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生脉方改善秀丽隐杆线虫阿尔茨海默病模型的病理特征。

Shengmai Formula Ameliorates Pathological Characteristics in AD C. elegans.

作者信息

Zhang Weimin, Zhi Dejuan, Ren Hui, Wang Dong, Wang Xin, Zhang Zhanxin, Fei Dongqing, Zhu Hongmei, Li Hongyu

机构信息

Gansu High Throughput Screening and Creation Center for Health Products, School of Pharmacy, Lanzhou University, No. 199, Donggang West Road, Lanzhou, 730000, China.

Institute of Microbiology, School of Life Sciences, Lanzhou University, Lanzhou, China.

出版信息

Cell Mol Neurobiol. 2016 Nov;36(8):1291-1302. doi: 10.1007/s10571-015-0326-z. Epub 2016 Feb 17.

Abstract

Shengmai (SM) formula, a classical traditional Chinese medicine formula, is composed of Panax ginseng (Pg), Ophiopogon japonicus (Oj), and Schisandra Chinesis (Sc). SM has been clinically used to treat heart failure and ischemic heart disease. Although SM formula has been reported to be potential for fighting against Alzheimer's disease (AD) by previous works, there are many gaps in our knowledge on its usage in AD treatment on an organism level and will then need to be further clarified. In this study, transgenic Caenorhabditis elegans expressing human Aβ are used to evaluate SM formula efficacy to treat AD phenotype and to investigate its underlying mechanism. The results showed that SM formula ameliorated AD pathological characteristics of paralysis behavior and chemotaxis defect in transgenic C. elegans. With SM treatment, the number of Aβ deposits decreased, the levels of gene expressions of hsp16-2, hsp16-41, ace-1, ace-2, and TNFA1P1 homolog genes were down-regulated. Our results also showed that Oj exhibited more stronger effect on delaying paralysis in worms than Pg and Sc did, and synergistic action was observed between Pg and Oj, and Sc further enhanced the activity of Pg/Oj combination on delaying paralysis behavior. Further, SM with herbs of Pg, Oj, and Sc at a dose proportion of 9:9:6 exhibited superior therapeutic efficacy in comparison with herbs at other dose proportions. After SM formula extracted by ethanol, it delayed AD symptoms on a wider dose from 0.2 to 10.0 mg/mL with no toxic effect. These results provided more evidence for SM formula being potential to be used to treat AD.

摘要

生脉(SM)方是一种经典的中药方剂,由人参(Pg)、麦冬(Oj)和五味子(Sc)组成。SM已被临床用于治疗心力衰竭和缺血性心脏病。尽管先前的研究报道SM方在对抗阿尔茨海默病(AD)方面具有潜力,但在其在AD治疗中的机体水平应用方面,我们的认识仍存在许多空白,有待进一步阐明。在本研究中,利用表达人Aβ的转基因秀丽隐杆线虫来评估SM方治疗AD表型的疗效,并探究其潜在机制。结果表明,SM方改善了转基因秀丽隐杆线虫的AD病理特征,如麻痹行为和趋化缺陷。经SM处理后,Aβ沉积物数量减少,hsp16 - 2、hsp16 - 41、ace - 1、ace - 2和TNFA1P1同源基因的表达水平下调。我们的结果还表明,麦冬对延缓线虫麻痹的作用比人参和五味子更强,观察到人参和麦冬之间有协同作用,五味子进一步增强了人参/麦冬组合延缓麻痹行为的活性。此外,人参、麦冬和五味子按9:9:6剂量比例组成的SM方与其他剂量比例的药材相比,具有更优的治疗效果。乙醇提取的SM方在0.2至10.0 mg/mL的较宽剂量范围内均可延缓AD症状,且无毒性作用。这些结果为SM方具有治疗AD的潜力提供了更多证据。

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