Loureirin B Reduces Insulin Resistance and Chronic Inflammation in a Rat Model of Polycystic Ovary Syndrome by Upregulating GPR120 and Activating the LKB1/AMPK Signaling Pathway.

Abstract

Polycystic ovary yndrome (PCOS) is a common metabolic disorder in women, which is usually associated with insulin resistance (IR) and chronic inflammation. Loureirin B (LrB) can effectively improve insulin resistance and alleviate chronic inflammation, and in order to investigate the therapeutic effect of LrB on polycystic ovary syndrome with insulin resistance (PCOS-IR), we conducted animal experiments. A PCOS-IR rat model was established by feeding a high-fat diet combined with letrozole (1 mg/kg·d for 21 days). The rats were treated with the GPR120 agonists TUG-891 and LrB for 4 weeks. Biochemical parameters (fasting blood glucose, total cholesterol, triglycerides, high- and low-density lipoprotein), hormone levels (serum insulin, E2, T, LH, and FSH), and inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-18) were analyzed. Histopathological analyses of ovaries were performed using hematoxylin/eosin (H&E) staining. Real-time PCR and western blotting were used to assess GPR120, NLRP3, and caspase-1 expression in ovaries, and immunohistochemistry was used to evaluate LKB1 and AMPK protein expression. LrB reduced body weight, Lee's index, ovarian index, ovarian area, and volume in PCOS-IR rats. It lowered fasting blood glucose, serum insulin, and HOMA-IR. LrB decreased total serum cholesterol, triglyceride, and LDL levels and increased HDL levels. It reduced serum T, LH, and LH/FSH and raised serum E2 and FSH levels. LrB downregulated the mRNA and protein expression levels of NLRP3 and Caspase-1, increased the protein and mRNA expression levels of GPR120 in rat ovaries, and increased LKB1 and AMPK protein expression in ovaries, ameliorating ovarian histopathological changes in PCOS-IR rats. Taken together, LrB upregulated GPR120, LKB1, and AMPK protein expression, downregulated NLRP3 and Caspase-1 protein expression, reduced insulin resistance and chronic inflammation, and ameliorated histopathological changes in ovarian tissues in PCOS rats, suggesting its potential as a treatment for PCOS.