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Potential molecular mechanisms mediating the protective effects of tetrahydroxystilbene glucoside on MPP+-induced PC12 cell apoptosis

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Abstract

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.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No. 81371411 and 81173590).

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Authors and Affiliations

  1. Research Center of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Lingling Zhang, Xin Sun, Leitao Wu, Tao Li & Jianzong Chen

  2. Translational Medicine Center, Honghui Hospital, Xi’an Jiaotong University, Xi’an, 710054, China

    Lingling Zhang, Cuicui Liu & Hao Yang

  3. Clinical Pharmacy, Honghui Hospital, Xi’an Jiaotong University, Xi’an, 710054, China

    Linhong Huang

  4. Department of Interventional Radiology, Tangdu Hospital, Fourth Military Medical University, Xi’an, 710038, China

    Xiaobing Li

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  1. Lingling Zhang
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Correspondence to Hao Yang or Jianzong Chen.

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Zhang, L., Huang, L., Li, X. et al. Potential molecular mechanisms mediating the protective effects of tetrahydroxystilbene glucoside on MPP+-induced PC12 cell apoptosis. Mol Cell Biochem 436, 203–213 (2017). https://doi.org/10.1007/s11010-017-3169-8

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  • DOI: https://doi.org/10.1007/s11010-017-3169-8

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