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补肾益智方治疗阿尔茨海默病的作用机制。

The Mechanisms of Bushen-Yizhi Formula as a Therapeutic Agent against Alzheimer's Disease.

机构信息

Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, 510405, China.

Department of Neurology & Psychology, Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, 518033, China.

出版信息

Sci Rep. 2018 Feb 15;8(1):3104. doi: 10.1038/s41598-018-21468-w.

DOI:10.1038/s41598-018-21468-w
PMID:29449587
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5814461/
Abstract

Bushen-Yizhi prescription (BSYZ) has been an effective traditional Chinese medicine (TCM) prescription in treating Alzheimer's disease (AD) for hundreds of years. However, the underlying mechanisms have not been fully elucidated yet. In this work, a systems pharmacology approach was developed to reveal the underlying molecular mechanisms of BSYZ in treating AD. First, we obtained 329 candidate compounds of BSYZ by in silico ADME/T filter analysis and 138 AD-related targets were predicted by our in-house WEGA algorithm via mapping predicted targets into AD-related proteins. In addition, we elucidated the mechanisms of BSYZ action on AD through multiple network analysis, including compound-target network analysis and target-function network analysis. Furthermore, several modules regulated by BSYZ were incorporated into AD-related pathways to uncover the therapeutic mechanisms of this prescription in AD treatment. Finally, further verification experiments also demonstrated the therapeutic effects of BSYZ on cognitive dysfunction in APP/PS1 mice, which was possibly via regulating amyloid-β metabolism and suppressing neuronal apoptosis. In conclusion, we provide an integrative systems pharmacology approach to illustrate the underlying therapeutic mechanisms of BSYZ formula action on AD.

摘要

补肾益智方（BSYZ）是一种治疗阿尔茨海默病（AD）的有效中药方剂，已有数百年的历史。然而，其作用机制尚未完全阐明。本研究采用系统药理学方法，揭示了 BSYZ 治疗 AD 的潜在分子机制。首先，我们通过计算机辅助药物设计（ADME/T）过滤分析获得了 329 种 BSYZ 的候选化合物，通过我们内部的 WEGA 算法将预测靶点映射到 AD 相关蛋白，预测了 138 个 AD 相关靶点。此外，我们通过多种网络分析，包括化合物-靶点网络分析和靶点-功能网络分析，阐明了 BSYZ 对 AD 的作用机制。进一步将 BSYZ 调节的几个模块整合到 AD 相关通路中，揭示了该方剂治疗 AD 的治疗机制。最后，进一步的验证实验也证明了 BSYZ 对 APP/PS1 小鼠认知功能障碍的治疗作用，可能是通过调节淀粉样蛋白-β代谢和抑制神经元凋亡。总之，我们提供了一种综合的系统药理学方法来阐明 BSYZ 方治疗 AD 的潜在治疗机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/a00074fbd902/41598_2018_21468_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/8d71afc1746d/41598_2018_21468_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/33b08aa49cb3/41598_2018_21468_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/6323979c2bcd/41598_2018_21468_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/92af91001f8a/41598_2018_21468_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/73539342669f/41598_2018_21468_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/e72e38589ed1/41598_2018_21468_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/4f4e3cb495fa/41598_2018_21468_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/c2ad9932e2e6/41598_2018_21468_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/a00074fbd902/41598_2018_21468_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/8d71afc1746d/41598_2018_21468_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/33b08aa49cb3/41598_2018_21468_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/6323979c2bcd/41598_2018_21468_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/92af91001f8a/41598_2018_21468_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/73539342669f/41598_2018_21468_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/e72e38589ed1/41598_2018_21468_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/4f4e3cb495fa/41598_2018_21468_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/c2ad9932e2e6/41598_2018_21468_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0033/5814461/a00074fbd902/41598_2018_21468_Fig9_HTML.jpg

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