The Mechanisms of Bushen-Yizhi Formula as a Therapeutic Agent against Alzheimer's Disease.
The Mechanisms of Bushen-Yizhi Formula as a Therapeutic Agent against Alzheimer's Disease.
复制标题
补肾益智方治疗阿尔茨海默病的机制。
DOI：
10.1038/s41598-018-21468-w
复制
发表时间：
2018-02-15
影响因子：
4.6
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Cai H;Luo Y;Yan X;Ding P;Huang Y;Fang S;Zhang R;Chen Y;Guo Z;Fang J;Wang Q;Xu J
补肾益智方是数百年来治疗阿尔茨海默病的有效中药方剂。然而，其潜在的机制尚未完全阐明。本研究从系统药理学的角度揭示BSYZ治疗AD的分子机制。首先，我们通过计算机ADME/T筛选分析获得了329个BSYZ候选化合物，并通过我们的内部WEGA算法将预测的靶点映射到AD相关蛋白，预测了138个AD相关靶点。此外，我们还通过多网络分析，包括复合靶点网络分析和目标函数网络分析，阐明了BSYZ对AD的作用机制。此外，由BSYZ调控的几个模块被整合到AD相关通路中，以揭示该方剂治疗AD的治疗机制。最后，进一步的验证实验也证实了补肾益智方对APP/PS1小鼠认知功能障碍的治疗作用，其机制可能是通过调节淀粉样蛋白β代谢和抑制神经细胞凋亡来实现的。综上所述，我们提供了一种综合系统药理学的方法来阐明补肾益智方治疗AD的潜在机制。
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.
登录
查看更多内容
DOI：
10.3233/jad-160907
发表时间：
2017
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Hane FT;Robinson M;Lee BY;Bai O;Leonenko Z;Albert MS
通讯作者：
Albert MS
影响因子：
5.4
作者：
Hou XQ;Yan R;Yang C;Zhang L;Su RY;Liu SJ;Zhang SJ;He WQ;Fang SH;Cheng SY;Su ZR;Chen YB;Wang Q
通讯作者：
Wang Q
AlzhCPI：预测阿尔茨海默病的化学-蛋白质相互作用的知识库
影响因子：
3.7
作者：
Fang J;Wang L;Li Y;Lian W;Pang X;Wang H;Yuan D;Wang Q;Liu AL;Du GH
通讯作者：
Du GH
影响因子：
2.6
作者：
Cai, Hao-Bin;Wu, Guang-Liang;Wang, Qi
通讯作者：
Wang, Qi
DOI：
10.1021/ci0003101
发表时间：
2001-03-01
期刊：
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
影响因子：
--
作者：
He, M;Yan, XJ;Xie, GR
通讯作者：
Xie, GR