基于网络药理学和分子对接技术探讨槲素治疗宫颈高危型人乳头瘤病毒的作用机制  

Exploring the Mechanisms of Action of Quercetin for the Treatment of Cervical High-Risk-Human Papilloma Virus Using Network Pharmacology and Molecular Docking

作　　者：王山云 洪慧斯 袁一鸣 尹因浩 曾建峰[1] 肖静[2] Shanyun Wang;Huisi Hong;Yiming Yuan;Yinhao Yin;Jianfeng Zeng;Jing Xiao(Department of Yuelai Clinic,Zhongshan Hospital of Traditional Chinese Medicine,Zhongshan,Guangdong,China;The Second Clinical School,Guangzhou University of Chinese Medicine,Guangzhou,Guangdong,China;Department of Science and Education,Zhongshan Hospital of Traditional Chinese Medicine,Zhongshan,Guangdong,China;Department of Clinical Pharmacy,Zhongshan Hospital of Traditional Chinese Medicine,Zhongshan,Guangdong,China;Department of Andrology,Zhongshan Hospital of Traditional Chinese Medicine,Zhongshan,Guangdong,China;Department of Gynecology,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou,Guangdong,China)

机构地区：[1]中山市中医院,广东中山528400 [2]广州中医药大学,广东广州510006

出　　处：《Chinese Medicine and Natural Products》2024年第1期35-41,I0028-I0032,共12页中医学报（英文）

基　　金：中山市科技局项目(220130114240704)。

摘　　要：目的:通过网络药理学和分子对接技术探讨槲皮素在治疗宫颈高危型人乳头瘤病毒(high—risk human papilloma virus,HR-HPV)中的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP,https://tcmsp—e.com/)获得槲皮素相关靶点,利用GeneCards数据库获得HR—HPV疾病靶点,通过Venny2.1.0获得槲皮素治疗HR-HPV的潜在治疗靶点,利用String数据库构建蛋白质相互作用(protein—protein interaction,PPI)网络,利用Cytoscape进行蛋白质相互作用网络的可视化和构建,利用R语言进行基因本体(geneontology,GO)富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes,KEGG)信号通路富集分析。使用AutoDock Vina软件进行分子对接。结果:从TCMSP数据库中鉴定出232个槲皮素相关靶点,从GeneCards中获得3421个疾病靶点。使用Veeny2.1.0软件获得139个潜在靶点。PPI分析显示,蛋白激酶B1(protein kinase B1,Akt1)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase1,MAPK1)、白细胞介素-6(interleukin-6,IL-6)、信号转导与转录激活因子3(signal transducer and activator of transcription 3,STAT3)和表皮生长因子受体(epidermal growth factor receptor,EGFR)可能是槲皮素治疗宫颈HR-HPV的中心靶点。GO和KEGG分析表明,槲皮素参与了多种功能途径、生物过程、分子类别和信号通路,包括Th17信号通路、肿瘤坏死因子(tumor necrosis factor,TNF)信号通路、EGFR信号通路、PI3K(磷脂酰肌醇-3激酶,phosphoinositide 3-kinase;PI3K)-Akt信号通路等。分子对接显示槲皮素与中心靶点结合良好。结论:槲皮素具有多方面的特性,靶向多种组分、途径和靶点,在治疗HR-HPV中主要通过调节炎症反应、氧化反应和凋亡过程进行干预。Objective Our objective was to investigate the therapeutic mechanism of quercetin in the management of cervical HR-HPV through the integration of network pharma-cology and molecular docking techniques.Methods The GeneCard database was utilized to analyze and identify potential therapeutic targets in HR-HPV.Subsequently,a protein–protein interaction(PPI)network was constructed by employing the String database.The visualization and construction of PPI networks were accomplished using Cytoscape.The R language was utilized to conduct Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses.Results A total of 154 active constituents of quercetin were identified through screening.Additionally,139 target genes associated with the effects of quercetin on cervical HR-HPV were predicted.PPI analyses revealed that threonine kinase Akt1,mitogen-activated protein kinase1,human IL-6 protein,signal transducer and activator of transcription 3,and epidermal growth factor receptor(EGFR)may serve as potential targets for quercetin in the treatment of cervical HR-HPV.Furthermore,GO and KEGG analyses demonstrated that quercetin is involved in various functional pathways,biological processes,molecular categories,including the Th17 signaling pathway,tumor necrotizing factor(TNF)signaling pathway,EGFR signaling pathway,PI3K-Akt signaling pathway,among others.Conclusion Quercetin exhibits multifaceted characteristics,targeting multiple com-ponents,pathways,and targets,in the therapeutic intervention of HR-HPV,primarily by modulating inflammatory responses,oxidation reactions,and apoptotic processes.

关 键 词：高危型人乳头瘤病毒 槲皮素 作用机制 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]