ANTIDEPRESSANT LIKE EFFECT OF NEWLY SYNTHESIZED COMPOUND 2[(N- BENZYLACETAMIDO) MERCAPTO] BENZIMIDAZOLE (VS 25) AND ITS POSSIBLE MECHANISM BY INHIBITION OF MONOAMINE OXIDASE ENZYME IN MICE

Objective: The objective of the study was to investigate the antidepressant activity of a newly synthesized compound 2 [(N-benzylacetamido) mercapto] benzimidazole (VS 25) by forced swimming test in mouse and to explore the mechanism of action by its effect on monoamine oxidase enzyme in mouse brain.Methods: Swiss albino mice were randomly divided into 4 groups, each containing 6 animals. Group one was controlled and received 1 % cmc, p. o., Group II received moclobemide (50 mg/kg) p. o., group three and four received VS25 (30mg/kg and 60 mg/kg) once a day for 14 days.Results: In the forced swim test the decrease in immobility was 38.10% in moclobemide treated mice compared to 34.66% in VS25 (30 mg/kg) and 28.77% in VS 25 (60 mg/kg) treated mice. The percentage inhibition of the monoamine oxidase enzyme in mouse brain mitochondria was in moclobemide treated animals was 75.19% compared to 66.94% in VS 25 (30mg/kg) and 55.52% in VS 25 (60 mg/kg) treated animals. Moclobemide did not inhibit MAO B enzyme while VS25 (30 mg/kg) showed 6.48% and VS 25 (60 mg/kg) showed 4.75% inhibition.Conclusion: It is concluded that both moclobemide (50 mg/kg) and VS25 (30 mg/kg) showed antidepressant activity in mice. Moclobemide selectively inhibited MAO A enzyme in mouse brain. VS 25 (30 mg/kg) was equipotent as MAO A inhibitor but differed from moclobemide with respect to weak inhibition of MAO B activity also.Â

Effect of Cyclodextrin Garcinol Complex on Pressure Overload- Induced Cardiotoxicity and Cardiac Hypertrophy by Aortic Stenosis in Rats

Background: Garcinol is a polyisoprenylated benzophenone derived from rinds of fruit of Garcinia species namely Garciniaindica (common name ‘Kokum’) and Garcinia cambogia (common name ‘Gombogee’). Garcinol is not stable and has poor bioavailability which can be improved by complexing garcinol with cyclodextrin (cyclodextringarcinol complex). Objective: The objective of the present study was to investigate effect of cyclodextrin-garcinol complex (20 mg/kg/) on pressure overloadinduced cardiotoxicity and cardiac hypertrophy by aortic stenosis in rats. Methods: Male Wistar rats (250-300g) were divided into following four groups such as: control, sham, stenosis and cyclodextrin-garcinol complex. Daily body weights were recorded. Cyclodextrin-garcinol complex (20 mg/kg/day) in distilled water, was administered orally to rats daily for 18 days and then the animals underwent surgery with aortic binding, the treatment was continued up to 4-6 weeks. Haemodynamic changes and electrocardiogram (ECG) were recorded in anaesthetized rats. Results: Pressure overload induced by arotic stenosis in rat resulted in significant myocardial hypertrophy and decreased endogenous antioxidants when compared with the control and sham group animals. Cyclodextrin-garcinol complex (20 mg/kg) showed significant cardioprotective activity by lowering the myocardial hypertrophy, level of lipid peroxidation (MDA content) as well as elevated the level of GSH. The results suggest pre-treatment of cyclodextrin-garcinol complex (20 mg/kg), may offer potential benefits in the management of cardiotoxicity and cardiac hypertrophy. Conclusion: It is concluded that cyclodextrin-garcinol complex (20 mg/kg) protected the haemodynamics of stenosized heart of rats by reduction of lipid peroxidation and preservation of endogenous antioxidants in rat heart

Effect of cyclodextrin garcinol complex on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats

