目的 采用网络药理学方法探讨白灵片治疗白癜风的作用机制。方法 利用中药系统药理数据库与分析平台(TCMSP)及UniProt数据库平台,对白灵片主要成分的有效活性化合物和有效靶点基因进行检索、收集和筛选。通过DisGeNET、OMIM和 GeneCards 数据库查询白癜风的相关致病基因并进一步挖掘白灵片治疗白癜风的潜在共同靶点。对白灵片的有效成分和作用靶点的数据进行收集整理,导入Cytoscape 3.10.2软件,构建“白灵片-活性成分-作用靶点”的交互关系网络。利用STRING数据库和Cytoscape软件构建“白灵片-白癜风关键靶点”的蛋白质-蛋白质互作(protein-protein interaction, PPI)核心网络可视化分析。运用DAVID数据库对白灵片治疗白癜风的潜在靶点进行基因本体(Gene Ontology, GO)功能及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes, KEGG)通路富集分析。结果 筛选出27个白灵片主要成分的活性化合物,220个药物靶点,1500个疾病靶点和74个交集靶点。中药-活性成分-靶点网络图显示,白灵片主要成分的核心活性化合物可能为槲皮素、山奈酚、7-O-甲基异微凸剑叶莎醇、芒柄花黄素、β-谷甾醇。针对白灵片-白癜风关键靶点构建PPI网络,发现白灵片治疗白癜风的关键靶点基因包括蛋白激酶B(AKT1)、肿瘤坏死因子(TNF)、白细胞介素6(IL6)、肿瘤蛋白p53(TP53)、白细胞介素-1β(IL1B)、胱天蛋白酶3(CASP3)、B淋巴细胞瘤-2蛋白(BCL2)、人雌激素受体(ESR1)、前列腺素氧化环化酶2(PTGS2)、过氧化物酶体增殖物激活受体γ(PPARG)等。GO功能富集分析得到条目数602个,其中生物过程条目495个,细胞组成条目38个,分子功能条目69个。KEGG通路富集分析得到信号通路155条,主要涉及癌症相关通路、脂质与动脉粥样硬化、流体剪切应力与动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路、细胞衰老、人T细胞白血病病毒1型感染、IL-17信号通路等领域。结论 白灵片可能通过多成分、多靶点、多通路治疗白癜风。
Abstract
Objective To explore the mechanism of action of Bailing tablets(BLT) in the treatment of vitiligo with nework pharmacology methods. Methods The effective active compounds and target genes of BLT were retrieved, collected, and screened using the TCMSP (Traditional Chinese Medicine System Pharmacology Database and Analysis Platform) and UniProt database platform. The related pathogenic genes of vitiligo were queried through the DisGeNET, OMIM, and GeneCards databases, and the potential common targets for the treatment of vitiligo by BLT were further explored. The data of the active components and action target of BLT were collected and sorted, and then imported into Cytoscape 3.10.2 software to construct an “interaction network of Bailing tablet-active compounds-target genes”. The “protein-protein interaction (PPI) core network visualization analysis of Bailing tablet-key targets of vitiligo” was constructed using the STRING database and Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the potential targets of BLT in the treatment of vitiligo using the DAVID database. Results A total of 27 active compounds of main components of BLT, 220 drug targets, 1,500 disease targets, and 74 overlapping targets were screened out. The network diagram of “Chinese medicine-active compounds-target” showed that the core active compounds of the main components of BLT might be quercetin, kaempferol, 7-O-methylisomucronulatol, formononetin, and β-sitosterol. The PPI network was constructed for the key targets of Bailing tablet-vitiligo, and it was found that the key target genes for BLT to treat vitiligo included protein kinase B (AKT1), tumor necrosis factor (TNF), interleukin 6 (IL6), tumor protein p53 (TP53), interleukin-1β (IL1B), caspase 3 (CASP3), B lymphocyte tumor-2 protein (BCL2), human estrogen receptor (ESR1), prostaglandin oxygenase 2 (PTGS2), peroxisome proliferator-activated receptor γ (PPARG), etc. The GO functional enrichment analysis yielded 602 terms, including 495 biological processes, 38 cellular components, and 69 molecular functions. The KEGG pathway enrichment analysis yielded 155 signaling pathways, mainly involving cancer-related pathways, lipid and atherosclerosis, fluid shear stress and atherosclerosis, the AGE-RAGE signaling pathway in diabetes complications, cell aging, human T-cell leukemia virus type 1 infection, the IL-17 signaling pathway, etc. Conclusions BLT may treat vitiligo through multiple components, multiple targets, and multiple pathways.
关键词
白灵片 /
白癜风 /
作用机制 /
网络药理学 /
中药
Key words
Bailing tablet /
vitiligo /
mechanism of action /
network pharmacology /
traditional Chinese medicine
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