Formononetin protects against inflammation associated with cerebral ischemia-reperfusion injury in rats by targeting the JAK2/STAT3 signaling pathway
Formononetin protects against inflammation associated with cerebral ischemia-reperfusion injury in rats by targeting the JAK2/STAT3 signaling pathway
复制标题
芒柄花素通过靶向 JAK2/STAT3 信号通路预防大鼠脑缺血再灌注损伤相关炎症
DOI：
10.1016/j.biopha.2022.112836
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发表时间：
2022-03-24
影响因子：
7.5
通讯作者：
Yang, Jiehong
中科院分区：
文献类型：
--
作者：
Yu, Li;Zhang, Yangyang;Yang, Jiehong
背景：芒柄花素是从中药红三叶草中提取的一种植物雌激素。它具有抗肿瘤、肝脏保护和神经保护特性。但芒柄花素在脑缺血再灌注损伤中的抗炎作用尚未见报道。目的：探讨芒柄花素在脑缺血再灌注损伤中JAK2/STAT3信号通路的潜在作用机制。方法：采用雄性SD大鼠建立大脑中动脉闭塞（MCAO）模型，随机分为5组：Sham组、MCAO组、JAK2组。抑制剂 (Ag490)、芒柄花素、抑制剂 + 芒柄花素。通过神经功能缺损试验、TTC染色、H&E染色、尼氏染色、ELISA、RT-PCR、蛋白质印迹和免疫荧光检测芒柄花素对MCAO大鼠的保护作用。结果：芒柄花素显着减轻神经功能缺损和脑组织病理状态，减少脑梗死体积、血浆IL-18和TNF-α炎症因子水平、IL-6和IL-6 mRNA水平。大鼠脑组织中IL-1β，以及MCAO大鼠脑组织中p-JAK2、p-STAT3、NLRP3、ASC、cl-Caspase-1、cl-IL-1β蛋白水平。结论：芒柄花素具有抗炎作用。可能抑制JAK2/STAT3信号通路中的相关靶点，从而对脑缺血再灌注损伤具有一定的保护作用。
Background: Formononetin is a type of phytoestrogen obtained from the Chinese medical herb Red Clover. It exhibits anti-neoplastic hepatoprotective, and neuroprotective properties. However, the anti-inflammatory effect of formononetin in cerebral ischemia-reperfusion injury has not been reported.& nbsp;Objective: To explore the potential mechanism of action of formononetin in cerebral ischemia-reperfusion injury with regard to the JAK2/STAT3 signaling pathway.& nbsp;Methods: Male SD rats were used to establish a middle cerebral artery occlusion (MCAO) model and randomly divided into 5 groups: Sham, MCAO, JAK2 Inhibitor (Ag490), Formononetin, Inhibitor + Formononetin. The protective effect of formononetin in MCAO rats was detected by performing neurological deficit testing, TTC staining, H & E staining, Nissl staining, ELISA, RT-PCR, western blotting and immunofluorescence.& nbsp;Results: Formononetin significantly alleviated the neurological deficit and the pathological state of brain tissues, and reduced the volume of cerebral infarction, levels of IL-18 and TNF-alpha inflammatory factors in plasma, mRNA levels of IL-6 and IL-1 beta in rat brain tissue, and the protein levels of p-JAK2, p-STAT3, NLRP3, ASC, cl-Caspase-1, and cl-IL-1 beta in the MCAO rat brain tissue.& nbsp;Conclusion: Formononetin has anti-inflammatory effects. It may inhibit the relevant targets in the JAK2/STAT3 signaling pathway, thereby having a certain protective effect against cerebral ischemia-reperfusion injury.