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基于分子网络建模的三种经典冠心病中药方剂的比较药物基因组学分析。

A comparative pharmacogenomic analysis of three classic TCM prescriptions for coronary heart disease based on molecular network modeling.

机构信息

Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, China.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.

出版信息

Acta Pharmacol Sin. 2020 Jun;41(6):735-744. doi: 10.1038/s41401-019-0352-3. Epub 2020 Feb 12.

Abstract

Traditional Chinese medicine (TCM) has evolved over several thousands of years, which has been shown to be efficacious in the treatment of ischemic heart disease. Three classical TCM prescriptions, namely Xuefu Zhuyu Decoction, Zhishi Xiebai Guizhi Decoction, and Gualou Xiebai Banxia Decoction, have been extensively used in the treatment of coronary heart disease (CHD). Based on molecular network modeling, we performed a comparative pharmacogenomic analysis to systematically determine the drug-targeting spectrum of the three prescriptions at molecular level. Wide-area target molecules of CHD were covered, which was a common feature of the three decoctions, demonstrating their therapeutic functions. Meanwhile, collective signaling involved metabolic/pro-metabolic pathways, driving and transferring pathways, neuropsychiatric pathways, and exocrine or endocrine pathways. These organized pharmacological disturbance was mainly focused on almost all stages of CHD intervention, such as anti-atherosclerosis, lipid metabolism, inflammation, vascular wall function, foam cells formation, platelets aggregation, thrombosis, arrhythmia, and ischemia-reperfusion injury. In addition, heterogeneity analysis of the global pharmacological molecular spectrum revealed that signaling crosstalk, cascade convergence, and key targets were tendentious among the three decoctions. After all, it is unadvisable to rank the findings on targeting advantages of the three decoctions. Comparative pharmacological evidence may provide an appropriate decoction scheme for individualized intervention of CHD.

摘要

中医(TCM)经过几千年的发展,已被证明在治疗缺血性心脏病方面是有效的。三种经典的中药方剂,即血府逐瘀汤、栀子泻白桂枝汤和瓜蒌薤白半夏汤,已广泛用于治疗冠心病(CHD)。基于分子网络建模,我们进行了比较药物基因组学分析,以系统地确定这三种方剂在分子水平上的药物靶向谱。广泛覆盖了 CHD 的靶点分子,这是这三种方剂的共同特征,表明了它们的治疗功能。同时,集体信号涉及代谢/前代谢途径、驱动和转移途径、神经精神途径以及外分泌或内分泌途径。这些有组织的药理干扰主要集中在 CHD 干预的几乎所有阶段,如抗动脉粥样硬化、脂质代谢、炎症、血管壁功能、泡沫细胞形成、血小板聚集、血栓形成、心律失常和缺血再灌注损伤。此外,全球药理分子谱的异质性分析表明,三种方剂之间存在信号转导交叉、级联收敛和关键靶点的趋势。总之,不建议对这三种方剂的靶向优势进行排名。比较药理证据可能为 CHD 的个体化干预提供适当的方剂方案。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fbb2/7656848/717d8ef61008/41401_2019_352_Fig1_HTML.jpg

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