Baicalin alleviates mastitis in dairy cows by targeting IL-17RA to inhibit IL-17 signaling pathway activation

BACKGROUND: Mastitis, one of the most prevalent inflammatory diseases in female mammals, causes significant economic losses in livestock farming. Notably, the natural flavonoid compound baicalin exhibits potent anti-inflammatory activity. However, its efficacy in alleviating mastitis severity and the underlying molecular mechanisms remain unexplored. Therefore, this study aims to investigate the protective effects of baicalin in alleviating mastitis and its key molecular mechanisms. RESULTS: mice exhibited a phenotype similar to that observed with baicalin treatment, confirming the importance of this pathway. Notably, network pharmacology screening combined with molecular dynamics simulations revealed stable binding of baicalin to IL-17RA, suggesting that baicalin exerts its protective effect to alleviate mastitis by targeting IL-17RA. Mechanistically, both baicalin treatment and IL-17RA deletion block activation of key downstream pathways of the IL-17 signaling pathway, including MAPK, ERK and NF-κB, thereby suppressing excessive activation of the TNF signaling pathway, preventing exacerbation of the inflammatory response and barrier damage. CONCLUSIONS: In conclusion, this study demonstrates that baicalin inhibits excessive activation of the IL-17/TNF signaling pathway by targeting IL-17RA, thereby reducing inflammatory responses and BMB damage within the mammary gland and alleviating mastitis severity.