Astragaloside IV alleviates chronic low-grade inflammation in polycystic ovary syndrome by acting on IL-6R and inhibiting the NLRP3 inflammasome.

PCOS is a common endocrine and metabolic disorder. Chronic low-grade inflammation plays a significant role in its pathogenesis, although the precise underlying mechanisms remain incompletely understood. AS-IV, the main active constituent of Astragalus membranaceus, exhibits various pharmacological activities, including anti-inflammatory and metabolic regulatory effects. However, its specific mechanisms of action in PCOS require further investigation. This study aimed to explore the potential mechanism by which AS-IV improves PCOS by modulating inflammatory pathways, using an integrated approach combining network pharmacology, molecular docking, and in vitro experiments. Potential common targets of AS-IV and PCOS were screened by integrating multiple database resources. KEGG/GO enrichment analysis and machine learning algorithms (LASSO, RF and SVM) were employed to identify core targets. Molecular docking was performed to evaluate the binding potential of AS-IV to the core target. Finally, using a testosterone-induced PCOS cell model, the effect of AS-IV on the expression of key inflammatory proteins was validated by Western blot. A total of 275 common targets of AS-IV and PCOS were identified through comprehensive analysis. Machine learning screening pinpointed IL6R as a potential core target. Molecular docking results indicated a binding energy of −6.7 kcal/mol between AS-IV and IL6R, suggesting a plausible interaction. In vitroexperiments demonstrated that AS-IV treatment significantly reduced the expression levels of key inflammation-related proteins, including IL6R, NLRP3, NF-κB p65, p38 MAPK, and TNF-α, in the PCOS cell model. AS-IV may alleviate chronic low-grade inflammation associated with PCOS by acting on IL6R and inhibiting the NLRP3 inflammasome.