Background: Garcinol is a polyisoprenylated benzophenone derivative present in the fruit rinds of Garcinia species namely Garcinia indica (common name 'Kokum') and Garcinia cambogia (common name 'Gombogee'). It appears to be involved in the regulation of oxidative stress and antioxidant capacity of heart tissue when the heart is subjected to oxidative stress in various pathogenic conditions/ chemical agent. But garcinol is associated with severe limitation of instability and poor bioavailability which can be improved complexing cyclodextrin with garcinol (garcinol complex). Objective: The objective of the present study was to investigate effect of cyclodextrin with garcinol complex (20 mg/kg), on Iso induced cardiotoxicity and cardiac hypertrophy in rats.Methods: Male Wistar rats (250-300g) were divided into following 4 groups of six animals each. Group 1 was control (distilled water 2 ml/kg/day orally for 18 days and water for injection by i.p. from day 9 to day 18), group 2 was cyclodextrin (cyclodextrin 2 ml/kg/day orally for 18 days and water for injection by i.p. from day 9 to day 18), group 3 Iso (distilled water 2 ml/kg/day orally for 18 days and isoproterenol 1 mg/kg by i.p. from day 9 to day 18), group 4 garcinol complex (20 mg/kg/day orally for 18 days and isoproterenol 1 mg/kg by i.p. from day 9 to day 18). After 24 hrs of last dose of isoproterenol, electrocardiogram (ECG) and heart rate were recorded in anaesthetized rats. The animals were sacrificed by overdose of ether. The hearts of animals were isolated for measurement of reduced glutathione (GSH) and lipid peroxidation (MDA). Results: Isoproterenol treated rats showed significant myocardial hypertrophy, decreased endogenous antioxidants when compared with the control group animals. The garcinol complex (20 mg/kg) treatment for 18 days showed significant cardioprotective activity by lowering the myocardial hypertrophy, level of lipid peroxidation (MDA content) as well as elevated the level of GSH. The results suggest pre-treatment of garcinol complex (20 mg/kg), may offer potential benefits in the management of cardiotoxicity and cardiac hypertrophy. Conclusion: It is thus concluded that Garcinol Complex (20 mg/kg) administration offered significant protection against isoproterenol induced cardiotoxicity and cardiac hypertrophy as well as decreased myocardial injury by preservation of endogenous antioxidants and reduction of lipid peroxidation in rat heart

Neuroprotective effect of Azadirachta indica standardized extract in partial sciatic nerve injury in rats

Chronic neuropathic pain is a common and widely recognized pain syndrome for patients and difficult to manage for physicians. Azadirachta indica (AI) possesses analgesic, anti-inflammatory, and antioxidant properties. To evaluate the neuroprotective effect of AI standardized extract in an animal model of peripheral neuropathy induced by partial sciatic nerve ligation (PSNL). PSNL was induced in male Wistar rats (180-200 g) with tight ligation of the nerve. Rats received treatment with either vehicle i.e. distilled water (PSNL control), Pyridoxine (100 mg/kg, p.o.) or AI (100, 200 and 400 mg/kg, p.o.) for 28 days. Various behavioral parameters, biochemical, molecular and histological parameters were evaluated. PSNL resulted in a significant decrease (p < 0.05) in allodynia, hy- peralgesia, motor coordination and motor nerve conduction velocity (MNCV) whereas chronic treatment with AI (200 and 400 mg/kg) significantly attenuated (p < 0.05) these behavioral changes. Enhanced activity of oxidative- nitrosative stress, inflammatory mediators (TNF-α, IL-1β, and NF-κB) as well as mRNA expression of Bax, Caspase-3, and iNOs were significantly attenuated (p < 0.05) by AI treatment. It also significantly increased (p < 0.05) peripheral blood oxygen content and Bcl-2 mRNA expression. The flow cytometric analysis revealed that AI (200 and 400 mg/kg) treatment significantly attenuated neural apoptosis and reactive oxygen species levels. PSNL induced histological aberrations were also decreased by AI treatment. Azadirachta indica exerts its neuro- protection against PSNL induced neuropathic pain via inhibition of oxidative-nitrosative stress, the release of pro-inflammatory cytokines and apoptosis to improve MNCV (graphical abstract, Figure 1)

Review on the induction of obesity in laboratory animals

AbstractValid animal models are initial essential for successful screening of novel therapeutic strategies against all types of diseases. Development or selection of an animal model that resembles the human disease process and symptoms is dependent on a robust knowledge of the natural history and pathogenesis of the disease. The use of animal models thus becomes to understand the underlying physiological and genetic basis of energy regulation, taste and smell perception and food choice behaviour. Obesity is chronic metabolic disorder results from multiple etiologies like genetic, physiological, epigenetic and environmental factors. Animal models of obesity include direct measurement of food intake to long-term studies in animals exhibiting continuous overconsumption of food containing high calories and fat. It is of prime importance that we must choose the right models with high face, construct and predictive validity. Failing to select and use appropriate animal models impede successful discovery and development of safer and more potent therapeutics and wastage of money and time. We have thus provided a short review on currently available animal models of obesity. We discuss different method of induction of obesity in laboratory animals as well as the transgenic animals used in antiobesity drug discovery.Â

Effect of pretreatment with coenzyme Q10 on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats

