A phytotherapeutic approach to modern drug development can provide many invaluable drugs from traditional medicinal plants. Search for pure phytochemicals as drugs is time consuming and expensive. Numerous plants and polyherbal formulations are used for the treatment of liver diseases. However, in most of the severe cases, the treatments are not satisfactory. Although experimental evaluations were carried out on a good number of these plants and formulations, the studies were mostly incomplete and insufficient. The therapeutic values were tested against a few chemicals-induced subclinical levels of liver damages in rodents. Even common dietary antioxidants can provide such protection from liver damage caused by oxidative mechanisms of toxic chemicals. However, experiments have clearly shown that plants such as Picrorrhiza kurroa, Andrographis paniculata, Eclipta alba, Silibum marianum, Phyllanthus maderaspatensis and Trichopus zeylanicus are sufficiently active against, at least, certain hepatotoxins. Screening plants for antihepatitis activities remains in its infancy. P.kurroa, E. alba, Glycyrrhiza glabra, A. paniculata and P. amarus are likely to be active against Hepatitis B virus. In the case of severe liver damage, most of the liver cells die or turn into fibrotic state. In this case, the treatment should include in addition to the therapeutic agents, agents which can stimulate liver cell proliferation. For developing satisfactory herbal combinations to treat severe liver diseases, plants have to be evaluated systematically for properties such as antiviral activity (Hepatitis B, Hepatitis C, etc), antihepatotoxicity* (antioxidants and others), stimulation of liver regeneration and choleretic activity. The plants with remarkable activities for each of the above properties have to be identified. Single plant may not have all the desired activities. A combination of different herbal extracts/'fractions is likely to provide desired activities to cure severe liver diseases. Development of such medicines with standards of safety and efficacy can revitalise treatment of liver disorders. * hepatoprotective activity.

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Objectives: To study the anti-inflammatory effect of Zingiber officinale, Vitex negundo and Tinospora cordifolia on carrageenin induced hind paw oedema and cotton pellet granuloma in rats. Methods: Hind paw oedema was produced by subplanter injection of carrageenin and paw volume was measured plethysmometrically at '0' and '3' hours intervals after injection. Cotton pellet granuloma was produced by implantation of 50(1mg sterile cotton in each axilla under ether anaesthesia. The animals were treated with Zingiber officinale, Vitex negundo, Tinospora cordifolia and the standard drugs acetylsalicylic acid and phenylbutazone. Results: Zingiber officinale, Vitex negundo and Tinospora cordifolia produced significant anti-inflammatory effect in both acute and subacute models of inflammation. In acute inflammation, effect of Tinospora cordifolia was more than acetylsalicylic acid. In subacute inflammation, the results of these drugs were less than phenylbutazone. Conclusion: Zingiber officinale, Vitex negundo and Tinospora cordifolia possess anti-inflammatory effects in both acute and subacute inflammation.

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Objective: To study the neuropsychobehavioural effects of traditional silver preparations: Raupya Bhasma, Kushta Nuqra and Chandi Warq. Methods: The preparations were subjected to a battery of 30 tests for general neuropsychopharmacological effects, cognitive functions, antidepressant, anxiolytic, neuroleptic and serenic activities, effects on growth, body weight, endurance and fatigue. Results: The test drugs (50 mg/kg, p.o.) caused significant reduction of haloperidol-induced catalepsy in rats. Incorporation in the diet of rat pups (1% w/w for 6 weeks) lead to significantly higher growth rate when compared to control animals. No appreciable effects were discernible on other parameters. Conclusion: Silver preparations used in Ayurveda and Unani-Tibb showed anticataleptic and growth promoting effects without gross or subtle toxicities, weight loss, sedation, motor deficit, aggression or ill effects on cognitive functions.

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Objective: The efficacy of ivermectin pour on formulation (Ivomec pour on) against gastrointestinal nematodiasis in cattle ( Bos indicus), its effect on the blood parameters and the live weight gain of the host was investigated. Methods: The cattle harbouring the gastrointestinal nematodes were treated with ivermectin pour on formulation at the dose rate of 500 (g/kg body weight topically along the back line. The faecal samples and blood parameters were investigated at day 0,7,14, 21 and 28 post treatment, and live body weight gain was evaluated at day 0 and 28 post treatment. Results: Ivermectin pour on formulation was found to be 100% effective against gastrointestinal nematodes in cattle. After 28 days of treatment both haemoglobin and PCV values were significantly increased while ESR was significantly decreased after 14 days of treatment. Body weight of cattle was increased by 6.25% after 28 days of treatment. Conclusion: Gastrointestinal nematodiasis in cattle can be treated successfully with ivermectin pour on formulation. The drug has direct influence on blood parameter and live weight gain of the treated animals. Ivermectin may be useful as an anthelmintic of continued relevance.

