AUTHOR=Ni Weiming , Wu Xiaoqin , Feng Li , Xu Min , Tian Yingzhou 

TITLE=Curcumol alleviates endometriosis via correcting the aberrant activation of Fas/RIPK1-mediated PANoptosis

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1691279

DOI=10.3389/fphar.2025.1691279

ISSN=1663-9812

ABSTRACT=Endometriosis (EMs) is an estrogen-dependent chronic inflammatory disease. While apoptosis resistance (evidenced by Bcl-2 upregulation and Bax/caspase-3 downregulation) remains a hallmark of EMs, recent studies reveal a paradoxical coexistence of aberrant apoptotic activation (Fas/FADD/Caspase-8) and inflammatory PANoptosis in ectopic lesions, suggesting novel therapeutic targets for this complex disorder. GEO database mining revealed PANoptosis-related genes in EMs, which was experimentally validated through clinical and animal studies demonstrating the critical role of Fas/FADD/Caspase-8/RIPK1 signaling. Curcumol, the active component of Curcuma zedoaria rhizomes, exhibited strong binding affinity to Fas/RIPK1 in molecular docking and dynamics simulations, and effectively alleviated EMs progression by modulating this pathway, providing novel therapeutic insights for EMs management.