广西师范大学学报（自然科学版） ›› 2021, Vol. 39 ›› Issue (5): 198-209.doi: 10.16088/j.issn.1001-6600.2020082201

• 研究论文 • 上一篇    下一篇

十大功劳甘草汤治疗肝炎的网络药理学研究

蒋向辉1*, 谭荣1, 杨永平2, 肖清淙1   

  1. 1.凯里学院 大健康学院,贵州 凯里 556011;
    2.贵州奥特药业有限公司,贵州 凯里 556011
  • 收稿日期:2020-08-22 修回日期:2020-11-02 出版日期:2021-09-25 发布日期:2021-10-19
  • 通讯作者: 蒋向辉(1974—),男,湖南安化人,凯里学院教授,博士。E-mail:jxfei789@163.com
  • 基金资助:
    贵州省科学技术基金(黔科合J字[2015]2131);贵州省科技厅社会发展项目(黔科合支撑[2018]2823)

Analysis of Network Pharmacology and Confirmation of Mahonia fortunei (Lindl. ) Fedde and Glycyrrhiza uralensis Fisch Decoction for Hepatitis

JIANG Xianghui1*, TAN Rong1, YANG Yongping2, XIAO Qingzong1   

  1. 1. College of Health, Kaili University, Kaili Guizhou 556011, China;
    2. Guizhou Oute Pharmaceutical Co. Ltd., Kaili Guizhou 556011, China
  • Received:2020-08-22 Revised:2020-11-02 Online:2021-09-25 Published:2021-10-19

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摘要： 为了探讨十大功劳甘草汤治疗肝炎的潜在作用机制,借助中药系统药理学数据库TCMSP(traditional Chinese medicine systems pharmacology)对十大功劳和甘草的生物活性成分和潜在作用靶点进行预测,通过Cytoscape 3.6.1软件构建十大功劳甘草汤活性成分-靶点-疾病网络,利用OMIM(online mendelian inheritance in man)和GeneCards 数据库进行肝炎疾病作用相关靶点的筛选,通过PPI(protein-protein interaction network)分析数据库构造十大功劳甘草汤和肝炎交集蛋白的相互作用网络,通过Omicshare平台对核心靶点进行GO(gene ontology)分析,并对核心靶点进行KEGG(kyoto encyclopedia of genes and genomes)代谢通路分析。在对十大功劳甘草汤主要活性成分与作用靶点进行分子对接分析的基础上,通过十大功劳甘草水提物治疗乙酰氨基酚(APAP)诱导的急性肝损伤小鼠,测定血清中相关生化指标,探讨其活性成分的作用机制。结果表明:十大功劳甘草汤治疗肝炎的交集靶点蛋白有25个,其中核心靶点有12个;筛选出山柰酚、柚皮素和异鼠李素3种潜在的先导化合物及其作用蛋白前列腺素过氧化物合酶(PTGS);十大功劳甘草水提物、山柰酚、柚皮素和异鼠李素可显著降低肝损伤小鼠血清中丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)、嘌呤核苷磷酸化酶(PNP)和丙二醛(MDA)的含量,提高谷胱甘肽(GSH)和超氧化物岐化酶(SOD)含量;十大功劳甘草汤中的活性成分可能通过参与炎症因子氧化应激的调节而对抗肝损伤。

关键词: 网络药理学, 十大功劳, 甘草, 肝炎, 分子确证

Abstract: To explore the potential mechanism of Mahonia fortunei (Lindl.)Fedde and Glycyrrhiza uralensis Fisch decoction for hepatitis based on network pharmacology. TCMSP and TCMID databases are used to collect active ingredients and targets of Mahonia fortunei (Lindl.) Fedde and Glycyrrhiza uralensis Fisch decoction, GeneCards and OMIM databases are used to screen for genes related to hepatitis and to intersect with the target genes of active ingredients in Perilla frutescens and Bidens pilosa L. decoction, a protein mutual network (PPI network) was built by the string website, and the biological process of the intersection target was analyzed by the Reactome database and the KEGG metabolic pathway analysis on the Omicshare platform. A component-target-channel network was built by Cytoscape software, screened core targets and core pathways by conducting network topology analysis method, the core target protein crystal structure was further imported into Autodock software to confirm the molecular docking of the active ingredient and the core target protein. By measuring the biochemical indicators in the acute liver injury model, the mechanism of Mahonia fortunei (Lindl.) Fedde and Glycyrrhiza uralensis Fisch decoction for hepatitis were studied. The result showed that Mahonia fortunei (Lindl.) Fedde and Glycyrrhiza uralensis Fisch decoction contains 95 ingredients, including 872 potential targets. There are 198 targets related to hepatitis in Genecards and OMIM databases. 25 intersection targets were obtained by intersection analysis, and 12 core targets were further obtained from the drug-compound-target network graph. By molecular docking confirmation analysis, three potential lead compounds including Kaempferol, naringenin, and isorhamnetin were screened, and the potential target proteins were confirmed. The experimental results showed that the water extract of Mahonia fortunei (Lindl.) Fedde and Glycyrrhiza uralensis Fisch, kaempferol, naringenin and isorhamnetin can significantly reduce the content of ALT, AST, PNP and MDA in the serum of mice, and increase the content of GSH and SOD. The active ingredients in Mahonia fortunei (Lindl.) Fedde and Glycyrrhiza uralensis Fisch decoction may avoid liver injury by regulation of oxidative stress.

Key words: network pharmacology, Mahonia fortunei (Lindl.)Fedde, Glycyrrhiza uralensis Fisch, hepatitis, molecular confirmation

中图分类号: 

  • R285
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