Resveratrol alleviates oxidative stress caused by Streptococcus uberis infection via activating the Nrf2 signaling pathway.

Due to its antioxidant properties, resveratrol may relieve the cellular oxidative injury induced by Streptococcus uberis (S. uberis) infection. However, the underlying molecular mechanisms remain unknown. Herein, we used S. uberis to challenge C57BL/6 mice or a mouse mammary epithelial cell line (EpH4-Ev), and the regulatory molecular mechanism of resveratrol on hosts' oxidative injury were investigated. The results showed that gavage of resveratrol alleviate the inflammatory responses and oxidative injury of mammary gland tissues induced by S. uberis infection via activating Nrf2 signaling pathways. To further understand the molecular mechanism, inhibitor of Nrf2 (ML385) and siRNA targeting p62 were used in mammary epithelial cells. The findings indicated that resveratrol mediates Keap1 degradation by activating p62, induces the expression of Nrf2 and its downstream antioxidant signaling pathways, and ameliorates oxidative damage during S. uberis infection. Collectively, these outcomes suggested that resveratrol can function as an activator of the p62-Keap1/Nrf2 signaling pathway to improve oxidative injury caused by S. uberis in mammary glands as well as in EpH4-Ev cells. Therefore, resveratrol may be useful to prevent and control S. uberis-induced bovine mastitis by relieving oxidative stress.