Liu Bowen, Zhang Qian, Ke Chienchih, Xia Zhenyan, Luo Cheng, Li Yang, Guan Xiaowei, Cao Xiang, Xu Yun, Zhao Yonghua
Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Biotherapy, Shenzhen Luohu People's Hospital, Shenzhen, China.
Front Neurosci. 2019 May 29;13:515. doi: 10.3389/fnins.2019.00515. eCollection 2019.
The traditional Chinese medicine Ginseng-Angelica-Shanseng-Pulvis (GASP) has been used to treat stroke for 300 years. This present study investigated if it can induce increases in neurogenesis following cerebral ischemic injury.
Rats following middle cerebral artery occlusion were orally treated with high, medium, and low doses of a standardized GASP extract.
After 14 days, treatment with GASP improved regional blood flow and infarction volume by magnetic resonance imaging scanning, enhanced Ki67 expression in the subventricular zone, increased brain-derived neurotrophic factor (BDNF) secretion, Nestin, and bone morphogenetic protein (BMP) 2/4 expressions in the hippocampus in a dose-dependent manner. Interestingly, low-dose treatment with GASP downregulated doublecortin and Notch1 expressions in the hippocampus, as well as upregulated glial fibrillary acidic protein expression in the subgranular zone and hairy and enhancer of split (Hes) 5 expression in the hippocampus, while treatment with middle and high doses of GASP reversed these results. Meanwhile, the consumed time was shortened in the basket test and the adhesive removal test and the spending time on exploring novel objects was prolonged by GASP treatment whose effects were more obvious at day 14 post-ischemia.
Our study demonstrates that treatment with GASP increases neurogenesis and ameliorates sensorimotor functions and recognition memory. We hypothesize that these effects are thought be mediated by an effect on the BMP2/4 pathway and Notch1/Hes5 signal. Due to its beneficial efficacy, GASP can be recognized as an alternative therapeutic agent for ischemic stroke.
中药参芪归芎散已用于治疗中风300年。本研究调查其是否能在脑缺血损伤后诱导神经发生增加。
大脑中动脉闭塞后的大鼠口服高、中、低剂量的标准化参芪归芎散提取物。
14天后,通过磁共振成像扫描,参芪归芎散治疗改善了局部脑血流量和梗死体积,增强了脑室下区的Ki67表达,增加了海马中脑源性神经营养因子(BDNF)的分泌、巢蛋白和骨形态发生蛋白(BMP)2/4的表达,且呈剂量依赖性。有趣的是,参芪归芎散低剂量治疗下调了海马中双皮质素和Notch1的表达,上调了颗粒下区胶质纤维酸性蛋白的表达以及海马中毛状分裂增强子(Hes)5的表达,而中、高剂量参芪归芎散治疗则逆转了这些结果。同时,参芪归芎散治疗缩短了网篮试验和黏附去除试验中的耗时,并延长了探索新物体的时间,其效果在缺血后第14天更为明显。
我们的研究表明,参芪归芎散治疗可增加神经发生,改善感觉运动功能和认知记忆。我们推测这些作用可能是通过对BMP2/4通路和Notch1/Hes5信号的影响介导的。由于其有益疗效,参芪归芎散可被视为缺血性中风的替代治疗药物。