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Objectives: To compare the effect of calcium enriched diet (2% CED, 8 weeks), lisinopril (5 mg/kg/day, p.o., 2 weeks) and insulin (1 U/kg/day, s.c., 2 weeks) on blood pressure and vascular reactivity of diabetic rats and diabetic hypertensive rats. Methods: In the first set of experiments, blood pressure and vascular reactivity of diabetic rats (alloxan, 150 mg/kg, i.p., single dose) was compared with that of diabetic rats treated with CED, lisinopril and insulin. In the second set of experiments, blood pressure and vascular reactivity of diabetic hypertensive rats (unilateral nephrectomy followed by DOCA, 25 mg/kg/week, s.c., 5 weeks) was compared with that of diabetic hypertensive rats treated with CED, lisinopril and insulin. Results: Administration of CED and lisinopril significantly reduced the blood pressure and vascular reactivity in diabetic as well as diabetic hypertensive rats whereas insulin reduced these significantly only in the diabetic rats. Conclusion: CED and lisinopril exhibited significant antihypertensive effect in the diabetic hypertensive model.

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The need for a change in the training of undergraduate medical students during the practical sessions in the subject of Pharmacology is felt for a long time. In this article the present situation is reviewed and some introspection is done to consider the appropriate changes. A programme has been structured in view of some important key points like concept, application, rationale & essential drugs. Back ground information about therapeutics and drug-formulations is provided in the form of Handy-Informative-Script. The programme is named as Handy-Informative-Script aided CARE based Programme. It is conducted under four heads: (i) Clinical pharmacy & therapeutics: During these sessions patient-based-therapeutic problems are posed. The students are expected to work on the given exercises with the help of the Handy-Informative Script and to actively participate in discussions meant to defend their therapeutic strategies. (ii) Critical study of a given prescription: Students learn to critically analyse the given prescription. (iii) Pharmaco metrics: In these sessions the students are exposed to experimental pharmacology with a view to improve the understanding of the actions of drugs. (iv) Clinical case presentation by the individual student: In these sessions the students are exposed to the factual realities of drug-use in patients. Feasibility of the training and evaluation based on the entire training programme has been established.

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Objectives: To evaluate the oestrogenic effect of U-3107, a herbal uterine tonic using in vivo and in vitro experimental models. Methods: Oestrogenic effect of U-3107 (1 gm/kg p.o.) was studied in normal and ovariectomized rats. U-3107 was administered as an aqueous suspension for a period of 21 days. The parameters studied in both in vivo models included uterine weight (wet and dry weight), oestrogen and progesterone levels. The effect of U-3107 (1 gm/kg p.o. x 21 days) was also studied in normal rats on regular oestrus cycle. In vitro studies with U-3107 (50-400 (g/ml of aqueous extract) on isolated uterus in non-gravid, nonoestronised rats were carried out to find out whether the formulation possesses any oxytocin like activity. Results: Administration of U-3107 in normal rats significantly increased the wet and dry uterine weight. It also resulted in marked increase of oestrogen levels with no change in progesterone levels as compared to control. U-3107 treatment in ovariectomized rats did not show any increase in uterine weight. The rats from both control and treated group showed normal oestrus cycle. Aqueous extract of U-3107 failed to produce contractile response on the uterus when exposed in vitro and decreased spasmogen-induced contraction. Conclusion: U-3107 possess oestrogenic activity only in the presence of functional ovary and is devoid of any progestational activity.

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Objective: To study the effect and mechanism of action of Isomeric Juglones on the isolated frog heart. Method: The response of dosage forms of four Isomeric Juglones namely juglone, plumbagin, lawsone and phthiocol were investigated on isolated frog heart preparation. Their interaction with calcium channel blockers namely verapamil, nifedipine and diltiazem was studied to elucidate the mechanism of action. Result: Administration of juglone (10-100 mcg), lawsone (10 mcg -1 mg) plumbagin (1-100 mcg) and phthiocol (1-80 mcg) showed dose dependent increase in the rate of contraction and force of contraction of heart. The positive inotropic action of juglone (40 mcg), lawsone (80 mcg), plumbagin (8 mcg) and phthiocol (80 mcg) was blocked by verapamil (1 mcg), nifedipine (5 mcg) and diltiazem (10 mcg). Conclusion: The Isomeric Juglones showed positive inotropic and chronotropic action on the frog heart. The mechanism of action of these Isomeric Juglones indicated involvement of calcium channels.

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Objectives: To study the effect of pentazocine on some selected skeletal muscle preparations and the antagonism of its effect by some neuromuscular blocking agents. Methods: In isolated rectus abdominis muscle preparation of the toad ( Buffo regularis) the response of acetylcholine and pentazocine were obtained in the absence and in the presence of d-tubocurarine and the potency ratio was calculated. The effect of pentazocine on the hemidiaphragm response to electrical stimulation of phrenic nerve was studied in Bulbring's isolated phrenric nerve diaphragm preparation. The antinicotinic activity of pentazocine was also studied in the day-old chick. Results: Pentazocine potentiates acetylcholine-induced contraction of the toad rectus muscle and per.sc induces contraction of the toad rectus muscle which was antagonised by tubocurarine in a noncompetitive manner giving a potency ratio of acetylcholine: pentazocine of 1:2; impairs indirectly evoked contractions of the rat diaphragm where tubocurarine was at least 3 times more potent than pentazocine produces ataxia in day old chicks and antagonises tubocurarine and suxamethonium induced paralysis in vivo. Conclusion: Pentazocine, like other opioids, acts directly on the skeletal muscle to impair its functions and exerts antagonism against selected neuromuscular blocking agents.

