Effect of alpha-mangostin on olanzapine-induced metabolic disorders in rats

Objective(s): As olanzapine has side effects such as weight gain and metabolic disorders, and alpha-mangostin has been shown to control metabolic disorders, the effects of alpha-mangostin on metabolic disorders induced by olanzapine were investigated in this study.Materials and Methods: Obesity was induced in female Wistar rats by daily administration of olanzapine (5 mg/kg/day, IP, 14 days). Rats were divided into 6 groups:1) vehicle (control); 2) olanzapine (5 mg/kg/day); 3,4,5) olanzapine+ alpha-mangostin (10, 20, 40 mg/kg/day, IP); 6) alpha-mangostin (40 mg/kg/day). Weight changes were measured every 3 days and food intake was assessed every day. Systolic blood pressure, plasma levels of blood sugar, triglycerides, total cholesterol, HDL, LDL, leptin, oxidative stress markers (MDA, GSH), AMPK, and P-AMPK protein levels in liver tissue were assessed on the last day of the study. Results: Administration of olanzapine significantly increased weight gain, food intake, blood pressure, triglycerides, LDL, blood sugar, leptin, and MDA in rat liver tissue and also decreased GSH, AMPK, and P-AMPK in liver tissue compared with the control group. Different doses of alpha-mangostin significantly reduced weight gain, food intake, systolic blood pressure, triglycerides, LDL, blood sugar, leptin, and MDA. Also, they significantly increased GSH, AMPK, and P-AMPK in liver tissue compared with the olanzapine group.Conclusion: Olanzapine increases leptin levels, food intake, and weight, induces oxidative stress, decreases the levels of AMPK and P-AMPK proteins in liver tissue, and causes metabolic disorders. But, alpha-mangostin reduces the negative effects of olanzapine by activation of AMPK.