The molecular mechanism of soy isoflavone-oat β-glucan in alleviating polycystic ovary syndrome: Involvement of the TLR4-PI3K/AKT-NF-κB pathway and the regulatory role of miRNA.

Chronic inflammation plays a critical role in the pathogenesis of polycystic ovary syndrome (PCOS). Polysaccharides and polyphenols can form complexes through various interaction mechanisms. This enhances their functional and nutritional properties. This study investigated the molecular mechanisms underlying the effects of the complex (SO), focusing on the TLR4/NF-κB signaling pathway and microRNA regulation. Following treatment with medium (200 mg/kg) or high (300 mg/kg) doses of SO, rats with induced PCOS showed significantly reduced ovarian levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines (IL-6, IL-1β, IL-18, and TNF-α) (P < 0.05). The high-dose group also showed notably enhanced antioxidant activity (P < 0.05), suppressed the upregulation of TLR4, PI3K, and p65 (P < 0.05), and inhibited the phosphorylation of PI3K and AKT as well as the activation of NF-κB in the ovaries (P < 0.01), thereby ameliorating mild chronic inflammatory damage. Furthermore, SO was found to inhibit the PI3K/AKT signaling pathway by up-regulating the expressions of miRNA-21, miRNA-132, miR-136-5p and miRNA-320, thereby reducing the expression of TLR4/PI3K/AKT/NF-κB axis-related proteins and the release of inflammatory factors.