Sinomenine protects mice against Staphylococcus aureus-induced endometritis through inhibition of P2X7 receptor-mediated ferroptosis and inflammation.

Endometritis is a major cause of infertility that adversely impacts both human reproductive health and livestock productivity. This study investigated the protective effects and underlying mechanisms of sinomenine (SIN) against Staphylococcus aureus (S. aureus)-induced endometritis. Seventy-two adult female mice were randomly divided into six groups: control group, SIN group (100 mg/kg), S. aureus group (1 × 107 CFU per 200 μL PBS), and SIN (25 mg/kg, 50 mg/kg, and 100 mg/kg, respectively) + S. aureus groups. Uterine tissues were collected for analysis. Inflammatory factors, ferroptosis, and P2X7 signaling pathway-associated proteins were detected. S. aureus infection induced severe uterine pathology, significantly elevating myeloperoxidase (MPO) activity and pro-inflammatory cytokine levels (TNF-α, IL-1β, and IL-6; P < 0.05). Infection also triggered ferroptosis and upregulated P2X7 pathway components (P < 0.05). SIN administration dose-dependently attenuated these pathological changes, reversing endometritis severity (P < 0.05). These findings demonstrate that SIN alleviates S. aureus-induced endometritis by suppressing P2X7 receptor-mediated ferroptosis, providing a mechanistic rationale for its therapeutic potential.IMPORTANCEWe demonstrated for the first time that SIN could protect mice against S. aureus-induced endometritis. The mechanism was through inhibition of P2X7 receptor-mediated ferroptosis, which provides a theoretical basis for SIN treatment of endometritis.