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

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. 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.  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. 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.