Lupeol attenuated the NAFLD and PCOS-induced metabolic, oxidative, hormonal, histopathological, and molecular injuries in mice

BACKGROUND AND PURPOSE: The current study aimed to study the therapeutic effects of lupeol as a nutritional triterpene on non-alcoholic fatty liver disease (NAFLD) and polycystic ovarian syndrome (PCOS) disorders in separate and concurrent models. EXPERIMENTAL APPROACH: This study was performed in three sets and each set contained 4 groups of female mice (n = 6), including control, NAFLD or PCOS and/or NAFLD/PCOS, lupeol, and metformin (MET). The treatment groups following the induction of disorders were treated with lupeol (40 mg/kg, orally) or MET (500 mg/kg, orally) for 28 days. The insulin resistance index and hormonal assessments were conducted on the collected serum samples. Moreover, oxidative stress biomarkers were measured in the liver and ovaries. Histopathological studies and ultimately any changes in the expression of androgen receptors, toll-like receptor (TLR)-2 and TLR-4 were analyzed. FINDINGS/RESULTS: Results revealed that lupeol reduced significantly the insulin resistance index in NAFLD and NAFLD/PCOS-positive animals. Lupeol attenuated remarkably the PCOS and PCOS/NAFLD-elevated concentration of testosterone. lupeol recovered the metabolic disorders-induced oxidative stress and restored the disorders-depleted glutathione. The NAFLD/PCOS-induced hepatic damages such as microvesicular or macrovesicular steatosis and atretic follicles number in the ovary were attenuated in the lupeol-treated mice. Serum level of TNF-α was reduced and the expression of androgen receptors, TLR-4 and TLR-2 were downregulated in the lupeol-treated NAFLD/PCOS-positive animals. CONCLUSIONS AND IMPLICATION: The results suggest that lupeol could be a novel nutraceutical for the treatment of metabolic disorders. Lupeol's anti-metabolic disorders effects attribute to its anti-dyslipidemia, antioxidant, and anti-inflammatory properties.