Bazi Bushen Capsule restores fertility by targeting mitochondrial health in aging endometrium.

Age-related decline in endometrial function is a major cause of fertility issues in women, but effective treatments are lacking. This study aimed to investigate the impact of Bazi Bushen Capsule (BZBS) on endometrial aging and its underlying mechanisms. Using naturally aged mice and d-galactose-induced senescent human endometrial stromal cell lines, along with primary human endometrial stromal cells, we explored the effects of BZBS through single-cell RNA sequencing, transcriptome analysis, network pharmacology, and molecular dynamics simulations. Our results showed that BZBS improved endometrial receptivity, and decidualization by activating the AMPK-SIRT3 pathway. The key bioactive components of BZBS were identified as ginsenosides Rb1, Rb2, Rg5, and luteolin. Specifically, luteolin restored mitochondrial homeostasis by regulating PINK1/Parkin-mediated mitophagy and inhibiting Drp1. These findings suggested that BZBS effectively restored endometrial function and offered a promising therapeutic approach to counteract age-related endometrial dysfunction, potentially improving fertility in women of advanced maternal age.