Research Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
Translational Medicine Center, Honghui Hospital, Xi'an Jiaotong University, Xi'an, 710054, China.
Mol Cell Biochem. 2017 Dec;436(1-2):203-213. doi: 10.1007/s11010-017-3169-8. Epub 2017 Aug 29.
Our previous work demonstrated that tetrahydroxystilbene glucoside (TSG) was able to effectively attenuate 1-methyl-4-phenylpyridinium (MPP)-induced apoptosis in PC12 cells partially via inhibiting reactive oxygen species (ROS) generation. However, the precise molecular mechanisms of TSG responsible for suppressing neuronal apoptosis have not been fully elucidated. To investigate the possible mechanism, we studied the neuroprotective effects of TSG on MPP-induced PC12 cells apoptosis and explored the molecular mechanisms that mediated the effects of TSG. Our results showed that treatment with TSG prior to MPP exposure effectively attenuated the cell viability decrease in PC12 cells, reversed the cell apoptosis, and further restored the mitochondria membrane potential (MMP). In addition, TSG remarkably enhanced the anti-oxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and efficiently reduced the malondialdehyde (MDA) content in the PC12 cells. Meanwhile, TSG markedly upregulated the Bcl-2/Bax ratio, reversed release of Cytochrome c, and inhibited the activation of caspase-3 induced by MPP. Furthermore, TSG significantly inhibited the activation of p38 mitogen-activated protein kinase (p38MAPK) signaling pathway, while extracellular signal-regulated protein kinases (ERK) phosphorylation was not affected. Together, these findings provide the basis for TSG clinical application as a new therapeutic strategy in the treatment of neurodegenerative diseases.
我们之前的工作表明，二苯乙烯苷（TSG）能够通过抑制活性氧（ROS）的产生，有效减轻 1-甲基-4-苯基吡啶（MPP）诱导的 PC12 细胞凋亡。然而，TSG 抑制神经元凋亡的确切分子机制尚未完全阐明。为了研究可能的机制，我们研究了 TSG 对 MPP 诱导的 PC12 细胞凋亡的神经保护作用，并探讨了介导 TSG 作用的分子机制。我们的结果表明，在 MPP 暴露前用 TSG 处理可有效减轻 PC12 细胞活力下降，逆转细胞凋亡，并进一步恢复线粒体膜电位（MMP）。此外，TSG 显著增强了超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物酶（GSH-Px）的抗氧化酶活性，并有效降低了 PC12 细胞中的丙二醛（MDA）含量。同时，TSG 明显上调了 Bcl-2/Bax 比值，逆转了 Cytochrome c 的释放，并抑制了 MPP 诱导的 caspase-3 的激活。此外，TSG 显著抑制了 p38 丝裂原活化蛋白激酶（p38MAPK）信号通路的激活，而细胞外信号调节蛋白激酶（ERK）磷酸化不受影响。总之，这些发现为 TSG 作为治疗神经退行性疾病的新治疗策略的临床应用提供了依据。
