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.

脑缺血再灌注（IR）是脑卒中后主要的病理生理过程，可严重损害神经功能。汉黄芩素是从黄芩根中提取的天然黄酮类化合物，具有有效的抗炎特性。在这项研究中，我们研究了汉黄芩素通过腺苷5'-单磷酸激活蛋白激酶（AMPK）对大脑中动脉闭塞（MCAO）和氧糖剥夺/复氧（OGD/R）模型诱导的脑IR损伤的保护机制。 /sirtuin 1 (SIRT1)/NOD 样受体家族pyrin 结构域包含3 (NLRP3) 炎性体轴。我们的结果表明，汉黄芩素（20 mg/kg，腹腔注射）可有效减少梗塞面积，减轻脑水肿，改善神经功能缺损，并减轻组织病理学损伤。此外，汉黄芩素可减少脑IR损伤后脑组织和血清中的小胶质细胞活化和炎症因子，包括肿瘤坏死因子α（TNF-α）、白介素-1β（IL-1β）、IL-6和IL-10 。汉黄芩素还有效激活 AMPK/SIRT1 信号通路，并抑制脑 IR 损伤以及 OGD/R 刺激的 HT-22 细胞中 NLPR3 炎性体相关分子的上调。此外，AMPK 抑制剂化合物 C 对 AMPK/SIRT1 信号通路的抑制显着逆转了汉黄芩素对 OGD/R 诱导的 NLRP3 炎性体的保护作用。同时，在化合物C存在下，汉黄芩素对脑IR损伤的保护作用也被逆转。这些结果表明，汉黄芩素通过AMPK/SIRT1信号通路抑制NLRP3炎性体，从而改善脑IR损伤诱导的炎症。