Ferulic acid inhibits LPS-induced apoptosis in bovine mammary epithelial cells by regulating the NF-κB and Nrf2 signalling pathways to restore mitochondrial dynamics and ROS generation

In bovine mammary epithelial cells (BMECs), a cascade of inflammatory reactions induced by lipopolysaccharide (LPS) has been shown to result in cell injury and apoptosis. The present study aims to reveal the protective effect of ferulic acid (FA) on LPS-induced BMEC apoptosis and explore its potential molecular mechanisms. First, we showed that FA had low cytotoxicity to BMECs and significantly decreased cell apoptosis and the proinflammatory response induced by LPS. Next, FA blocked LPS-induced oxidative stress by restoring the balance of the redox state and inhibiting mitochondrial dysfunction, the main contributor to LPS-induced apoptosis and ROS generation. Furthermore, the relief of inflammation and redox disturbance in the FA preconditioning group were accompanied by weaker NF-kappa B activation, enhanced Nrf2 activation and maintained cell viability compared to the LPS group. When BMECs were treated with FA alone, we observed that Nrf2 activation was induced before the inhibition of NF-kappa B activation and that the Keap1-Nrf2 relationship was disturbed. We concluded that FA prevented LPS-induced BMEC apoptosis by reversing the dominant relationship between NF-kappa B and Nrf2.

Automated summary

The study revealed that ferulic acid (FA) has a protective effect on lipopolysaccharide (LPS)-induced bovine mammary epithelial cell (BMEC) apoptosis by restoring redox balance, inhibiting mitochondrial dysfunction, reducing oxidative stress, decreasing NF-kappa B activation, enhancing Nrf2 activation, and maintaining cell viability. Treatment with FA alone showed induction of Nrf2 activation before inhibition of NF-kappa B activation, suggesting that FA may prevent BMEC apoptosis by reversing the dominant relationship between NF-kappa B and Nrf2.