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基于系统药理学的方法发现中药方剂六味五灵用于肝衰竭的新治疗用途。

A systems pharmacology-oriented discovery of a new therapeutic use of the TCM formula Liuweiwuling for liver failure.

机构信息

China Military Institute of Chinese Medicine, 302 Military Hospital, Beijing, PR China.

Traditional Chinese Medicine College, Beijing University of Traditional Chinese Medicine, Beijing, PR China.

出版信息

Sci Rep. 2018 Apr 4;8(1):5645. doi: 10.1038/s41598-018-21515-6.

DOI:10.1038/s41598-018-21515-6
PMID:29618826
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5884779/
Abstract

Multiple components of traditional Chinese medicine (TCM) formulae determine their treatment targets for multiple diseases as opposed to a particular disease. However, discovering the unexplored therapeutic potential of a TCM formula remains challenging and costly. Inspired by the drug repositioning methodology, we propose an integrated strategy to feasibly identify new therapeutic uses for a formula composed of six herbs, Liuweiwuling. First, we developed a comprehensive systems approach to enrich drug compound-liver disease networks to analyse the major predicted diseases of Liuweiwuling and discover its potential effect on liver failure. The underlying mechanisms were subsequently predicted to mainly attribute to a blockade of hepatocyte apoptosis via a synergistic combination of multiple effects. Next, a classical pharmacology experiment was designed to validate the effects of Liuweiwuling on different models of fulminant liver failure induced by D-galactosamine/lipopolysaccharide (GalN/LPS) or thioacetamide (TAA). The results indicated that pretreatment with Liuweiwuling restored liver function and reduced lethality induced by GalN/LPS or TAA in a dose-dependent manner, which was partially attributable to the abrogation of hepatocyte apoptosis by multiple synergistic effects. In summary, the integrated strategy discussed in this paper may provide a new approach for the more efficient discovery of new therapeutic uses for TCM formulae.

摘要

多种中药（TCM）配方成分决定了它们治疗多种疾病而不是特定疾病的靶点。然而，发现中药配方未被探索的治疗潜力仍然具有挑战性和成本高昂。受药物重定位方法的启发，我们提出了一种综合策略，以合理地确定由六种草药组成的配方——六味五灵的新治疗用途。首先，我们开发了一种全面的系统方法来丰富药物化合物-肝脏疾病网络，以分析六味五灵的主要预测疾病，并发现其对肝衰竭的潜在影响。随后预测其潜在机制主要归因于通过多种作用的协同组合来阻止肝细胞凋亡。接下来，设计了一个经典的药理学实验来验证六味五灵对 D-半乳糖胺/脂多糖（GalN/LPS）或硫代乙酰胺（TAA）诱导的不同暴发性肝衰竭模型的作用。结果表明，六味五灵预处理以剂量依赖的方式恢复了 GalN/LPS 或 TAA 诱导的肝损伤和降低死亡率，这部分归因于多种协同作用阻断了肝细胞凋亡。总之，本文讨论的综合策略可能为更有效地发现中药配方的新用途提供一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/08b063c19ce1/41598_2018_21515_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/036dc145fd00/41598_2018_21515_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/75b48df4ed4a/41598_2018_21515_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/b4097de0a59c/41598_2018_21515_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/b4382d063253/41598_2018_21515_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/4b37ec44df10/41598_2018_21515_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/8fb2f5ae854f/41598_2018_21515_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/08b063c19ce1/41598_2018_21515_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/036dc145fd00/41598_2018_21515_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/75b48df4ed4a/41598_2018_21515_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/b4097de0a59c/41598_2018_21515_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/b4382d063253/41598_2018_21515_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/4b37ec44df10/41598_2018_21515_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/8fb2f5ae854f/41598_2018_21515_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd26/5884779/08b063c19ce1/41598_2018_21515_Fig7_HTML.jpg

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