Center on Translational Neuroscience, College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China.
Department of Cell Biology & Medical Genetics, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen 518060, China.
Int J Med Sci. 2020 Aug 19;17(14):2207-2213. doi: 10.7150/ijms.47919. eCollection 2020.
2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) is the major active ingredient in 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.
2,3,5,4'-四羟基二苯乙烯-2-O-β-D-葡萄糖苷(THSG)是 的主要活性成分,具有多种健康益处,包括抗氧化、抗高血脂、抗癌、抗炎和神经保护。然而,目前尚不清楚 THSG 是否通过调节神经营养因子及其相关信号通路发挥神经保护功能。在本研究中,使用星形孢菌素(STS)处理海马神经元,建立神经损伤模型。我们发现 STS 诱导的细胞毒性导致明显的形态崩溃和起始细胞凋亡,同时 BDNF 和 TrkB/Akt 信号轴下调。相比之下,用 THSG 预处理的神经元对 STS 诱导的毒性具有抗性,并维持细胞存活。THSG 挽救了 STS 诱导的 BDNF 及其相关的 TrkB/Akt 信号功能障碍,并恢复了 Bcl-2 和 Caspase-3 的表达。然而,用 K252a 抑制 TrkB 活性或用 LY294002 抑制 Akt 信号通路会消除 THSG 的神经保护作用。因此,BDNF 和 TrkB/Akt 信号轴是 THSG 介导的神经保护功能的一个有希望的靶点。