Department of Management
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Item Effects of adhatoda vasica leaf extract in depression co‑morbid with alloxan‑induced diabetes in mice(IJGP, 2014) Mahesh, R.Context: Increased neuronal oxidative stress as a consequence of diabetes may result in neuropsychological complications such as depression. Depression co‑morbid with diabetes further hampers the quality life years in diabetic patients. Aim: Thus, the present study was aimed at investigating the effects of Adhatoda vasica leaf extract (EAV), as a natural remedy, in alloxan‑induced diabetes and co‑morbid depression in mice. Materials and Methods: Experimentally, mice were rendered diabetic with a single dose of alloxan of 200 mg/kg, intraperitoneally (i.p.). After 3 weeks of having chronic diabetic state, mice were given EAV (100-400 mg/kg, orally)/ vehicle/standard control (escitalopram, ESC; 10 mg/kg, orally) for 7 days. After dosing, anti‑diabetic effect was detected by the fasted blood glucose levels and anti‑depressant effect was evaluated by behavioural despair tests, followed by monoamine oxidase (MAO) activity and oxidative stress analysis. Results and Discussion: EAV treatment effectively reduced the elevated blood glucose levels and reversed co‑morbid depressive behaviour. Furthermore, EAV inhibited diabetes induced increased oxidative stress and MAO activity in the brain. Thus, EAV demonstrated the potential protective action against oxidative stress and revealed monoamine modulatory activity in the brain, which may contribute to its anti‑depressant effect. Conclusion: This work demonstrates the efficacious effect of EAV in reversing the depression co‑morbid with alloxan‑induced diabetes in mice.Item Protective effects of a novel 5-HT3 receptor antagonist, N-n-butyl-3-methoxy quinoxaline-2-carboxamide (6o) against chronic unpredictable mild stress-induced behavioral changes and biochemical alterations(Elsevier, 2014-07) Mahesh, R.Stimulation of high oxidative stress in the brain is considered as an important factor for neurotoxicity towards the pathophysiology of chronic stress-induced depression disorder. In the present research, a potential 5-HT3 receptor antagonist N-n-butyl-3-methoxy quinoxaline-2-carboxamide (6o) having good Log P (2.60) and pA2 (7.7) values was examined for its effect on the behavioral and biochemical changes induced by the chronic unpredictable mild stress (CUMS) model. In the current investigation mice were introduced to different stress procedures daily for a period of 28 days to induce a depressive-like behavior. The results show that CUMS caused a depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and locomotor activity and increase in immobility in the forced swim test (FST). Moreover, it was found that oxidative stress markers such as lipid peroxide and nitrite levels were significantly increased, whereas, antioxidant enzymes such as glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) levels were decreased in the brain tissue of CUMS-subjected mice. “Compound 6o” (1 and 2 mg/kg, p.o.) and fluoxetine treatment (20 mg/kg, p.o.) for a period of 21 days altered the CUMS-induced behavioral (increased immobility period, reduced sucrose preference and decreased locomotor activity) and biochemical (increased lipid peroxide, increased brain nitrite; decreased GSH, SOD and CAT levels) alterations. Moreover normal mice treated with “compound 6o” (2 mg/kg, p.o.) showed a significant decrease in the duration of immobility in FST as compared to normal vehicle treated mice. In conclusion, “compound 6o” produced antidepressant-like effects in behavioral despair paradigm in chronically stressed mice by restoring antioxidant enzyme activityItem Effect of (4a) a novel 5-HT3 receptor antagonist on chronic unpredictable mild stress induced depressive-like behavior in mice: an approach using behavioral tests battery(De Gruyter, 2014) Mahesh, R.The inconsistent therapeutic outcome necessitates designing and identifying novel therapeutic interventions for depression. Hence, the present study deals with the investigation of antidepressant-like effects of a novel 5-HT3 receptor antagonist (4-phenylpiperazin-1-yl) (quinoxalin-2-yl) methanone (4a) on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alterations.