Ethanolic extract of Azadirachta indica ameliorates ovarian defects through phosphoinositide-3 kinase inhibition in a rat model of polycystic ovary syndrome

Objective:To assess the therapeutic potential of ethanolic extract of Azadirachta(A.)indica in rats with polycystic ovary syndrome(PCOS).Methods:Thirty-five prepubertal female Sprague Dawley rats were randomly divided into five groups with 7 animals in each group.Group 1 received 0.5%carboxy methyl cellulose orally.Groups 2 to 5 received testosterone propionate(0.2 mg/kg,s.c.)dissolved in olive oil daily for 42 days to induce PCOS.In addition,group 3 was administered with A.indica extract(100 mg/kg,0.5%carboxy methyl cellulose orally)from the 7th to 12th week,group 4 received quercetin(100 mg/kg,0.5%carboxy methyl cellulose orally)and group 5 received wartmannin(100 mg/kg,0.5%carboxy methyl cellulose orally).At the end of treatment,blood was collected for biochemical evaluation.Total follicular count and uterus corpus luteum count followed by PI3K gene expression in the ovary and uterus were evaluated.Results:The ethanolic extracts of A.indica significantly reduced body weight,ovary weight and uterus weight of rats.Extracts of A.indica also significantly increased the levels of serum glucose,total cholesterol,triglyceride,low-density lipoprotein,very low-density lipoprotein,insulin,testosterone,and luteinizing hormone.Treatment also reduced lipid peroxidation and increased antioxidant parameters in the liver homogenates of PCOS-induced rats.Histological examination of the ovary and uterus confirmed PCOS occurrence and remission state in the PCOS-induced and treated groups,respectively.Moreover,A.indica and quercetin significantly downregulated PI3K gene expression.Histopathological results of the ovary and uterus also proved the protective role of A.indica.Conclusions:A.indica leaf extract has beneficial effects in the treatment of PCOS by downregulation of PI3K gene expression.