Unveiling the mechanisms of Inonotus hispidus against polycystic ovary syndrome: An integrated metabolomics and network pharmacology approach in vivo and vitro

Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by metabolic dysfunction. The research is the first to investigate the therapeutic effect of I. hispidus on polycystic ovarian syndrome (PCOS) based on non-targeted metabolomics and network pharmacology in vivo and vitro. The induction of the rat PCOS model was achieved using testosterone propionate (TP) to evaluate the therapeutic effects of I. hispidus. Firstly, in vivo experiments showed that water extracts from I. hispidus (WE) significantly alleviated ovarian damage in PCOS rats and regulated serum hormone levels. Subsequently, untargeted metabolomics research found that WE may alter the serum metabolome of rats by affecting the metabolism of arginine and proline. Network pharmacology screened multiple chemical components and selected one of the key active ingredient, coniferaldehyde (CON), for validation in vitro cell experiments. Furthermore, treatment with WE, CON and the WE medicated serum (WMS) significantly promoted cell proliferation， and diminished both the levels of reactive oxygen species (ROS) and the apoptosis of KGN cells triggered by testosterone. Meanwhile, all drug interventions significantly regulate the expression of multiple target proteins. However, WMS has the most significant effect. These findings systematically reveal that I. hispidus exerts effects in ameliorating PCOS through multiple targets and multiple components, providing new insights into the mechanism of action of I. hispidus in treating PCOS. In summary, this study accentuates the potential of I. hispidus as a therapeutic agent for PCOS, elucidates a multitarget pharmacological mechanism, provides an experimental basis for subsequent preclinical exploration of Inonotus hispidus in PCOS intervention.