Cordyceps polysaccharide improves polycystic ovary syndrome by inhibiting gut-derived LPS/TLR4 pathway to attenuates insulin resistance

Polycystic ovary syndrome (PCOS) is an endocrine disorder marked by aberrant glucose metabolism and reproductive dysfunction. It is characterized by polycystic ovaries, ovulatory dysfunction, and hyperandrogenemia. PCOS patients often experience a persistent, mild inflammation linked to various metabolic issues and insulin resistance (IR). Cordyceps polysaccharide (CP), extracted from the asexual form of the fungus Cordyceps gunnii, Hirsutella sinensis, is a bioactive crude polysaccharide with triple helix structure. CP was a spherical molecular polymer composed of rhamnose, arabinose, aminoglucose hydrochloride, galactose, glucose, and mannose, and has two molecular weights, 156.511 and 27.298 kDa. Our results corroborated that CP improve polycystic lesions in ovarian tissue and regulates hormone levels and the estrous cycle in rats with PCOS. However, the mechanism of action of this therapy in the treatment of polycystic ovary syndrome is not clear. In the present study, CP was found to modulates disturbances in glucose-lipid metabolism in model rats. In addition, it modulated gut microbiota by decreasing abundance of Gram-negative bacteria (norank_f__Desulfovibrionaceae, Helicobacter), hereby inhibiting the production and transfer of LPS into the systemic circulation. This suppressed the TLR4/MyD88/NF-κB inflammatory pathway in the liver and adipose tissue and restored insulin signaling, which improved IR in PCOS rats. Our findings demonstrate that based on the regulation of gut microbiota disorders and the repair of intestinal barrier damage, CP inhibited the gut-derived LPS/TLR4 inflammatory pathway in liver to attenuated IR, which led to the improvement of ovarian polycystic lesions. In addition, this study tapped into the role of Cordyceps polysaccharides in improving female reproductive function, expanding its clinical application in women with PCOS, which is innovative and offers valuable insights into the therapeutic potential of CP for treating PCOS.