Streptococcus equi subsp . zooepidemicus (SEZ) is a zoonotic bacterial pathogen that causes life-threatening infections and various diseases such as meningitis, endocarditis and pneumonia. With the use of antibiotics being severely restricted in the international community, an alternative to antibiotics is urgently needed against bacterial. In the present study, the herbal extract magnolol protected mice against SEZ infection, reflected by increased survival rate and reduced bacterial burden. A pro-inflammatory form of cell death occurred in SEZ-infected macrophage. Magnolol downregulated the expression of pyroptosis-related proteins and reduced the formation of cell membrane pores in infected macrophages to suppress the development of subsequent inflammation. We further demonstrated that magnolol directly suppressed SEZ-induced macrophage pyroptosis, which partially protected macrophages from SEZ infection. Our study revealed that magnolol suppressed inflammation and protected mice against SEZ infection, providing a possible treatment for SEZ infection.
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