Senkyunolide A Relieves Mammary Inflammatory Damage Through Suppressing Inflammasome-Dependent Pyroptosis and Balancing Mitophagy

Mastitis leads to mammary lesions driven by severe inflammation, oxidative stress and disrupted epithelial barriers.Senkyunolide A (SenA), an active phthalide from Ligusticum chuanxiong, possesses anti-inflammatory activity, but its mechanism against mastitis remains undefined.We investigated SenA's protective effects via inflammatory mammary injury models and HC11 mammary epithelial cells challenged with H2O2.Transcriptomic and proteomic screening pinpointed disturbed pyroptosis and mitophagy pathways in inflamed mammary tissue to guide mechanistic assays.In inflammatory mammary tissue, SenA at two dosages alleviated oedema, suppressed pro-inflammatory cytokines and oxidative indicators, boosted anti-inflammatory and antioxidant levels, and recovered intact breast acini morphology.SenA blocked NLRP3 inflammasome-triggered pyroptosis, regulated PINK1/Parkin-dependent mitophagy, and upregulated ZO-1, occludin and claudin-3 to restore epithelial barrier integrity.In epithelial cells, SenA dose-dependently reduced H2O2 induced cell leakage and pyroptosis.In summary, SenA alleviates mammary inflammatory damage through synergistic modulation of mitophagy, inflammasome-mediated pyroptosis and epithelial barrier function.