Baicalin promotes antibacterial defenses by modulating mitochondrial function

Natural flavonoids, such as baicalin, have been extensively studied for their role in bacterial infection. However, the underlying mechanisms remain poorly understood. We demonstrated that baicalin coordinates mitochondrial function and dynamics to promote antibacterial response. Baicalin protected against Staphylococcus aureus infections and alleviates inflammatory responses in vivo and in vitro. An increase in mitochondrial mass and elevated expression of factors regulating mitochondrial fission and fusion were observed in baicalin-treated macrophages. Baicalin induced Drp1-dependent biogenesis, which contributes to the generation of additional mitochondria. Baicalin improved the mitochondrial membrane potential, ATP levels, and mitochondrial reactive oxygen species (mtROS) production. Importantly, the inhibition of mitochondrial function by rotenone or MitoTEMPO suppressed the antimicrobial activity of baicalin in macrophages. We conclude that baicalin can regulate immune responses during S. aureus infection by improving mitochondrial function and dynamics, implying that it is a promising therapeutic agent for controlling infection and inflammatory diseases.