Cepharanthine Reduces Endometriosis Lesions and Alters Mitochondrial and Autophagy-Related Signals in Endometriotic Stromal Cells

Endometriosis is a chronic inflammatory disorder characterized by the ectopic growth of endometrial-like tissue, leading to pelvic pain and infertility. Although cepharanthine has well-established anti-inflammatory properties, its therapeutic potential and underlying mechanisms in endometriosis remain largely unexplored. In this study, the effects of cepharanthine were evaluated using a surgically induced mouse model and immortalized human endometrial stromal cell models. Cepharanthine treatment significantly reduced the calculated lesion volume, whereas wet lesion weight did not differ significantly between the groups. Cepharanthine was also accompanied by reduced spleen weight and alterations in the CD4+ helper T-cell population in vivo. In immortalized human ovarian endometriotic stromal cells (ihOESCs), cepharanthine significantly decreased cell viability, induced apoptosis, and disrupted cell-cycle progression. Cepharanthine altered autophagy-related signaling, accompanied by increased acidic vesicle-associated signals and accumulation of LC3B-II and p62/SQSTM1; however, the direction of autophagic flux remains unclear. These changes were associated with elevated reactive oxygen species production, intracellular Ca2+ redistribution, and mitochondrial dysfunction. Collectively, these findings indicate that cepharanthine reduces calculated lesion volume in vivo and alters mitochondrial function, autophagy-related signaling, apoptosis and cell-cycle progression in ihOESCs, supporting its potential as a therapeutic candidate.