Isorhapontigenin ameliorates cerebral ischemia/reperfusion injury via modulating Kinase Cε/Nrf2/HO‐1 signaling pathway

• Main Authors: Zhe Xue, Kai Zhao, Zhenghui Sun, Chen Wu, Bowen Yu, Dongsheng Kong, Bainan Xu
• Format: Article
• Language: English
• Published: Wiley 2021-07-01
• Series: Brain and Behavior
• Subjects: cerebral ischemia; HO‐1; isorhapontigenin; Nrf2; oxidative stress; PKCε
• Online Access: https://doi.org/10.1002/brb3.2143

Abstract Background Isorhapontigenin (ISO) has been shown to have antioxidant activity. This study aimed to investigate the antioxidant effects of ISO on cerebral ischemia/reperfusion (I/R) injury and its possible molecular mechanisms. Methods Focal cerebral ischemia‐reperfusion injury (MCAO/R) model and primary cortical neurons were established an oxygen‐glucose deprivation (OGD / R) injury model. After 24 hr of reperfusion, the neurological deficits of the rats were analyzed and HE staining was performed, and the infarct volume was calculated by TTC staining. In addition, the reactive oxygen species (ROS) in rat brain tissue, the content of 4‐Hydroxynonenal (4‐HNE), and 8‐hydroxy2deoxyguanosine (8‐OHdG) were detected. Neuronal cell viability was determined by MTT assay. Western blot analysis was determined for protein expression. Results ISO treatment significantly improved neurological scores, reduced infarct volume, necrotic neurons, ROS production, 4‐HNE, and 8‐OHdG levels. At the same time, ISO significantly increased the expression of Nrf2 and HO‐1. The neuroprotective effects of ISO can be eliminated by knocking down Nrf2 and HO‐1. In addition, knockdown of the PKCε blocked ISO‐induced nuclear Nfr2, HO‐1 expression. Conclusion ISO protected against oxidative damage induced by brain I/R, and its neuroprotective mechanism may be related to the PKCε/Nrf2/HO‐1 pathway.