Activation of Sirtuin‐1 by Pinocembrin Treatment Contributes to Reduced Early Brain Injury after Subarachnoid Hemorrhage
Yile Zeng, Zhongning Fang, Jinqing Lai, Zhe Wu, Weibin Lin, Hao Yao, Weipeng Hu, Junyan Chen, Xieli Guo, Xiangrong Chen
Abstract
Subarachnoid hemorrhage (SAH) as a devastating neurological disorder is closely related to heightened oxidative insults and neuroinflammatory injury. Pinocembrin, a bioflavonoid, exhibits different biological functions, such as immunomodulatory, anti‐inflammatory, antioxidative, and cerebroprotective activities. Herein, we examined the protective effects and molecular mechanisms of pinocembrin in a murine model of SAH. Using an endovascular perforation model in rats, pinocembrin significantly mitigated SAH‐induced neuronal tissue damage, including inflammatory injury and free‐radical insults. Meanwhile, pinocembrin improved behavior function and reduced neuronal apoptosis. We also revealed that sirtuin‐1 (SIRT1) activation was significantly enhanced by pinocembrin. In addition, pinocembrin treatment evidently enhanced peroxisome proliferator‐activated receptor‐ γ coactivator expression and suppressed ac‐nuclear factor‐kappa B levels. In contrast, EX‐527, a selective SIRT1 inhibitor, blunted the protective effects of pinocembrin against SAH by suppressing SIRT1‐mediated signaling. These results suggested that the cerebroprotective actions of pinocembrin after SAH were through SIRT1‐dependent pathway, suggesting the potential application of pinocembrin for the treatment of SAH.