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Objectives: To examine the effect of aluminium (Al) on different types of phosphatases in rat brain in the presence and absence of Ca 2+ channel blockers. Methods: Phosphoprotein phosphatase activities were measured in brains of male Sprague Dawley rats treated with aluminium chloride (AlCl3 ) , Ca2+ channel blockers per se and AlCl3 with Ca2+ channel blockers for 40 days using standard techniques. Results: Tyrosine phosphoprotein phosphatase (TPP) activity, activation of TPP by EDTA and activity of serine/threonine phosphoprotein phosphatase 2B (PP2B) were decreased by Al. Nifedipine treated rats regained the activities of TPP and PP2B and showed increased activity of serine/threonine phosphatase 2C (PP2C). Verapamil and diltiazem were ineffective in restoring the normal activities of the enzymes. Conclusion: The restoration of the activity of PP2B by nifedipine indicates that there may be a competition between Al and Ca and between Al and Ca2+ channel blocker nifedipine. Hence the Ca 2+ channel blocker nifedipine can be used to prevent Al 3+ toxicity.

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Objective: To study the effect of gentamicin on humoral and cell mediated immune system in rabbits. Methods: Rabbits were treated with gentamicin at 4 mg/kg and 8mg/kg body weight doses for 5 days along with single intramuscular injection of 0.5 ml of Brucella plain killed antigen and humoral and cellular immune responses were measured. Results: There was no significant variation in the humoral and cellular immune response between the antigen control and the groups given gentamicin along with antigen. Conclusion: Gentamicin at the two dose levels used for 5 days, in rabbits, did not affect the specific immune response.

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Objective: To study the effects of chronic administration of imipramine on the hyperactivity of hypothalamic-pituitary- adrenal (HPA) axis in neonatal clomipramine model of depression. Methods: Male rat pups were given clomipramine (15 mg/kg, s.c., twice daily) or equivolume of saline from the time they were five days old and until they were twenty-one days old. At three months of age, clomipramine treated rats were administered either imipramine (20 mg/kg, s.c.,) or saline once daily for 14 days. Serum corticosterone level was estimated before and after dexamethasone (100( g/kg, s.c.,) administration in all animals. Results: Data indicated an enhanced baseline corticosterone level and nonsuppression to dexamethasone in clomipramine treated rats. The levels of corticosterone was reduced to the levels of control group in rats subjected to 14 days of imipramine treatment. Conclusion: Neonatal treatment of clomipramine produced dysregulation of HPA axis, and this neuroendocrine abnormality was reversed with chronic administration of imipramine.

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Objective: To study the neuropsychobehavioural effects of traditional silver preparations: Raupya Bhasma, Kushta Nuqra and Chandi Warq. Methods: The preparations were subjected to a battery of 30 tests for general neuropsychopharmacological effects, cognitive functions, antidepressant, anxiolytic, neuroleptic and serenic activities, effects on growth, body weight, endurance and fatigue. Results: The test drugs (50 mg/kg, p.o.) caused significant reduction of haloperidol-induced catalepsy in rats. Incorporation in the diet of rat pups (1% w/w for 6 weeks) lead to significantly higher growth rate when compared to control animals. No appreciable effects were discernible on other parameters. Conclusion: Silver preparations used in Ayurveda and Unani-Tibb showed anticataleptic and growth promoting effects without gross or subtle toxicities, weight loss, sedation, motor deficit, aggression or ill effects on cognitive functions.

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Objective: To investigate the role of mtNOS in cerebral ischaemia in Mongolian gerbils. Methods: Mitochondria isolated after 5 min of ischaemia and after 48 and 72 hrs of restitution of blood flow was used. Animals were pretreated with fast Na + channel blocks (TTX) and NOS inhibitors (L-NAME, 7-NI). Following estimations were made: (i) respiratory main complexes (ii) NAD(P)H/NAD(P) levels (iii) mitochondrial membrane potential and (iv) DNA pattern. Results: LDH estimated in the venous outflow was elevated. Respiratory main complexes I, II and III except IV were altered in ischaemic group. NAD(P)H/NAD(P) levels were elevated, significant decrease with TTX in all groups was observed. Ischaemia dissipated mitochondrial membrane potential. This was reverted close to normal values by TTX, 7-NI and L-NAME in the order of their efficacy. No significant change in DNA pattern was observed. Conclusion: Ischaemia induced pathological changes at the mitochondria level are presented by TTX and L-NAME. They may find possible use for therapeutic interventions in neurodegenerative disorders.

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