous drugs. New Delhi: Institute of Hist Med and Med Res, 1989:159. 100. Prakshi A, Chakrabarti B. Anti-estrogenic and anti-implantation effect of aristolic acid from Aristolochica indica (Linn). Indian J Exp Biol 1978;16:1283. 101, Bhargava SK. Estrogenic and pregnancy interceptory effect of flavonoid (Vi-II) of Vitex negundo L.seed in mice. Plant Med Phytotherap 1984;18:74.

84.

85. Gupta SS, Seth CB. Effect of Momordica Chirantia L i n n (Karela) on glucose tolerance in albino rats. J Indian Med Assoc 1962;39:581-4. 86. Kulkarni RD, Gaitonde BB. Potentiation of tolbutamide action by jasad bhasm and Karela (Momordica Charantia). Indian J Med Res 1962;50:715. 87. Baldwa VS, Goyal RK, Bhandari CM, Pangariya. A clinical trial of insulin obtained from vegetable source (Plant insulin) in patient with diabetes mellitus. Rajasthan Med J 1976; l6:54. GuptaSS, Seth CB, Mathur VS. Effect of Gurmarand Shilajit on body weight of young rats. Indian J Physiol and Pharmacol 1965;9:87-92. Gupta SS. Experimental studies on pituitary diabetes PartV. Effect of Shilajir Ficus bengalensis and anterior pituitary

102. Pillai NR, Alam M, Purshothaman KK. Studies on the antifertility activity of oleonolic acid 3c glucoside (RDg-1). J Res Indian Med Yoga and Homoeo 1977;12:26. 103. Garg SK, Mathur VS, Chaudhary RR. Screening of Indian plants for anti-fertility activity. Indian J Exp Biol 1978;16:1077. 104. Kirby DR, Pott DM, Wilson IB. On the orientation of the implanting blatocyst. J Embryol Exp Morph 1967;17:527-32. 105. Gupta SS, Gulati B, Alvi Nishat. Sterility and infertility in relation to histamine release from endometrial tissue. Indian J Physiol and Pharmacol 1969;13:57.

88.

89.

12 S.S. G U P T A

106. Gulati B, Gupta SS, Alvi Nishat, Tiwari KK. Infertility and sterility in relation to histamine content of endometrium. Indian J Med Res 1971;58:1172-5. 107. Batta SK, Santhakumari G. The antifertility effect of Ocimum sanctum and Hibiscus rosa sinensis. Indian J Med Res 1971:59:777.

115. Kuppurajan K, Rajagopalan SS, Sitaraman R, Rajagopalan V, Janki Revathi R, Venkataraghvan S. Effect of Ashwagandha (Withania somnifera) on process of aging in human volunteers. J Res Ayur Siddha 1980;1:247. 116. Singh N, Nath R, Gupta ML. A pharmacological evaluation of antistress activity of Diospyros perigrina (Gurke). Indian J Pharmacol 1988:20: 102-8. 117. Dixit SP, liwari PV, Gupta EM. Experimental studies on the immunological aspects of Atibala (Abutilon indicum Linn), Mahabala (Sida rhombofolia), Bala (Sida cardifolia Linn) and Bhumibala (Sida veronicaefolium). J Res Indian Med Yoga and Homoeo 1978;13:50-6.

108. Chaudhary RR. Plants with possible anti-fertility activity. ICMR special report series 1966;55: 109. Singh MM, Wadhwa V, Kamboj VP. Effect of Centchroman on tubal transport and preimplantation embryonic development in rats. J Reprod Fertil 1986;76:317-24. 110. Brekhman II, Dordymon IV. New substances of plant origin which increase non-specific resistance. Ann Rev Pharmacol 1969:9:419- 30. Bhargava KP, Singh N. Antistress activity in Indian Medicinal plants. J Res Edu Ind Med 1985;4:27. Singh N, Verma P. Mishra N, Nath R. A comparative evaluation of some antistress agents of plant origin. Indian J Pharmacol 1991;21:99. Singh N, Nath R, Lata A, Singh SP, Kohli RT, Bhargava KP. Withania somnifera (Ashwagandha) a rejuvinating herbal drug which enhances survival during stress (an adaptogen). Int J Crude Drug Res 1982;30:29-35. Sharma K, Vali Pasha K, Dandiyan PC. Is Boerhava diffusa Linn (Punernava) an antistress drug?. Indian J Pharmacol 1991;23:45.

111.

118. Dhawan BN. Anticancer and antiviral activity of Indian Medicinal Plants. In: Vasudevan DM, Hay, Maheshwari RK, eds. Proceedings Indo-US workshop on virus and human cancer. Trichur: Amla Research Centre, 1987:67. 119. Acharya SK, Dasarathy S, Tandon A, Joshi YK, Tandon BN. A preliminary open trial of interferon stimulator (SNMC) derived from Glycyrrhiza glabra in the treatment of subacute hepatic failure. Indian J Med Res 1993;98:69-74. 120. Bose BC, Gupta SS, Sultan Mohamad. Studies on enzymes in synthesis of nicotine alkaloids in tobacco plant. Indian Chem Soc 1958;33:81-2.

112.

113.

114.

121. Agrawal KP. Anti-atherogenic blood lipid profile in asthmatics and its modulation by anti-asthma drugs. Indian J Aller Appl lmmunol 1987;1:1-2.