目的：借助网络药理学手段探究复方双花片治疗流行性腮腺炎的主要活性成分和作用机制。 方法：在中药系统药理学数据库和分析平台以及GeneCards数据库分别获取复方双花片的化学成分及作用靶点和流行性腮腺炎的靶点后获得共同靶点。采用STRING软件构建共同靶点蛋白互作图后进行基因本体论功能富集分析和京都基因与基因组百科全书通路富集分析，并构建“药物-成分-靶点-通路”网络图，拓扑分析获得主要活性成分与关键靶点，进行分子对接。结果：获得活性成分包括槲皮素、毛地黄黄酮、山奈酚等11个黄酮类，荷包牡丹碱、清风藤碱、去氧喜树碱3个生物碱，β-谷甾醇和豆甾醇2个植物甾醇，牛蒡子苷、异落叶松脂素等4个木脂素类。关键靶点前列腺素内过氧化物合酶 2(Prostaglandin-endoperoxide Synthase 2，PTGS2)、热休克蛋白90AB1(Heat Shock Protein 90 k Da Alpha，Class B member 1，HSP90AB1)、肿瘤坏死因子(Tumor Necrosis Factor，TNF)等11个。主要富集在T细胞受体信号通路、Toll样受体信号通路、NF-κB信号通路等分子信号通路，主要涉及促进 RNA聚合酶Ⅱ启动子转录、炎症反应及调节NO生物合成等生物过程。分子对接表明活性成分与关键靶点有一定的作用力。结论：复方双花片中的槲皮素、山奈酚、β-谷甾醇等成分可能通过PTGS2、 HSP90AB1、TNF等靶点和T细胞受体信号通路、Toll样受体信号通路等阻止病毒复制，降低炎性反应和提高机体免疫力而发挥治疗流行性腮腺炎的作用。
Abstract
Objective: To investigate the main activate ingredients and mechanism of compound Shuanghua tablet in the treatment of mumps by network pharmacology. Methods: The common targets were obtained followed by the chemical ingredients and targets in compound Shuanghua tablet, and the targets of the mumps were analyzed using TCMSP and GeneCards database, respectively. After the interaction map of common targets proteins was established by STRING software, Gene Ontology functional enrichment analysis and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes were conducted, the "drugcomponent-target-pathway" network diagram was constructed. The major activate ingredients and crucial target were obtained by topology analysis, and molecular docking was conducted. Results: The active components included 11 flavonoids (quercetin, digitalone and kaempferol, etc.), 3 alkaloids (paeonine, cephalotenine and deoxycamptothecine), 2 phytosterols (β–sitosterol, stigmasterol), and 4 lignans (arctiin, isolaruolin, etc.), PTGS2, HSP90AB1 and TNF, as the key protein targets.Mainly enriched in T cell receptor signaling pathway, Toll-like receptor signaling pathway, NF-κB signaling pathway and other molecular signaling pathways, mainly involved in promoting RNA polymerase Ⅱ promoter transcription, infl ammatory response and regulating NO biosynthesis and other biological processes.Molecular docking shows a certain interaction between active ingredients and key targets. Conclusion: Quercetin, kamanol and β-sitosterol in compound Shuanghua tablet might play important roles in the treatment of mumps by suppressing virus replication, reducing infl ammatory response and improving immunity through PTGS2, HSP90AB1 and TNF and other targets, T cell receptor signaling pathway and Tolllike receptor signaling pathway.
关键词
网络药理学；复方双花片；流行性腮腺炎；活性成分；机制
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Key words
network pharmacology； compound Shuanghua tablet； mumps； active ingredients； mechanism
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脚注
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基金
国家自然科学基金青年科学基金项目(编号 82000284)；陕西省自然科学基金(编号 2020JQ-609)；中国博士后科学基金(编号 2020M683701XB)；西安交通大学口腔医院青年科研基金项目(编号 201704)
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