目的 采用网络药理学方法探索冠心舒通胶囊治疗冠心病的“多成分-多靶点-多通路”网络调控机制。方法 基于液质联用技术从冠心舒通胶囊中辨识其化学物质组成,以口服生物利用度(OB)≥30%和类药性(DL)≥0.18筛选活性成分,进一步利用中药系统药理学数据库和分析平台(traditional Chinese medicine systems pharmacology,TCMSP)预测活性成分的作用靶点,并与通过文献挖掘及多种数据库搜寻的冠心病相关靶点进行比对,筛选冠心舒通胶囊治疗冠心病的关键靶点,最后借助于生物分子功能注释系统3.0(Molecule Annotation System 3.0, MAS 3.0)对得到的关键靶点进行通路注释分析。结果 基于液质联用技术辨识指认得到43个化合物;通过OB及DL筛选得到鞣花酸、隐丹参酮、丹参酮ⅡA等10个主要活性成分;这些成分可作用于CLP、LDLR、TNF等关键靶点26个,共涉及49条重要信号通路(P<0.05)。结论 冠心舒通胶囊可能主要通过对TGF-beta、T细胞受体、MAPK等信号通路的干预来发挥治疗冠心病的作用,体现了冠心舒通胶囊多成分、多靶点、多途径的作用特点,为进一步深入揭示冠心舒通胶囊治疗冠心病的作用机制奠定了一定基础。
Abstract
OBJECTIVE To explore the"multi-component, multi-target, multi-pathway" network regulation mechanism of Guanxinshutong caspules (GXST) in treatment of coronary heart disease by network pharmacology method. METHODS The chemical components of GXST were identified based on liquid chromatography-mass spectrometry (LC-MS), and the oral bioavailability (OB)≥30% and drug likeness (DL)≥0.18 were used as the screening conditions for obtaining active molecular compounds. The targets related to the active compounds were predicted through the Traditional Chinese Medicine Systems Pharmacology database (TCMSP).The relevant targets of coronary heart disease were searched through literature mining and multiple databases and compared with the predicted component targets. Finally, the targets were introduced into the Molecule Annotation System 3.0 (MAS 3.0)to analyze the main biological pathways. RESULTS Forty-three compounds were identified in GXST based on LC-MS technology and 10 main active compounds were determined through OB and DL screening, such as ellagic acid, cryptotanshinone, and tanshinone. These components affected 26 key targets, such as CLP, LDLR, TNF, et al, and 49 KEGG pathways were involved (P<0.05). CONCLUSION GXST produces therapeutic effect for coronary heart disease mainly through the TGF-beta, T cell receptors, and MAPK signaling pathway.This study further reveals the characteristics of the multi-component, multi-target and multi-pathway of GXST, and lays a certain foundation for further elucidation of the mechanism of GXST in the treatment of coronary heart disease.
关键词
冠心舒通胶囊 /
槲皮素 /
山柰酚 /
冠心病 /
靶点 /
信号通路
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Key words
Guanxinshutong capsule /
quercetin /
raempferol /
coronary heart disease /
target /
signaling pathway
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参考文献
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脚注
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基金
河南省重点研发与推广专项项目资助(182102310404);常州四药临床药学科研基金资助(CZSYJJ16030)
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