Parthenolide Relieves LPS-Induced Mammary Damage by Regulating Inflammation, Apoptosis, and BloodMilk Barrier in Mice

Mastitis is a common disease in dairy cows, characterized primarily by mammary inflammation, which induces epithelial cell apoptosis and blood–milk barrier (BMB) disruption, seriously threatening milk quality and yield. Parthenolide (PTL), a bioactive sesquiterpene lactone, exhibits anti-inflammatory and antibacterial properties. However, its effectiveness in treating mastitis has not yet been conclusively proven. In this study, we established an in vivo mouse model to investigate the mechanisms underlying the protective effects of PTL on LPS-induced mammary gland damage. HE staining and TEM showed that PTL (10 mg/kg) alleviated LPS-induced histopathological and ultrastructural damage in mouse mammary tissues. To be specific, PTL suppressed the LPS-induced increase in the p-NF-κB/NF-κB ratio and IL-1β, IL-6, and TNF-α mRNA levels, indicating that PTL inhibits inflammation via the NF-κB signaling pathway. In addition, PTL also reduced TUNEL-positive cells and the p-p53/p53 ratio, Bax/Bcl-2 ratio, and protein levels of cytochrome c and caspase-3, indicating that PTL inhibited p53-dependent mitochondria-mediated apoptosis in LPS-exposed of mouse mammary tissues. Furthermore, PTL reversed BMB hyperpermeability and the upregulation of MLCK and p-MLC proteins, restored the expression of tight junction (TJ) proteins Claudin-3, occludin, and ZO-1, and corrected ZO-1 distribution abnormalities, indicating that PTL mitigates LPS-induced BMB disruption by regulating MLCK signaling in mouse mammary tissues. In summary, PTL relieves LPS-induced mammary damage in mice by regulating inflammation, apoptosis, and the BMB, which is associated with the inhibition of the NF-κB-p53/MLCK signaling pathway.