基于网络药理学的西红花治疗动脉粥样硬化作用机制探讨

doi:10.12092/j.issn.1009-2501.2020.06.007

摘要/Abstract

摘要： 目的: 基于网络药理学方法探究西红花对治疗动脉粥样硬化的潜在作用靶点。方法: 运用中药系统药理学数据库和分析平台(TCMSP)筛选西红花有效成分的作用靶点;运用GeneCards、OMIM数据库筛选动脉粥样硬化的药物靶点构建疾病靶点网络,进而构建药物-成分-疾病-靶点的网络图并进行蛋白质网络互作、GO功能分析、KEGG通路等分析。运用AutoDock对有效成分和关键靶点进行分子对接。结果: 选择生物利用度(OB)＞30%,且类药性(DL)＞0.18作为西红花中的有效成分筛选条件,共得到5个主要成分和272个靶点;通过对药物-成分-疾病-靶点的网络图进行分析,得到多化合物共同作用靶点26个,单化合物作用靶点50个;通过蛋白质网络互作分析对蛋白质靶点基因进行筛选(degree>50),共筛选出19个相关靶点基因;GO分析共包含99条富集结果,KEGG数据库中共包含116条通路对动脉粥样硬化有治疗作用。西红花的5个主要成分均可与Fluid shear stress and atherosclerosis重要信号通路中的关键蛋白VCAM-1和eNOS进行对接,其中异鼠李素与VCAM-1、山萘酚与eNOS的结合能更低。结论: 通过网络药理学分析发现西红花治疗动脉粥样硬化的有效成分及潜在作用靶点,预测西红花治疗动脉粥样硬化的主要作用机制,为其活性成分的研究提供了理论依据。

关键词: 西红花, 动脉粥样硬化, 网络药理学, 作用机制

Abstract: AIM: To investigate the active components and potential mechanism of saffron (Crocus sativus L.) in inhibiting atherosclerotic lesion by using network pharmacological method. METHODS: TCMSP database was used to systematically analyze the active components of saffron. At the same time, GeneCards and OMIM databases were used to analyze the genes and proteins according to atherosclerosis mechanism. A follow-up analysis was establishing drug-compound-disease-target network. The potential targets were analyzed for protein interactions, and gene enrichment analysis was carried out by GO and KEGG. Molecular docking was carried out between characteristic ingredients of saffron and its key targets. RESULTS: A total of 5 effective components and 272 genes were screened in saffron used oral bioavailability (OB)>30% and drug likeness (DL)>0.18 as the screening conditions. 26 targets of multiple compounds acting together and 50 targets of a single compound were screened from drug-compound-disease-target network. 19 targets, 99 enrichment results and 116 pathways were screened by protein interactions, GO and KEGG gene enrichment analysis respectively. Molecular docking results showed that all 5 active components could be bind with spontaneously VCAM-1 or eNOS, which are representative proteins of fluid shear stress and atherosclerosis pathway. Isorhamnetin had the lowest binding energy with VCAM-1, and kaempferol had the lowest binding energy with eNOS. CONCLUSION: The results preliminarily verified the main activity components and pharmacology mechanism in saffron and provided a good foundation for further study on the antiatherosclerotic mechanism of saffron.

Key words: saffron, atherosclerosis, network pharmacology, mechanism

中图分类号:

李梦颖, 司明东, 温子帅, 石欢, 李新蕊, 张园园, 王红芳, 马东来, 楚立. 基于网络药理学的西红花治疗动脉粥样硬化作用机制探讨[J]. 中国临床药理学与治疗学, 2020, 25(6): 649-657.

LI Mengying, SI Mingdong, WEN Zishuai, SHI Huan, LI Xinrui, ZHANG Yuanyuan, WANG Hongfang, MA Donglai, CHU Li. Mechanism of saffron in treating atherosclerosis based on network pharmacology method[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2020, 25(6): 649-657.

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