天然产物研究与开发 ›› 2023, Vol. 35 ›› Issue (9): 1602-1612.doi: 10.16333/j.1001-6880.2023.9.014

• 数据研究 • 上一篇    下一篇

基于网络药理学与分子对接探究黄芩有效成分对酒精性肝病的作用机制及效果验证

叶敬榕1,刘   瑞2,程   成3,张凤英3,杨   雪3*   

  1. 1承德医学院中药研究所 河北省中药研究与开发重点实验室,承德 067000;2云南中医药大学第一附属医院,昆明 650021;3承德医学院基础医学院,承德 067000
  • 出版日期:2023-09-22 发布日期:2023-09-21
  • 基金资助:
    河北省高等学校科学技术研究青年拔尖人才计划(BJK2023035);河北省科技厅项目(2020);河北省医学科学研究计划(20220406)

Mechanism of active ingredients from Scutellaria Radix on alcoholic liver disease based on network pharmacology and molecular docking and effect verification

YE Jing-rong1,LIU Rui2,CHENG Cheng3,ZHANG Feng-ying3,YANG Xue3*#br# #br#
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  1. 1Hebei Province Key Lab.of Research and Development for Chinese Medicine,Chinese Medicine Research Institute,Chengde Medical University,Chengde 067000,China;2The First Affiliated Hospital of Yunnan University of Traditional Chinese Medicine Kunming,Yunnan 650021,China;3 Basic Medical Sciences,Chengde Medical University 067000,China
  • Online:2023-09-22 Published:2023-09-21

摘要:

通过网络药理学和分子对接技术探究中药黄芩治疗酒精性肝病的作用机制,并通过体外细胞实验验证黄芩有效成分对酒精性肝病的治疗效果。在TCMSP、Swiss ADME和Swiss Target Prediction数据库中检索获得黄芩有效成分及其作用靶点;在GeneCards、OMIM、DisGeNET、TTD和PharmGKB数据库中检索获得酒精性肝病相关的疾病靶点;利用String数据库构建靶点相互作用网络;通过Metascape数据库对关键靶点进行京都基因与基因组百科全书(KEGG)通路富集分析、基因本体(GO)富集分析。采用Cytoscape 3.8.0软件构建黄芩治疗酒精性肝病的“有效成分-靶点-通路”互作网络,并筛选出黄芩有效成分和关键靶点进行分子对接。基于网络药理学和分子对接结果,采用体外细胞实验初步验证预测结果。将黄芩有效成分进行ADME筛选后共获得27个,且这27个有效成分可以通过257个基因靶点对酒精性肝病起到治疗作用,其中关键核心靶点有SRC、AKT1、PIK3R1、STAT3、PIK3CA等。KEGG信号通路富集分析结果显示,黄芩治疗酒精性肝病的主要信号通路包括癌症的途径、PI3K-Akt信号通路、脂质与动脉粥样硬化、化学致癌-活性氧物种、前列腺癌等;分子对接结果提示山姜素或将是黄芩治疗酒精性肝病的关键有效成分之一;体外细胞实验证实山姜素可显著改善大鼠肝细胞BRL 3A的酒精性损伤状态。通过网络药理学、分子对接技术和细胞实验的结果可以分析并推断中药黄芩可通过多成分、多靶点的方式对酒精性肝病起到预防和治疗的作用。其中山姜素作为关键有效成分之一,可为进一步利用黄芩开发治疗酒精性肝损伤相关药物提供依据及参考。

关键词: 网络药理学, 分子对接, 细胞实验, 黄芩, 酒精性肝病, 作用机制

Abstract:

Network pharmacology and molecular docking technology were adopted to explore the possible mechanism of Scutellaria Radix in the treatment of alcoholic liver disease.The therapeutic effect of active ingredient of Scutellaria Radix on alcoholic liver disease was verified by cell experiment in vitro.The effective components and targets of Scutellaria Radix were retrieved from TCMSP,Swiss ADME and Swiss Target Prediction databases;The disease targets related to alcoholic liver disease were retrieved from GeneCards,OMIM,DisGeNET,TTD and PharmGKB databases;Using String database to build target interaction network;Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene ontology (GO) enrichment analysis were conducted for key targets through metascape database.The "active ingredient target pathway" interaction network of Scutellaria Radix for the treatment of alcoholic liver disease was constructed by using Cytoscape 3.8.0 software,and the active ingredient and key target of Scutellaria Radix were screened for molecular docking.Based on the results of network pharmacology and molecular docking,the prediction results were preliminarily verified by cell experiments in vitro.A total of 27 active components of Scutellaria Radix were obtained after ADME screening,and these 27 active components could play a therapeutic role in alcoholic liver disease through 257 gene targets,among which the key core targets are SRC,AKT1,PIK3R1,STAT3,PIK3CA,etc.The enrichment analysis of KEGG signal pathway showed that the main signal pathways of Scutellaria Radix in treating alcoholic liver disease included cancer pathway,PI3K Akt signal pathway,lipid and atherosclerosis,chemical carcinogenic reactive oxygen species,prostate cancer,etc;Molecular docking results suggest that Alpinetin may be one of the key effective ingredients of Scutellaria Radix in the treatment of alcoholic liver disease;In vitro cell experiments proved that Alpinetin could significantly improve the alcoholic injury of rat liver cells BRL3A.Through the results of network pharmacology,molecular docking technology and cell experiment,it can be analyzed and inferred that Scutellaria Radix can play a role in the prevention and treatment of alcoholic liver disease through multi-component and multi target methods.As a key active ingredient,Alpinetin can provide basis and reference for further development of drugs related to the treatment of alcoholic liver injury by using Scutellaria Radix.

Key words: network pharmacology, molecular docking, cell experiment, Scutellaria Radix, alcoholic liver disease, action mechanism

中图分类号:  R285