Calenduloside E (CE) isolated from Aralia elata (Miq.) Seem. is a natural triterpenoid saponin that can reportedly ameliorate myocardial ischemia/reperfusion injury. However, its potential roles and mechanism in cerebral ischemia/reperfusion injury are barely understood. In this study, we established an oxygen-glucose deprivation/reoxygenation (OGD/R) model in HT22 cells. We found that CE significantly attenuated the OGD/R-induced inhibition of cell viability and apoptotic cell death in HT22 cells. Moreover, CE treatment significantly ameliorated OGD/R-induced mitochondrial fission by inhibiting mitochondrial dynamin-related protein 1 (Drp1) recruitment and increasing Drp1 phosphorylation at Ser637. CE treatment significantly ameliorated OGD/R-induced mitochondrial dysfunction by increasing the mitochondrial membrane potential and reducing the mitochondrial ROS and cellular calcium accumulation. Moreover, CE treatment significantly inhibited the OGD/R-induced release of mitochondrial Cytochrome C and increase in Bax, Cleaved-caspase3 and Cleaved-caspase9 protein levels, whereas CE treatment significantly reversed the OGD/R-induced decrease in Bcl-2 and full length of caspase3 and caspase9 protein levels. In vivo, we found that CE treatment significantly ameliorated ischemic/hypoxic-induced brain infarct volume, neurological deficits, and neuronal apoptosis in mice after middle cerebral artery occlusion and reperfusion. CE treatment also significantly ameliorated the mitochondrial transmembrane potential, decreased Cytochrome C release, and reversed the increase in Bax, Cleaved-caspase3 and Cleaved-caspase9 protein levels and the decrease in Bcl-2 and full length of caspase3 and caspase9 protein levels induced by cerebral ischemia/reperfusion (I/R). All these results indicated that CE treatment exerted a neuroprotective effect by ameliorating mitochondrial dysfunction during cerebral I/R injury.

金盏花苷 E (CE) 从龙牙竹中分离出来（米克）看来。是一种天然三萜皂甙，据报道可以改善心肌缺血/再灌注损伤。然而，其在脑缺血/再灌注损伤中的潜在作用和机制尚不清楚。在这项研究中，我们在 HT22 细胞中建立了氧-葡萄糖剥夺/复氧 (OGD/R) 模型。我们发现 CE 显着减弱了 OGD/R 诱导的 HT22 细胞中细胞活力和凋亡细胞死亡的抑制作用。此外，CE 治疗通过抑制线粒体动力相关蛋白 1 (Drp1) 募集和增加 Ser637 位点的 Drp1 磷酸化，显着改善了 OGD/R 诱导的线粒体裂变。CE 治疗通过增加线粒体膜电位和减少线粒体 ROS 和细胞钙积累来显着改善 OGD/R 诱导的线粒体功能障碍。此外，CE 处理显着抑制 OGD/R 诱导的线粒体细胞色素 C 释放和 Bax、Cleaved-caspase3 和 Cleaved-caspase9 蛋白水平的增加，而 CE 处理显着逆转 OGD/R 诱导的 Bcl-2 和全caspase3 和 caspase9 蛋白水平的长度。在体内，我们发现 CE 治疗显着改善了大脑中动脉闭塞和再灌注后小鼠缺血/缺氧诱导的脑梗死体积、神经功能缺损和神经元凋亡。CE 处理还显着改善了线粒体跨膜电位，减少了细胞色素 C 的释放，并逆转脑缺血/再灌注 (I/R) 诱导的 Bax、Cleaved-caspase3 和 Cleaved-caspase9 蛋白水平的增加以及 Bcl-2 和全长 caspase3 和 caspase9 蛋白水平的降低。所有这些结果表明，CE 治疗通过改善脑 I/R 损伤期间的线粒体功能障碍发挥神经保护作用。