Irisolidone Ameliorates Cyclophosphamide-Induced POI via Inhibiting Inflammatory Response

Premature ovarian insufficiency (POI) is a condition marked by diminished ovarian function and reduced fertility, caused by the chemotherapy drug cyclophosphamide (CTX) used to treat gynecologic cancers. The abnormal inflammation of ovarian tissue induced by CTX represents a key factor that impairs follicular cells and disrupts fertility. Therefore, the present study aims to investigate the underlying mechanisms of CTX-induced abnormal ovarian inflammation and identify potential therapeutic agents.

RNA sequencing data derived from CTX-induced mouse ovarian tissues were first intersected with inflammation-related genes retrieved from the Gene Ontology (GO) database. This was followed by functional enrichments analysis and protein-protein interaction (PPI) analyses to identify target genes. Subsequently, the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was screened to obtain corresponding candidate therapeutic agents. Finally, a CTX-induced mouse model was established to verify the therapeutic efficacy of the candidate drug and elucidates its underlying mechanisms.

A total of 25 candidate genes were identified, with interleukin 1β (IL1β) confirmed as the core gene. Subsequent screening resulted in the identification of Irisolidone as a potential therapeutic agent. The present study demonstrated that Irisolidone ameliorates CTX-induced follicular cell developmental impairment and improves fertility in mice with POI. Mechanistically, it was found that Irisolidone suppressed abnormal ovarian inflammation by inhibiting the CTX-disrupted nuclear factor kappa B (NFκB)/NOD-like receptor pyrin domain-containing 3 (NLRP3)/Caspase1 signaling pathway.

The present study demonstrates that Irisolidone can effectively alleviate CTX-induced POI by inhibiting abnormal inflammation. These findings suggest that Irisolidone holds promise as a novel therapeutic candidate for POI, thereby providing a potential new treatment strategy for clinical management of this condition.