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.

To Cite This Article: Ji M, Chen J, Fu Y, He Q, Sui J, Bi W, Dai F, Gu X, Kandeel M, Dong S and Qu W, 2026. Senkyunolide a relieves mammary inflammatory damage through suppressing inflammasome-dependent pyroptosis and balancing mitophagy. Pak Vet J, 2026, 46(10): 2591-2600. http://dx.doi.org/10.29261/pakvetj/2026.248