黄芪桂枝五物汤治疗强直性脊柱炎的网络药理学探讨

doi:10.6040/j.issn.1671-7554.0.2021.0656

摘要/Abstract

摘要： 目的运用网络药理学和分子对接技术,探讨黄芪桂枝五物汤治疗强直性脊柱炎(AS)的分子机制。方法按照黄芪桂枝五物汤的组成,在TCMSP 数据库上搜索其化学成分和作用靶点,并对药物靶点进行基因注释;分别从Gene Cards、OMIM、PharmGkb、TTD和DrugBank五个数据库中搜索AS疾病相关靶点。然后利用Cytoscape 3.8.0软件将药物、活性化学成分、药物与疾病交集靶点三者构建“中药-活性有效成分-交集靶点”可视化网络;将可视化网络数据导入String数据库,构建蛋白互作网络;利用R语言软件和R包对结果进行GO和KEGG富集分析;最后对核心有效成分和核心靶点进行分子对接。结果共获取黄芪桂枝五物汤活性化合物74个,根据疾病-中药汤剂共有的靶标逆向筛选中药汤剂活性成分后,剩余32个,预测出对应靶点997个;AS疾病相关靶点2 234个,交集靶点78个;利用CytoNCA插件二次打分后,共筛选得到8个核心靶点。GO富集分析共获得1 990条结果,KEGG富集分析共获得135个结果;分子对接结果表明,核心有效成分与核心基因的靶点能够稳定对接。结论黄芪桂枝五物汤治疗AS是通过槲皮素、芍药苷、山奈酚等多种成分作用于PTGS2、IL6、TNF、VEGFA、IL1B、ICAM1、STAT1、CXCL8等多个基因靶点,从而影响“脂质和动脉粥样硬化”“AGE-RAGE信号通路”“IL-17信号通路”“TNF信号通路”“NF-kappa B信号通路”等多条相关通路发挥作用。

关键词: 强直性脊柱炎, 黄芪桂枝五物汤, 和血通痹, 网络药理学, 分子对接

Abstract: Objective To investigate the molecular mechanism of Huangqi Guizhi Wuwutang in the treatment of ankylosing spondylitis(AS)by using network pharmacology and molecular docking technology. Methods The chemical components and targets of Huangqi Guizhi Wuwutang were searched in TCMSP database, and gene annotation of drug targets were carried out. AS disease-related targets were searched from Gene Cards, OMIM, PharmGkb, TTD, and DrugBank database. Then, a visual network of “traditional Chinese medicine-components-intersection target” was constructed by using Cytoscape 3.8.0 software among drugs, active chemical components and intersection target. The visual network result data were imported into the String database to construct the protein interaction network. R language software and R package were used to analyze GO and KEGG enrichment. Finally, molecular docking was conducted between the core active component and the core target. Results A total of 74 active compounds of Huangqi Guizhi Wuwutang were obtained. After the reverse screening of active ingredients of TCM decoction according to the common targets of diseases and TCM decoction, 32 active ingredients were reserved, and 997 corresponding targets were predicted. A total of 2,234 AS related targets and 78 genes were intersected. Eight core targets were selected after the second scoring using CytoNCA plug-in R software. A total of 1,990 and 135 enrichment terms were acquired by GO and KEGG enrichment analyses, respectively. The results of molecular docking showed that the target of the active component and the target of the core gene could be docked stably. Conclusion In the treatment of AS, Huangqi Guizhi Wuwutang acts on PTGS2, IL6, TNF, VEGFA, IL1B, ICAM1, STAT1, CXCL8 and other gene targets through quercetin, paeoniflorin, kaempferol and other components. Thus, it can affect the function of “lipid and atherosclerosis” “AGE-RAGE signaling pathway” “IL-17 signaling pathway” “TNF signaling pathway” “NF-kappa B signaling pathway” and other related pathways.

Key words: Ankylosing spondylitis, Huangqi Guizhi Wuwutang, Blood paralysis, Network pharmacology, Molecular docking

中图分类号:

R681.5

李明波,黄燕波,刘俊城,任东成,谭成双,徐继禧,丁金勇. 黄芪桂枝五物汤治疗强直性脊柱炎的网络药理学探讨[J]. 山东大学学报 (医学版), 2022, 60(3): 29-38.

LI Mingbo, HUANG Yanbo, LIU Juncheng, REN Dongcheng, TAN Chengshuang, XU Jixi, DING Jinyong. Exploration of Huangqi Guizhi Wuwutang in the treatment of ankylosing spondylitis based on network pharmacology[J]. Journal of Shandong University (Health Sciences), 2022, 60(3): 29-38.

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