基于网络药理学与分子对接技术探究加味泽泻汤治疗梅尼埃病的作用机制  

Mechanism of Modified Zexie Decoction in the Treatment of Meniere′s Disease Based on Network Pharmacology and Molecular Docking Technology

作　　者：赵赫[1] 董云芳[1] 何玉瑶 刘晓庆 侯晓莹 胡文文 钟利群[1] ZHAO He;DONG Yunfang;HE Yuyao;LIU Xiaoqing;HOU Xiaoying;HU Wenwen;ZHONG Liqun(Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院,北京100700

出　　处：《中西医结合心脑血管病杂志》2023年第6期1019-1029,共11页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：北京中医药大学东直门医院2020年度科技创新专项(No.DZMKJCX-2020-017)。

摘　　要：目的:探讨加味泽泻汤治疗梅尼埃病的潜在作用机制。方法:从TCMSP、TCMID、BATMAN-TCM平台中收集加味泽泻汤组方中药物的活性成分及靶点,经标准化处理后利用Cytoscape软件绘制加味泽泻汤活性成分-靶点网络图并分析其核心成分;从GeneCards、OMIM、DisGeNET及CTD疾病数据库中收集梅尼埃病相关的疾病靶点,从而得到药物-疾病共有靶点,筛选出加味泽泻汤治疗梅尼埃病的潜在作用靶点并绘制药物活性成分-疾病靶点网络图;筛选提取加味泽泻汤和梅尼埃病的交集网络制作药物-疾病互作网络,通过计算相关属性值得到核心靶点,利用Metascape数据库对核心靶点进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析,并可视化。最后使用分子对接技术对加味泽泻汤核心活性成分与核心靶点对接并进行可视化处理。结果:经过筛选共得到加味泽泻汤药物活性成分39个,相关靶点144个;梅尼埃病疾病相关靶点1556个,其中,有药物-疾病共同靶点44个,通过富集分析及筛选,得到排名靠前的GO功能条目及KEGG信号通路。分子对接得到4个关键化合物和3个核心靶点,具有较好的结合性,验证了网络药理学预测结果。结论:加味泽泻汤治疗梅尼埃病可能通过其关键成分β-谷甾醇、柚皮素、薯蓣皂苷元、川陈皮素、黄芩素、豆甾醇和卡维丁作用于前列腺素内过氧化物合酶2(PTGS2)、热休克蛋白90AA1(HSP90AA1)、肾上腺素能受体β2(ADRB2)3个核心靶点蛋白,通过调节炎症反应、氧化应激反应及环磷腺苷(cAMP)通路等发挥作用。Objective:To explore the potential mechanism of Modified Zexie Decoction in the treatment of Meniere′s disease.Method:The active ingredients and targets of the drugs in the prescriptions of Modified Zexie Decoction from TCMSP,TCMID,and BATMAN-TCM platforms were collected.Disease targets related to Meniere′s disease were collected from GenecCards,OMIM,DisGeNET,and CTD disease databases.Thus,the common drug-disease targets were obtained,the potential targets of Modified Zexie Decoction in the treatment of Meniere′s disease were screened,and the active ingredient-disease target network diagram was drawn.The intersection network of Modified Zexie Decoction and Meniere′s disease was screened and extracted to construct the drug-disease interaction network.The core targets were obtained by calculating the relevant attribute values,and the gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway of the core targets were analyzed and visualized using the Metascape database.Finally,molecular docking technology was used to dock the core active ingredients of Modified Zexie Decoction with the core target and perform visualization processing.Result:After screening,a total of 39 active ingredients of Modified Zexie Decoction and 144 related targets were obtained,1556 related targets for Meniere′s disease,including 44 common drug-disease targets.Through enrichment analysis and screening,the top-ranked GO functional items and KEGG signaling pathway were included.Molecular docking yielded 4 key compounds and 3 core targets,which showed better binding and verified the prediction results of network pharmacology.Conclusion:Modified Zexie Decoction in the treatment of Meniere′s disease may act by its key components including Beta-sitosterol,naringenin,diosgenin,nobiletin,baicalein,stigmasterol,and cavidine.These components may act on the three cores of prostaglandin endoperoxide synthase 2(PTGS2),Heat shock protein 90AA1(HSP90AA1),and adrenergic receptor beta 2(ADRB2).The target protein plays a r

关 键 词：梅尼埃病 网络药理学 分子对接技术 加味泽泻汤 

分 类 号：R285[医药卫生—中药学]