Cardiovascular Disease Chemogenomics Knowledgebase-guided Target Identification and Drug Synergy Mechanism Study of an Herbal Formula.
Cardiovascular Disease Chemogenomics Knowledgebase-guided Target Identification and Drug Synergy Mechanism Study of an Herbal Formula.
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心血管疾病化学基因组学知识库引导的中药方靶点识别及药物协同机制研究
DOI：
10.1038/srep33963
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发表时间：
2016-09-28
影响因子：
4.6
通讯作者：
Xie XQ
中科院分区：
文献类型：
--
作者：
Zhang H;Ma S;Feng Z;Wang D;Li C;Cao Y;Chen X;Liu A;Zhu Z;Zhang J;Zhang G;Chai Y;Wang L;Xie XQ
联合治疗是临床上治疗多种疾病的常用方法。在众多成功的案例中，中药方剂在治疗上具有协同作用，在毒性上具有拮抗作用。然而，由于高实验费用和多组分草药的复杂性，表征药物组合的潜在分子协同作用仍然是一项具有挑战性的任务。为了了解联合治疗的基本原理，我们研究了由三种药物组成的着名中药四逆汤作为模型。本研究应用我们建立的疾病特异性化学基因组学数据库和系统药理学方法TargetHunter，探讨四逆汤治疗心血管疾病的协同作用机制。(1)我们构建了一个心血管疾病特异性化学基因组学数据库，包括药物、靶蛋白、化学物质和相关通路。(2)利用我们实现的化学信息学工具，我们绘制了四逆汤有效成分与其靶点之间的相互作用网络。(3)我们还通过计算机预测和实验证实，这些成分的组合可以减轻副作用。总的来说，我们的研究结果表明，我们的心血管疾病特异性数据库成功地应用于复杂的草药配方的系统药理学分析，预测分子协同机制，并导致更好地理解组合治疗。
Combination therapy is a popular treatment for various diseases in the clinic. Among the successful cases, Traditional Chinese Medicinal (TCM) formulae can achieve synergistic effects in therapeutics and antagonistic effects in toxicity. However, characterizing the underlying molecular synergisms for the combination of drugs remains a challenging task due to high experimental expenses and complication of multicomponent herbal medicines. To understand the rationale of combination therapy, we investigated Sini Decoction, a well-known TCM consisting of three herbs, as a model. We applied our established diseases-specific chemogenomics databases and our systems pharmacology approach TargetHunter to explore synergistic mechanisms of Sini Decoction in the treatment of cardiovascular diseases. (1) We constructed a cardiovascular diseases-specific chemogenomics database, including drugs, target proteins, chemicals, and associated pathways. (2) Using our implemented chemoinformatics tools, we mapped out the interaction networks between active ingredients of Sini Decoction and their targets. (3) We alsoin silicopredicted and experimentally confirmed that the side effects can be alleviated by the combination of the components. Overall, our results demonstrated that our cardiovascular disease-specific database was successfully applied for systems pharmacology analysis of a complicated herbal formula in predicting molecular synergetic mechanisms, and led to better understanding of a combinational therapy.
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影响因子：
5.4
作者：
Luo, Jianxing;Zhang, Yang;Zhu, Hong
通讯作者：
Zhu, Hong
治疗性增强和进步的草药结合：理论，实践和未来观点。
DOI：
10.3390/molecules18055125
发表时间：
2013-05-03
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Che CT;Wang ZJ;Chow MS;Lam CW
通讯作者：
Lam CW
影响因子：
8.6
作者：
Bienfait B;Ertl P
通讯作者：
Ertl P
影响因子：
5.6
作者：
Feng Z;Pearce LV;Xu X;Yang X;Yang P;Blumberg PM;Xie XQ
通讯作者：
Xie XQ
影响因子：
82.9
作者：
Hevener, AL;He, WM;Olefsky, J
通讯作者：
Olefsky, J