Department of Neonatology, TongJi Hospital, Tongji Medical College, P. R. China.
Department of Biochemistry and Molecular Biology, School of Basic Medicine and the Collaborative Innovation Center for Brain Science, Huazhong University of Science and Technology, Wuhan 430030, Hubei, P. R. China.
Am J Chin Med. 2022;50(4):1133-1153. doi: 10.1142/S0192415X2250046X. Epub 2022 May 5.
Salidroside, an active ingredient in , has potent protective activity against cerebral ischemia. However, the mechanisms underlying its pharmacological actions are poorly understood. In this study, we employed a mouse middle cerebral artery occlusion (MCAO) and cellular oxygen and glucose deprivation (OGD) models to test the hypothesis that salidroside may restore mitochondrial quality control in neurons by modulating the relevant signaling. The results indicated that salidroside mitigated almost 40% the ischemia-induced brain infarct volumes in mice and the OGD-decreased viability of neurons to ameliorate the mitochondrial functions. Furthermore, salidroside treatment alleviated the OGD- or ischemia-induced imbalance of mitochondrial fission and fusion, mitophagy and promoted mitochondrial biogenesis in neurons by attenuating the AMPK activity. Moreover, salidroside alleviated 50% the OGD-promoted mitochondrial calcium fluorescence intensity and 5% mitochondria-associated membrane (MAM) area by down-regulating GRP75 expression independent of the AMPK signaling. Finally, similar findings were achieved in primary mouse neurons. Collectively, these data indicate that salidroside effectively restores the mitochondria dynamics, facilitates mitochondrial biogenesis by attenuating the AMPK signaling, and maintains calcium homeostasis in neurons independent of the AMPK activity.
红景天苷是 的一种活性成分，对脑缺血具有很强的保护作用。然而，其药理作用的机制尚不清楚。在这项研究中，我们采用小鼠大脑中动脉闭塞（MCAO）和细胞氧葡萄糖剥夺（OGD）模型来验证红景天苷可能通过调节相关信号通路来恢复神经元中线粒体质量控制的假说。结果表明，红景天苷可减轻约 40%的脑缺血诱导的小鼠脑梗死体积，并改善神经元的 OGD 降低的活力，从而改善线粒体功能。此外，红景天苷通过抑制 AMPK 活性减轻 OGD 或缺血诱导的线粒体分裂和融合、自噬以及促进神经元中线粒体生物发生的失衡。此外，红景天苷通过下调 GRP75 表达（不依赖于 AMPK 信号）减轻了 50%的 OGD 促进的线粒体钙荧光强度和 5%的线粒体相关膜（MAM）面积。最后，在原代小鼠神经元中也得到了类似的发现。总之，这些数据表明，红景天苷通过抑制 AMPK 信号通路有效地恢复线粒体动力学，促进线粒体生物发生，并维持神经元中的钙稳态，而不依赖于 AMPK 活性。
