Abstract
Cerebral ischemia-reperfusion (IR) is the main pathophysiological process after stroke and can seriously impair neurological function. Wogonin, a natural flavonoid extracted from the roots of Scutellaria baicalensis, has potent anti-inflammatory properties. In this study, we investigated the protective mechanism of wogonin against middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) model-induced cerebral IR injury through adenosine 5'-monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome axis. Our results showed that wogonin (20 mg/kg, intraperitoneal injection) effectively reduced infarct size, attenuated brain edema, improved neurological deficits, and alleviated histopathological damage. In addition, wogonin reduced microglial cell activation and inflammatory factors, including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, and IL-10, in brain tissue and serum after cerebral IR injury. Wogonin also effectively activated the AMPK/SIRT1 signaling pathway and inhibited NLPR3 inflammasome-related molecules upregulation in cerebral IR injury as well as in OGD/R-stimulated HT-22 cells. Furthermore, inhibition of the AMPK/SIRT1 signaling pathway by Compound C, an AMPK inhibitor, significantly reversed the protective effect of wogonin on OGD/R-induced NLRP3 inflammasome. Meanwhile, the protective effect of wogonin against brain IR injury was also reversed in the presence of compound C. These results suggest that wogonin ameliorates cerebral IR injruy-induced inflammation by inhibiting NLRP3 inflammasome through the AMPK/SIRT1 signaling pathway.