摘要
该研究利用网络药理学方法探索通塞脉片治疗动脉粥样硬化的药效物质和分子作用机制。经分子对接、分子-靶蛋白网络分析发现,通塞脉片中有97个分子可与动脉粥样硬化相关靶蛋白产生较好的相互作用(对接得分大于等于7),其中37个分子可作用于2个以上靶点,且具有较高的介数,推测这37个分子可能是通塞脉片治疗动脉粥样硬化的主要活性成分群。同时,所预测活性成分中含有较多的黄酮类和皂苷类化合物,提示该2类成分应在药效物质基础和质量标准研究中重点关注。靶点网络特征分析显示,通塞脉片主要活性成分可通过与Toll样受体(TLR1,TLR2)、基质金属蛋白酶(MMP1,MMP2,MMP3,MMP9)、血管紧张素转化酶(ACE)、白三烯A4水解酶(LTA4-H)、5-脂氧酶(5-LOX)、过氧化物酶体增殖物激活受体(PPARα,PPARγ)等22个主要靶蛋白作用,起到调节炎症、增加斑块稳定性、保护内皮细胞、参与血脂调节及抗凝等作用,从而参与对动脉粥样硬化病理过程不同环节的调控,最终实现对动脉粥样硬化的治疗。该研究揭示了通塞脉片治疗动脉粥样硬化的主要药效物质及其可能的分子作用机制,印证了通塞脉片多成分、多靶点、整体调节的作用特点,为后续系统进行通塞脉片药效物质基础和作用机制实验研究提供了理论依据。
Network pharmacology method was adopted in this study to explore the active compounds and mechanism of Tongsaimai tablets for atherosclerosis. In molecular docking and molecular-target protein network analysis,97 molecules in Tongsaimai tablets showed good interaction with the atherosclerosis-related target protein（ docking score≥7）,and 37 molecules of them could act on more than 2 targets（ ≥2） with higher betweenness,suggesting that these 37 molecules might be the main active compounds group in Tongsaimai tablets for atherosclerosis treatment. Furthermore,the predicted active compounds contained more flavonoids and saponins,reminding more attention should be paid on flavonoids and saponins in study of effective compounds and quality standards of Tongsaimai tablets. Targets network analysis showed that,the active compounds of Tongsaimai tablets could regulate inflammation,stabilize plaque,protect vascular endothelial cell,regulate blood lipid and inhibit blood coagulation through acting on the main 22 target proteins,such as Toll-like receptors（ TLR1,TLR2）,matrix metalloproteinase（ MMP1,MMP2,MMP3,MMP9）,angiotensin converting enzyme（ ACE）,leukotriene A4 hydrolase（ LTA4-H）,5-lipoxidase（ 5-LOX）,peroxisome proliferators-activated receptors（ PPARα,PPARγ）. These active compounds can participate in regulating different pathologic stages of atherosclerosis and thus treat atherosclerosis finally. This study revealed the main active compounds and possible mechanism of Tongsaimai tablets for treatment of atherosclerosis and meanwhile,verified the characteristics of multi-components,multi-targets and integral regulation for Tongsaimai tablets,providing theoretical references for the following systematic laboratory experiments on effective compounds and action mechanism of Tongsaimai Tablet.
出处
《中国中药杂志》
CAS
CSCD
北大核心
2016年第9期1706-1712,共7页
China Journal of Chinese Materia Medica
基金
国家"重大新药创制"科技重大专项(2013ZX09402203)
关键词
中药
通塞脉片
网络药理学
分子对接
动脉粥样硬化
traditional Chinese medicine
Tongsaimai tablet
network pharmacology
molecular docking
atherosclerosis
