Taohong Siwu decoction mitigates abnormal uterine bleeding by suppressing ferroptosis in endometrial epithelial cell through p38MAPK signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Abnormal uterine bleeding (AUB) represents a prevalent gynecological disease. Taohong Siwu Decoction (TSD), a classic formula originating from the Qing Dynasty medical text "Yizong Jinjian", is clinically known to promote blood circulation and resolve blood stasis. Although this formula is extensively employed for managing gynecological diseases associated with postpartum blood stasis syndrome, its underlying therapeutic mechanism remains incompletely understood.

AIM OF THE STUDY: This study aims to investigate the mechanism by which p38MAPK signaling regulates ferroptosis in the context of AUB, and to elucidate the therapeutic mechanism of TSD in treating AUB.

MATERIALS AND METHODS: A rat model of incomplete medical abortion (IMA) was established in vivo to induce AUB, and the Ishikawa cell line was used for assessing the pharmacological effects of TSD on ferroptosis in vitro. We employed transcriptomic analysis to predict the underlying mechanism by which TSD treats AUB induced by IMA. We used p38MAPK inhibitors and activators in Ishikawa cells to examine how this pathway mediates ferroptosis and to determine the impact of TSD on this regulation.

RESULTS: TSD shortened the duration of uterine bleeding, decreased the bleeding volume, and lowered the levels of inflammatory factors. Integrated analysis systematically demonstrates that TSD exerts its therapeutic effect on AUB induced by IMA by inhibiting ferroptosis. Transcriptome analysis revealed that the MAPK signaling pathway is pivotal for ameliorating AUB induced by IMA. Western blot and immunohistochemistry verified that TSD significantly inhibits ferroptosis via the p38MAPK pathway in both settings.

CONCLUSION: These results suggest that TSD treats AUB induced by IMA by inhibiting ferroptosis through the p38MAPK signaling pathway.