国际知名衰老期刊《Aging》近日发表了名为“ Bacopaside I 通过免疫调节的清除作用改善APP/PS1小鼠的认知损伤“的文章，该研究由第二军医大学药学院张卫东教授课题组完成 (Bacopaside I ameliorates cognitive impairment in APP/PS1 mice via immune ‐mediated clearance of β‐amyloid )。

目前 阿尔茨海默症（AD）是世界范围内最常见的神经退行性疾病之一。该疾病的发病机理极为复杂，与多个蛋白有关。Ab片段是AD疾病过程中具有神经毒性的主要成分。目前临床使用的治疗AD药物都不能从根本上起到治疗的作用，而且一旦停止用药疾病就会复发，可用的药物匮乏。发现新的作用机理且副作用小的药物迫在眉睫。

从中草药中发现活性成分是一条非常有效的途径，并且取得了巨大的成功，如抗疟药青蒿素的发现。传统草药假马齿苋能提高记忆力和智力，它在印度阿育吠陀传统医学体系被用作神经补剂已有将近3000年的历史。假马齿苋的标准提取物长期给药研究已被证明具有抗脑缺血、抗精神抑郁症、抗精神分裂症、抗焦虑和抗AD的作用，但是有效成分不清，作用机制不明。

张卫东教授课题组长期致力于基于中药的新药发现。课题组前期研究发现假马齿苋皂苷Bacopaside I（BS-I）具有很好的保护神经细胞、治疗脑缺血和抑郁症的作用。本项研究进一步发现BS-I能显著减少APP/PS1转基因小鼠b淀粉样蛋白斑块负荷、改善其学习能力和长期空间记忆障碍。综合利用基因组学和蛋白质组学技术，发现BS-I通过调节先天免疫和吞噬作用，促进淀粉样蛋白的减少，是一种新型的作用机制。该研究成果对开发具有免疫调节作用的天然活性成分，为新的AD治疗药物的开发提供了新的研究途径。（来源：第二军医大学）

Bacopaside I ameliorates cognitive impairment in APP/PS1 mice via immune-mediated clearance of β-amyloid

Abstract  Standardized extracts of Bacopa monniera (BME) have been shown to exert a neuroprotective effect against mental diseases, such as depression, anxiety and Alzheimer's disease (AD), in chronic administration studies. However, its mechanism of action has remained unclear. In this study, we evaluated the therapeutic effect of Bacopaside I (BS-I), a major triterpenoid saponin of BME, on the cognitive impairment and neuropathology in APP/PS1 transgenic mice and explored the possible mechanism from a biological systems perspective. We found that BS-I treatment significantly ameliorated learning deficits, improved long-term spatial memory, and reduced plaque load in APP/PS1 mice. We constructed BS-I's therapeutic effect network by mapping the nodes onto the protein-protein interaction (PPI) network constructed according to their functional categories based on genomic and proteomic data. Because many of the top enrichment categories related to the processes of the immune system and phagocytosis were detected, we proposed that BS-I promotes amyloid clearance via the induction of a suitable degree of innate immune stimulation and phagocytosis. Our research may help to clarify the neuroprotective effect of BME and indicated that natural saponins target the immune system, which may offer new research avenues to discover novel treatments for AD.

原文链接：http://www.impactaging.com/papers/v8/n3/pdf/100913.pdf