Liu Jingjing, Wang Yanyan, Li Qinyuan, Liu Tao, Liu Xu, Zhang Han, Fu Zhifei, Dai Yifan, Yang Haiyuan, Wang Yu, Wang Ying
Department of Medical Genetics, School of Basic Medical Science, Nanjing Medical University, Nanjing 211166, China.
School of Medical Technology, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China.
Biomed Pharmacother. 2023 Nov;167:115507. doi: 10.1016/j.biopha.2023.115507. Epub 2023 Sep 16.
Phenylethanoid glycosides derived from Cistanche deserticola (PhGs) are plant-derived natural medicinal compounds that occur in many medicinal plants. This study aims to investigate whether PhGs treatment improves the stroke and its potential mechanisms. Adult male C57BL/6 J mice were administrated PhGs once daily for 7 days after MCAO surgery. The neurological score, and catwalk were evaluated on Day 1, 3 and 7 after ischemic stroke. Furthermore, triphenyl-2,3,5-tetrazoliumchloride (TTC) and hematoxylin-eosin (H&E) staining were used for evaluating the infarct volume and neuronal restoration. The effects of PhGs on NSCs proliferation were investigated in vitro and in vivo. Western blot was used to detect the proteins of Wnt/β-catenin signaling pathway. This study found that PhGs effectively improved the neurological functions in ischemic stroke mice. TTC and H&E staining demonstrated that PhGs not only reduced infarct volume, but also improved neuronal restoration. The immunohistochemistry and 5-Ethynyl-2-deoxyuridine (EdU) incorporation assays revealed that PhGs promoted the proliferation of neural stem cells (NSCs) in subventricular zone (SVZ). In addition, transcriptome analysis of NSCs showed that the Wnt/β-catenin signaling pathway was involved in the PhGs induced NSCs proliferation. Importantly, the related proteins in the Wnt/β-catenin signaling pathway were changed after PhGs treatment, including β-catenin, Wnt3a, GSK-3β, c-Myc. PhGs treatment improved the stroke through enhancing endogenous NSCs proliferation via activating Wnt/β-catenin signaling pathway. Due to its effect on the proliferation of NSCs, PhGs are a potential adjuvant therapeutic drug for post-stroke treatment.
来源于肉苁蓉的苯乙醇苷（PhGs）是存在于许多药用植物中的植物源天然药用化合物。本研究旨在探讨PhGs治疗是否能改善中风及其潜在机制。成年雄性C57BL/6 J小鼠在大脑中动脉闭塞（MCAO）手术后每天给药一次PhGs，持续7天。在缺血性中风后的第1、3和7天评估神经功能评分和步态分析。此外，使用氯化三苯基四氮唑（TTC）和苏木精-伊红（H&E）染色来评估梗死体积和神经元修复情况。在体外和体内研究了PhGs对神经干细胞（NSCs）增殖的影响。采用蛋白质免疫印迹法检测Wnt/β-连环蛋白信号通路的蛋白。本研究发现，PhGs能有效改善缺血性中风小鼠的神经功能。TTC和H&E染色表明，PhGs不仅减少了梗死体积，还改善了神经元修复。免疫组织化学和5-乙炔基-2'-脱氧尿苷（EdU）掺入试验显示，PhGs促进了脑室下区（SVZ）神经干细胞的增殖。此外，对NSCs的转录组分析表明，Wnt/β-连环蛋白信号通路参与了PhGs诱导的NSCs增殖。重要的是，PhGs处理后Wnt/β-连环蛋白信号通路中的相关蛋白发生了变化，包括β-连环蛋白、Wnt3a、糖原合成酶激酶-3β（GSK-3β）、原癌基因c-Myc。PhGs治疗通过激活Wnt/β-连环蛋白信号通路增强内源性NSCs增殖来改善中风。由于其对NSCs增殖的作用，PhGs是一种潜在的中风后辅助治疗药物。
