Takinib inhibits microglial M1 polarization and oxidative damage after subarachnoid hemorrhage by targeting TAK1-dependent NLRP3 inflammasome signaling pathway
Transforming growth factor-ß-activated kinase 1 (TAK1) positively regulates oxidative stress and inflammation in various illnesses. Takinib, a singular and particular TAK1 inhibitor, has advantageous effects in a number of disorders. However, the results of takinib on early brain injuries (EBI) after subarachnoid hemorrhage (SAH) and also the underlying molecular mechanisms remain unknown. Our study demonstrated that takinib administration considerably inhibited phosphorylated TAK1 expression after SAH. Additionally, takinib covered up M1 microglial polarization and promoted M2 microglial polarization. In addition, blockade of TAK1 by takinib reduced neuroinflammation, oxidative damage, brain edema, and neuronal apoptosis, and improved nerve behavior after SAH. Mechanistically, we says TAK1 inhibition by takinib mitigated reactive oxygen species (ROS) production and ROS-mediated nod-like receptor pyrin domain-that contains protein 3 (NLRP3) inflammasome activation. In comparison, NLRP3 activation by nigericin abated the neuroprotective results of takinib against EBI after SAH. Generally, our study shown that takinib could safeguard against EBI by targeting TAK1-ROS-NLRP3 inflammasome signaling. Inhibition of TAK1 may well be a promising option in the treating of SAH.