Irisolidone Ameliorates Cyclophosphamide-Induced POI via Inhibiting Inflammatory Response

Area of Science:

• Reproductive Biology
• Oncology
• Pharmacology

Background:

• Premature ovarian insufficiency (POI) is a significant side effect of cyclophosphamide (CTX) chemotherapy, leading to infertility.
• CTX-induced ovarian inflammation is a key factor in follicular cell damage and fertility loss.
• Understanding the mechanisms of CTX-induced ovarian inflammation is crucial for developing effective treatments.

Purpose of the Study:

• To elucidate the molecular mechanisms underlying CTX-induced ovarian inflammation.
• To identify potential therapeutic agents for mitigating CTX-induced POI.
• To evaluate the efficacy and mechanism of Irisolidone in a mouse model of POI.

Main Methods:

• RNA sequencing and bioinformatics analyses (GO, PPI) were used to identify key genes in CTX-induced ovarian inflammation.
• The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was screened for candidate drugs.
• A CTX-induced mouse model was established to validate the therapeutic effects of Irisolidone.

Main Results:

• Interleukin 1β (IL1β) was identified as a core gene in CTX-induced ovarian inflammation.
• Irisolidone was identified as a potential therapeutic agent, significantly improving fertility in POI mice.
• Irisolidone suppressed ovarian inflammation by inhibiting the NFκB/NLRP3/Caspase1 signaling pathway.

Conclusions:

• Irisolidone effectively alleviates CTX-induced POI by targeting abnormal ovarian inflammation.
• Irisolidone demonstrates potential as a novel therapeutic candidate for POI.
• These findings offer a new treatment strategy for the clinical management of chemotherapy-induced infertility.