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Systems Pharmacology Dissection of Mechanisms of Dengzhan Xixin Injection against Cardiovascular Diseases.
Chemical & Pharmaceutical Bulletin ( IF 1.5 ) Pub Date : 2020-09-01 , DOI: 10.1248/cpb.c20-00122
Panpan Wang 1, 2 , Hui Huang 2 , Bing Chen 2 , Ya Su 2 , Peiying Shi 1 , Hong Yao 2
Affiliation  

Dengzhan Xixin injection (DZXXI), a herbal product prepared from a Chinese herb called Erigeron breviscapus, is a classical and traditional therapeutic for cadiovascular diseases (CVDs), including coronary heart disease (CHD), angina, and stroke, etc. However, its potential pharmacology mechanism against CVDs remains unclear. In this paper, a systems pharmacology-based strategy is presented for predicting drug targets and understanding therapeutic mechanisms of DZXXI against CVDs. The main ingredients were identified by HPLC-diode array detector (DAD). The target fishing was performed on the PharmMapper Server (http://lilab-ecust.cn/pharmmapper/). Potential targets were confirmed by two molecular docking tools, Sybyl-X 1.3 and Ledock to ensure the accuracy. The resulting target proteins were applied as baits to fish their related diseases and pathways from the molecular annotation system (MAS 3.0, http://bioinfo.capitalbio.com/mas3/) and Kyoto Encyclopedia of Genes and Genomes (KEGG) database (http://www.genome.jp/kegg/). Network generation and topological analysis were performed in Cytoscape 3.6.0. 15 main ingredients from DZXXI were identified. Forty five putative drug targets and 50 KEGG pathways, which have highly relevance to the therapeutic effects of DZXXI against CVDs, were then obtained. The systems analysis suggested that DZXXI could attenuate cardiac fibrosis, regulate cardiac contractility, and preserve heart function in adverse cardiac remodeling; meanwhile DZXXI also could have the function of activating blood circulation and dilating blood vessels. DZXXI exerts its therapeutic effects on CVDs possibly through multi-targets including CMA1, epidermal growth factor receptor (EGFR), phenylalanine-4-hydroxylase (PAH), SRC, F7, etc., and multi-pathways including Focal adhesion, mitogen-activated protein kinase (MAPK) signaling pathway, complement and coagulation cascades, Wnt signaling pathway, vascular endothelial growth factor (VEGF) signaling pathway, Renin-angiotensin system, etc.

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中文翻译:

灯盏细辛注射液抗心血管疾病机理的系统药理学研究。

灯盏细辛注射液(DZXXI)是一种由草药制成的草药产品,称为灯盏花Erigeron breviscapus),是心血管疾病(CVD)的经典和传统疗法,包括冠心病(CHD),心绞痛和中风等。。但是,其针对CVD的潜在药理学机制仍不清楚。在本文中,提出了一种基于系统药理学的策略来预测药物靶标并了解DZXXI对CVD的治疗机制。主要成分通过HPLC-二极管阵列检测器(DAD)鉴定。目标钓鱼是在PharmMapper服务器(http://lilab-ecust.cn/pharmmapper/)上执行的。潜在的目标已通过两种分子对接工具Sybyl-X 1.3和Ledock确认以确保准确性。从分子注释系统(MAS 3.0,http://bioinfo.capitalbio.com/mas3/)和《京都基因与基因组百科全书》(KEGG)数据库(http: ://www.genome.jp/kegg/)。网络生成和拓扑分析是在Cytoscape 3.6.0中进行的。确定了DZXXI的15种主要成分。然后获得了45个推定的药物靶标和50条KEGG通路,这些通路与DZXXI对CVD的治疗效果高度相关。系统分析表明,DZXXI可以减轻心脏纤维化,调节心脏收缩力,并在不良心脏重塑中保留心脏功能。同时DZXXI还具有激活血液循环和扩张血管的功能。DZXXI可能通过包括CMA1,表皮生长因子受体(EGFR),苯丙氨酸-4-羟化酶(PAH),SRC,F7,然后获得了与DZXXI对CVD的治疗作用高度相关的药物。系统分析表明,DZXXI可以减轻心脏纤维化,调节心脏收缩力,并在不良心脏重塑中保留心脏功能。同时DZXXI还具有激活血液循环和扩张血管的功能。DZXXI可能通过包括CMA1,表皮生长因子受体(EGFR),苯丙氨酸-4-羟化酶(PAH),SRC,F7,然后获得了与DZXXI对CVD的治疗作用高度相关的药物。系统分析表明,DZXXI可以减轻心脏纤维化,调节心脏收缩力,并在不良心脏重塑中保留心脏功能。同时DZXXI还具有激活血液循环和扩张血管的功能。DZXXI可能通过包括CMA1,表皮生长因子受体(EGFR),苯丙氨酸-4-羟化酶(PAH),SRC,F7,同时DZXXI还具有激活血液循环和扩张血管的功能。DZXXI可能通过包括CMA1,表皮生长因子受体(EGFR),苯丙氨酸-4-羟化酶(PAH),SRC,F7,同时DZXXI还具有激活血液循环和扩张血管的功能。DZXXI可能通过包括CMA1,表皮生长因子受体(EGFR),苯丙氨酸-4-羟化酶(PAH),SRC,F7,,以及多种途径,包括粘着斑,丝裂原活化蛋白激酶(MAPK)信号传导途径,补体和凝血级联,Wnt信号传导途径,血管内皮生长因子(VEGF)信号传导途径,肾素-血管紧张素系统等。

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更新日期:2020-09-12
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