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基于网络药理和实验验证探究中药通过健脾作用治疗白细胞减少症的作用机制

Mechanism of Traditional Chinese Medicine strengthening the spleen in treating leukopenia based on network pharmacology and experimental analyses
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摘要 目的运用数据挖掘、网络药理学和实验验证探讨中药通过健脾作用治疗白细胞减少症的用药规律、药效物质基础及潜在的作用机制。方法在中国知网、万方数据知识服务平台、维普网和PubMed数据库中检索健脾中药复方治疗白细胞减少症的临床文献,运用古今医案云平台在线分析软件和SPSS Modeler 18统计分析软件寻找核心药物组;利用中药系统药理学数据库和分析平台(TCMSP)、GeneCards数据库、OMIM数据库检索、Cytoscape 3.7.2软件、STRING数据库获取关键基因和主要有效成分,利用Metascape进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析;采用MTT法检测细胞增殖率,采用qPCR法检测关键基因mRNA水平表达。结果共筛选得到90篇有效文献,共计91首中药复方,党参-当归-黄芪为核心药物组合。肿瘤坏死因子(TNF)、白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)、JUN为核心靶点,槲皮素、木犀草素、山奈酚、芒柄花素、豆甾醇为主要有效成分,其主要作用机制可能通过癌症的途径、TNF信号通路、p53信号通路等来实现。健脾中药黄芪、党参、当归提取物和有效成分芒柄花素、槲皮素对人单核细胞白血病细胞(THP-1)具有促进增殖作用,芒柄花素对化疗诱导的THP-1细胞生长具有促进增殖的作用,芒柄花素能够抑制炎症细胞因子IL-6、IL-1β、TNF-α和刺激抗炎因子IL-10、原癌基因JUN的分泌。结论初步揭示黄芪等多种中药通过多成分、多靶点发挥健脾作用,参与抗肿瘤、抗炎、免疫调节等相关信号通路,治疗白细胞减少症。 Objective To explore the potential mechanisms of Traditional Chinese Medicine strengthening the spleen in treating leukopenia using the data mining,network pharmacology and then confirmed by the in vitro experiments.Methods The clinical literature in TCM spleen strengthening compound treatment of leukopenia was searched in the online databases of CNKI,WANFANG,CQVIP and PubMed.The Ancient and Modern Medical Records Cloud Platform and IBM SPSS modeler 18.0 were used to identify the core drugs in these prescribed compounds,while the effective ingredients vs.the core genes were assessed using the systematic pharmacology analytic platform of Chinese Medicine(TCMSP),GeneCards database,OMIM database,Cytoscape 3.7.2 software,and STRING database.Next,the gene ontology(GO)terms and the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were used to identify the gene functions and signaling.After that,human peripheral blood mononuclear cells(THP-1)were cultured in vitro and assessed for cell viability using the MTT assay and gene expression using RT-qPCR.Results A total of 90 papers with 91 prescriptions were identified and Dangshen-Danggui-Huangqi were the core drug combination.Quercetin,Luteolin,Kaempferol,Formononetin,and Stigmasterol were the effective ingredients,while the tumor necrosis factor(TNF),interleukin-6(IL-6),IL-1β,IL-10,and JUN were the core genes for action of these compounds.Furthermore,the potential mechanism of spleen strengthening TCM treatment of leukopenia could involve in regulation of the pathway of cancer,TNF signal pathway and p53signaling pathway.Dangshen,Danggui,Huangqi,Formononetin,and Quercetin could promote THP-1 cell viability in vitro.Formononetin was able to inhibit expression of IL-6 and IL-1β,TNF-αm RNA,but induce IL-10 and JUN mRNA.Conclusion Many TCM herbs,like Huangqi,treatment of leukopenia for spleen strengthening were through regulation of multi targets,such as the anti-tumor,anti-inflammatory,and immunity,and other related signal pathways.
作者 毛幼儿 陈梦艳 王珏 刘曦 高建莉 MAO You-er;CHEN Meng-yan;WANG Jue;LIU Xi;GAO Jian-li(Department of Pharmacy,Ningbo Municipal Hospital of Traditional Chinese Medicine,Zhejiang Chinese Medical University,Ningbo,Zhejiang 315010,China;School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou,Zhejiang 310053,China;Hangzhou TCM Hospital of Zhejiang Chinese Medical University,Hangzhou,Zhejiang 310007,China;Department of Traditional Chinese Medicine,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou,Zhejiang 325003,China)
出处 《浙江中西医结合杂志》 2023年第3期216-224,共9页 Zhejiang Journal of Integrated Traditional Chinese and Western Medicine
基金 国家自然科学基金青年项目(No.81904197) 第四轮宁波市中医医学重点扶植学科(No.2022-ZF02)。
关键词 中药 健脾 白细胞减少症 数据挖掘 网络药理学 实验验证 Traditional Chinese Medicine Spleen strengthening Leukopenia Data mining Network pharmacology In vitro experiment
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