丹皮治疗新型冠状病毒肺炎的有效成分、核心靶点及作用机制  

Active ingredients,core targets and mechanism of mudan cortex in the treatment of COVID-19

作　　者：俞军 胡阳生 YU Jun;HU Yangsheng(Department of Pharmacy,The First Affiliated Hospital of Anhui Medical University,Hefei 230012,China;不详)

机构地区：[1]安徽医科大学第一附属医院药学部,合肥230012 [2]安徽省公共卫生临床中心

出　　处：《山东医药》2023年第23期19-23,共5页Shandong Medical Journal

基　　金：安徽省高校自然科学研究重点项目(KJ2021A0329);安徽医科大学校科研基金项目(2018xkj065、2022xkj057)。

摘　　要：目的基于网路药理学和分子对接技术探讨丹皮治疗新型冠状病毒肺炎(COVID-19)的有效成分、核心靶点及潜在作用机制。方法通过中药系统药理学分析平台(TCMSP)获取丹皮的有效成分及作用靶点,GeneCards®和OMIM®数据库获得COVID-19相关靶点,两者取交集后获得丹皮治疗COVID-19的潜在靶点。将潜在靶点输入STRING数据库,获取靶点蛋白在生物系统中的相互作用关系,建立蛋白互作网络(PPI)图筛选核心靶点,采用Cytoscape软件绘制COVID-19-丹皮—有效成分—靶点网络图,筛选丹皮主要活性成分。对潜在靶点进行GO和KEGG富集分析,获取潜在靶点的相关分子功能和信号通路。采用Discovery Studio 2019软件对靶点网络图中丹皮主要活性成分及临床常用于治疗COVID-19的药物奈玛特韦、瑞德西韦与COVID-19的药物治疗靶点3CL蛋白酶、血管紧张素转化酶2(ACE2)进行分子—蛋白对接。结果共获得丹皮有效成分6个,即槲皮素、丁子香萜、谷甾醇、山奈酚、(+)-儿茶素、单体5-{[5-(4-甲氧基苯基)-2-呋喃]亚甲基}巴比妥酸(简称巴比妥酸),有效成分作用靶点150个,与COVID-19相关靶点716个取交集后获得丹皮治疗COVID-19的潜在靶点36个。PPI图显示核心靶点主要包括血管内皮细胞生长因子受体(VEGFR)、白细胞介素6(IL-6)、IL-1B等。COVID-19-丹皮—有效成分—靶点网络图显示,丹皮治疗COVID-19的主要活性成分排名先后顺序为槲皮素、山奈酚、巴比妥酸和(+)-儿茶素,核心靶点为过氧化物酶体增殖物激活受体γ(PPARG)、环加氧酶2(PTGS2)、雌激素受体1(ESR1)。GO和KEGG富集分析得到61个分子功能和109个信号通路,分子功能主要包括细胞因子受体结合活性、DNA结合转录因子结合活性、信号受体激活因子活性等,信号通路主要包括脂质与动脉粥样硬化、IL-17、肿瘤坏死因子(TNF)家族等。分子—蛋白对接结果显示,与奈玛特韦、瑞德西韦相Objective To investigate the active ingredients,core targets,and potential mechanisms of mudan cor⁃tex in treatment of corona virus disease 2019(COVID-19)based on network pharmacology and molecular docking.Meth⁃ods The Traditional Chinese Medicine Systems Pharmacology(TCMSP)was used to obtain the main active ingredient compounds and targets of mudan cortex,and the GeneCards®and OMIM®databases were used to obtain COVID-19-related targets,and the potential targets of mudan cortex for COVID-19 treatment were obtained by intersecting the above two.The potential targets were input into the STRING database to obtain the interactions of the target proteins in the biological sys⁃tem and to build a PPI network,and the COVID-19-mudan cortex-active ingredient-target network was diagrammed using Cytoscape software.GO and KEGG enrichment analyses were performed on the potential targets to obtain the relevant gene functions and signaling pathways.The Discovery Studio 2019 software was used to perform molecule-protein docking of the main active components of mudan cortex in the target network diagram and the clinically used drugs Nematovir and Raltegravir in treatment of COVID-19 with the important targets of COVID-193CL protease and angiotensin-converting enzyme 2(ACE2).Results A total of 6 active ingredients of mudan cortex,quercetin,mairin,sitosterol,kaempferol,(+)-cat⁃echin,and 5-[[5-(4-methoxyphenyl)-2-furyl]methylene]barbituric acid and 150 their related targets were obtained,and 716 targets related to COVID-19 were intersected to obtain 36 potential targets of mudan cortex for the treatment of COVID-19.The PPI diagram showed that the core proteins were mainly VEGFA,IL-6,and IL-1B.The COVID-19-mudan cortex-active ingredient-target network diagram showed that the active ingredients of mudan cortex for COVID-19 were sequential⁃ly,quercetin,kaempferol,barbituric acid,and(+)-catechin,with the main targets of PPARG,PTGS2,and estrogen re⁃ceptor 1(ESR1).GO and KEGG enrichment analysis obtained 61 molecular function

关 键 词：丹皮 网络药理学 分子对接 槲皮素 血管内皮细胞生长因子受体 新型冠状病毒肺炎 

分 类 号：R969.4[医药卫生—药理学]