Zhang Yuqin, Qiao Lifei, Xu Wen, Wang Xiaoying, Li Huang, Xu Wei, Chu Kedan, Lin Yu
College of Pharmacy of Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
Molecules. 2017 Feb 27;22(3):359. doi: 10.3390/molecules22030359.
Paeoniflorin (PF) is an active ingredient of Paeoniae Radix which possesses the neuroprotective effect. However, so far, the neuroprotective mechanism of PF has still not been fully uncovered. The Ca/Ca/calmodulin-dependent protein kinase II (CaMKII)/cAMP response element-binding (CREB) signaling pathway plays an important role in the intracellular signal transduction pathway involved in cell proliferation, cell survival, inflammation and metabolism. Herein, the neuroprotective roles of PF in the models of middle cerebral artery occlusion (MCAO) followed by reperfusion in rats and -methyl-d-aspartic acid (NMDA)-induced excitotoxicity in primary hippocampal neurons were investigated. Moreover, we attempted to confirm the hypothesis that its protection effect is via the modulation of the Ca/CaMKI)/CREB signaling pathway. In this study, PF not only significantly decreased neurological deficit scores and infarct volume in vivo, but also improved neurons' cell viability, and inhibited neurons' apoptosis and intracellular Ca concentration in vitro. Furthermore, PF significantly up-regulated p-CREB and p-CaMKII, and down-regulated calmodulin (CaM) in vivo and in vitro. The results indicate that the protective effect of PF on cerebral ischemia reperfusion injury is possible through regulating the Ca/CaMKII/CREB signaling pathway.
芍药苷（PF）是芍药根的一种活性成分，具有神经保护作用。然而，迄今为止，PF的神经保护机制尚未完全阐明。钙/钙调蛋白依赖性蛋白激酶II（CaMKII）/环磷酸腺苷反应元件结合蛋白（CREB）信号通路在涉及细胞增殖、细胞存活、炎症和代谢的细胞内信号转导通路中起重要作用。在此，研究了PF在大鼠大脑中动脉闭塞（MCAO）再灌注模型和原代海马神经元中N-甲基-D-天冬氨酸（NMDA）诱导的兴奋性毒性模型中的神经保护作用。此外，我们试图证实其保护作用是通过调节Ca/CaMKII/CREB信号通路这一假设。在本研究中，PF不仅显著降低了体内神经功能缺损评分和梗死体积，还提高了体外神经元的细胞活力，抑制了神经元凋亡和细胞内钙浓度。此外，PF在体内和体外均显著上调p-CREB和p-CaMKII，并下调钙调蛋白（CaM）。结果表明，PF对脑缺血再灌注损伤的保护作用可能是通过调节Ca/CaMKII/CREB信号通路实现的。
