Inflammatory reaction after ischemia-reperfusion contributes significantly to a worsened prognosis, and microglia activation is the main resource of inflammation in the nervous system. Targeting STAT5 has been shown to be a highly effective anti-inflammatory therapy; however, the mechanism by which the STAT5 signaling pathway regulates neuroinflammation following brain injury induced by ischemia-reperfusion remains unclear. Dauricine is an effective agent in anti-inflammation and neuroprotection, but the mechanism by which dauricine acts in ischemia-reperfusion remained unknown. This study is the first to find that the anti-inflammation mechanism of dauricine mainly occurs through the STAT5-NF-κB pathway and that it might act as a STAT5 inhibitor. Dauricine suppresses the inflammation caused by cytokines Eotaxin, KC, TNF-α, IL-1α, IL-1β, IL-6, IL-12β, and IL-17α, as well as inhibiting microglia activation. The STAT5b mutant at Tyr-699 reverses the protective effect of dauricine on the oxygen-glucose deprivation-reperfusion injury of neurons and reactivates the P-NF-κB expression in microglia. These results suggest that dauricine might be able to suppress the neuroinflammation and protect the neurons from the injury of post-ischemia-reperfusion injury via mediating the microglia activation through the STAT5-NF-κB pathway. As a potential therapeutic target for neuroinflammation, STAT5 needs to be given further attention regarding its role in ischemic stroke.
Keywords: NF-κB; STAT5; dauricine; inflammation; ischemia-reperfusion injury.