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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.
This study demonstrated in vivo that baicalin effectively alleviates mastitis symptoms in dairy cows and mice, primarily manifested by reduced tissue pathological damage, decreased levels of pro-inflammatory cytokines, and maintain the integrity of the blood-milk barrier (BMB). Multi-omics sequencing analysis indicated that IL-17 and TNF signaling pathways play crucial roles in this process. Further studies demonstrated that IL-17RA-/- 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.
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.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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