Trupti C. Deshpande* and Hemant D. Une Pages 1 - 12 ( 12 )
Background: Oxidative stress is caused due to the overproduction of the reactive oxygen species (ROS) and the disturbance developed in the antioxidant potential of biochemical processes. ROS mostly formed in the brain due to the high consumption of oxygen and the insufficiency of endogenous antioxidant resistance mechanisms. Cytochrome P450 2E1 has an excessive percentage of NADPH oxidase activity, which causes the production of ROS and increases oxidative stress.
Objectives: We have studied the effect of Ethyl Acetate Extract of Achyrantes Aspera (EAAA) on ROS in the brain of diabetes-induced rats. We have also investigated the possible molecular mechanism of reduction in ROS through molecular docking. Methods: To study the oxidative stress induced by ROS in diabetic rats, we have estimated the ROS in rat brain through Flow cytometry. The oral dose of EAAA 50mg/kg and 100 mg/kg were given to diabetes induces rats. Results were articulated as mean ± standard deviation (SD). Data were analyzed using analysis of variance (ANOVA) followed by Bonferroni as a post hoc test. We have performed molecular docking of flavonoids on CYP2E1 to study the inhibitory potential.
Results: The results have shown that EAAA reduces the generation of ROS in the diabetes-induced rat in a dose-dependent manner. The oral dose of EAAA 50mg/kg and 100 mg/kg was given to the rat and the ROS generation got affected accordingly. Luteolin, Quercetin, and Apigenin have inhibited the CYP2E1 very effectively. Luteolin has formed 4 hydrogen bonds with CYP2E1 which indicate its potential inhibition. Although, Luteolin and Apigenin have shown a very good binding affinity with the enzyme.
Conclusion: From the present work we have concluded that the Ethyl Acetate Extract of Achyrantesaspera can effectively inhibit the ROS generation in the diabetes-induced rats by inhibiting the activity of CYP2E1.
Reactive Oxygen Species (ROS); Achyrantes Aspera; CYP2E1; Flow cytometry; Diabetes; Rats
Department of Pharmacology, JSPM’s Rajarshi Shahu College of Pharmacy & Research, Pune, Maharashtra,, Department of Pharmacology, Y.B. Chavan College of Pharmacy, Aurangabad, Maharashtra