Int J Med Sci 2020; 17(14):2207-2213. doi:10.7150/ijms.47919

Research Paper

2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside eliminates staurosporine-induced cytotoxicity by restoring BDNF-TrkB/Akt signaling axis

Teng-Teng Ren1*, Sheng-Rui Fan1*, Xiu-Yuan Lang1, Yun Yu1, Rongfeng Lan2✉, Xiao-Yan Qin1✉

1. Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China.
2. Department of Cell Biology & Medical Genetics, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen 518060, China.
*These authors contributed equally as first authors.

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Citation:
Ren TT, Fan SR, Lang XY, Yu Y, Lan R, Qin XY. 2,3,5,4'-tetrahydoxystilbene-2-O-β-D-glucoside eliminates staurosporine-induced cytotoxicity by restoring BDNF-TrkB/Akt signaling axis. Int J Med Sci 2020; 17(14):2207-2213. doi:10.7150/ijms.47919. Available from https://www.medsci.org/v17p2207.htm

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Abstract

2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) is the major active ingredient in Plygonum multiflorum that displays a great deal of health-benefits including anti-oxidation, anti-hyperlipidemia, anti-cancer, anti-inflammation and neuroprotection. However, it is unclear whether THSG exerts neuroprotective functions by regulating neurotrophic factors and their associated signaling pathways. In this study, hippocampal neurons were challenged with staurosporine (STS) to establish a neural damage model. We found that STS-induced cytotoxicity introduced significant morphological collapse and initiating cell apoptosis, along with the down regulation of BDNF and TrkB/Akt signaling axis. In contrast, neurons pretreated with THSG showed resistance to STS-induced toxicity and maintained cell survival. THSG rescued STS induced dysfunctions of BDNF and its associated TrkB/Akt signaling, and restored the expression of Bcl-2 and Caspase-3. However, inhibition of TrkB activity by K252a or Akt signaling by LY294002 abolished the neuroprotective effects of THSG. Therefore, BDNF and TrkB/Akt signaling axis is a promise target for THSG mediated neuroprotective functions.

Keywords: Akt, BDNF, K252a, LY294002, staurosporine, THSG, TrkB