AbstractBackground: Coenzyme Q10 (CoQ10) is a lipid-soluble, vitamin-like substance found in the hydrophobic interior of the phospholipid bilayer of most cellular membranes. It appears to be involved in the coordinated regulation between oxidative stress and antioxidant capacity of heart tissue when the heart is subjected to oxidative stress in various pathogenic conditions.Objective: The objective of the present study was to investigate the effect of pretreatment with CoQ10 (100 mg/kg) on isoproterenol (ISO)-induced cardiotoxicity and cardiac hypertrophy in rats.Methods: Albino male Wistar rats (250–300 g) were evenly divided by lottery method into 1 of the following 3 groups: the ISO group (olive oil 2 mL/kg orally for 18 days and ISO 1 mg/kg IP from days 9–18); the CoQ10 + ISO group (CoQ10 100 mg/kg orally for 18 days and ISO 1 mg/kg IP from days 9–18); and the control group (olive oil 2 mL/kg orally for 18 days and water IP from days 9–18). Twenty-four hours after the last dose of water or ISO, the rats were anesthetized and an ECG was recorded. Blood was withdrawn by retro-orbital puncture for estimation of serum creatine kinase-MB (CK-MB) isoenzyme levels, lactate dehydrogenase (LDH) levels, and aspartate aminotransferase activities. The animals were euthanized using an overdose of ether. The hearts of 6 animals from each group were used for estimation of superoxide dismutase (SOD) activity, reduced glutathione (GSH) concentration, lipid peroxidation (LPO), malondialdehyde (MDA), and total protein concentration. Histopathology of the 2 remaining hearts in each group was carried out by a blinded technician.Results: A total of 24 rats (8 in each group) were used in this study; all rats survived to study end. Compared with the control group, the ISO-treated rats had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly higher myocardial MDA concentration [P < 0.001]; significantly lower myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.01]); and significantly higher serum activities of marker enzymes (eg, CK-MB [P < 0.001] and LDH [P < 0.001]). Compared with the ISO group, the CoQ10 + ISO group had a significant change in heart to body weight ratio (P < 0.001); significant changes in the endogenous antioxidants (ie, significantly lower MDA concentration [P < 0.05]; significantly higher myocardial GSH concentration [P < 0.001] and SOD activity [P < 0.05]); and significantly lower serum activities of marker enzymes (eg, CK-MB [P < 0.05] and LDH [P < 0.01]).Conclusion: Pretreatment with CoQ10 (100 mg/kg) for 18 days was associated with moderate protection against ISO-induced cardiotoxicity and cardiac hypertrophy, and with lower myocardial injury by preserving endogenous antioxidants and reducing LPO in rat heart

Interaction of Aqueous Extract of Pleurotus pulmonarius (Fr.) Quel-Champ. with Glyburide in Alloxan Induced Diabetic Mice

Mushrooms are low calorie food with very little fat and are highly suitable for obese persons. With no starch and very low sugars, they are the ‘delight of the diabetics’. Combination of herbal drugs (or isolated phytochemicals) is found to be beneficial in certain diseases when given along with conventional drugs. The aim of the present study was to evaluate the effects of aqueous extract of Pleurotus pulmonarius (Lentinaceae) (called as PP-aqu) and its interaction with glyburide in alloxan induced diabetic mice. The diabetic mice treated were with PP-aqu (500 mg/kg, p.o.) alone or combination with glyburide (10 mg/kg, p.o.) for 28 days. Blood samples were collected by orbital sinus puncture using heparinized capillary glass tubes and were analyzed for serum glucose on 0, 7th, 14th, 21st and 28th days. Body weights and mortality were noted during the study period. In oral glucose tolerance test (OGTT), glucose (2.5 g/kg, p.o.) was administered with either vehicle, PP-aqu alone or in combination with glyburide and serum glucose level analyzed at 0, 30, 60 and 120 min after drug administration. Administration of PP-aqu (500 mg/kg) and its combination with glyburide (10 mg/kg) significantly (P < 0.001) decreased serum glucose level in diabetic mice. In OGTT, glyburide or PP-aqu treatment alone or their combination produced significant (P < 0.001) increase in glucose threshold. Thus we suggest that P. pulmonarius showed potent and synergistic antihyperglycemic effect in combination with glyburide

Antiulcer activity of aqueous extract of leaves of Madhuca indica J. F. Gmel against naproxen induced gastric mucosal injury in rats

Objective: To evaluate antiulcer potential of aqueous extract of Madhuca indica (M. indica) J. F. Gmel leaves in rats. Methods: Aqueous extract of M. indica J.F. Gmel leaves was tested at the dose of 100, 200 and 400 mg/kg, p.o. against naproxen (30 mg/kg, p.o) induced gastric ulcer. Omeprazole (30 mg kg, p.o.) was used as a positive standard. Ulcerated area was measured by Image J software. Various antioxidant parameter like SOD, GSH, MDA, MPO, NO and histamine were also determined. Results: After 4 week treatment period, desired aim was achieved using aqueous extract of plant of M. indica at the dose of 200 and 400 mg/kg, p.o. (P<0.01, P<0.001) showed significant reduction in ulcerated area and ulcer index as compared to control group. Omeprazole (30 mg/kg, p.o.) was more effective in reducing ulcerated area after 30 days treatment period. In addition, SOD, GSH, NO significantly increased; MDA, MPO content significantly lowered when compared with control group. Histamine content didn't show any significant change at all the three doses. Conclusions: Our finding suggests that aqueous extract of M. indica J.F. Gmel leaves is effective in gastric ulcer protection