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基于网络药理学探索甘露饮药方治疗复发性口腔溃疡的作用机制
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Abstract:
目的：运用网络药理学的方法探索甘露饮药方治疗复发性口腔溃疡(Recurrent Oral Ulcer, ROU)的活性成分及作用机制。方法：通过中药系统药理学数据库与分析平台(TCMSP)、BATMAN-TCM获取甘露饮药方单味中药有效成分及相关靶点，利用PubChem、NovoPro等数据库进行活性成分靶点预测并用UniProt数据库矫正靶点，利用人类基因数据库GeneCards筛选复发性口腔溃疡的疾病靶点，采用Venny 2.1工具将药物靶点和疾病靶点做交集，通过STRING数据库和Cytoscape 3.10.1软件绘制中药–成分–靶点网络以及蛋白相互作用(PPI)网络，使用Metascape数据库进行GO富集分析和KEGG通路富集分析。结果：共筛选出166个活性成分，与疾病交集靶点278个。主要活性成分包括光甘草定、苏荠黄酮、黄芩新素、黄芩黄酮、去甲汉黄芩素、槲皮素、异鼠李素、山奈酚等；PPI靶点预测出的核心靶点共10个，包括STAT3，SRC，PIK3CA，PIK3R1，PIK3CD，AKT1，EGFR，HSP90AA1，ESR1，PTPN11；KEGG富集分析显示，与甘露饮治疗复发性口腔溃疡有关的通路包括化学致癌–受体激活通路、癌症中的蛋白聚糖、催乳素信号通路、幽门螺杆菌感染中的上皮细胞信号传导、脂肪细胞因子信号通路等。结论：初步验证了甘露饮治疗复发性口腔溃疡药效基础，可为复发性口腔溃疡治疗提供理论基础。
Objective: To explore the active ingredients and mechanism of action of Ganluyin prescription in the treatment of recurrent oral ulcer (ROU) by using the method of network pharmacology. Methods: we obtained the active ingredients and related targets of the single Chinese herbal medicine of Ganluyin prescription through TCMSP and BATMAN-TCM databases, and predicted the active ingredient targets using PubChem database, NovoProdatabas and target correction using UniProt database. The human gene database GeneCards was used to screen the disease targets of recurrent oral ulcer. Venny 2.1 tool was used to intersect the drug targets and disease targets, and the STRING database and Cytoscape 3.10.1 software were used to draw the traditional Chinese medicine-ingredient-target network and the protein-protein interaction (PPI) network. The Metascape database was used to analyze the enrichment of the GO and KEGG pathways. Results: A total of 166 active ingredients were screened, 278 targets intersecting with diseases. The main active ingredients were glabridin, moslosooflavone, neobaicalein, panicolin, norwogonin, quercetin, isorhamnetin, and kaempferol, etc. A total of 10 core targets were predicted for PPI targets, including STAT3, SRC, PIK3CA, PIK3R1, PIK3CD, AKT1, EGFR, HSP90AA1, ESR1, PTPN11. The KEGG enrichment analysis showed that the related to Ganluyin prescription for the treatment of recurrent oral ulcer pathways including chemical carcinogenesis - receptor activation, proteoglycans in cancer, prolactin signaling pathway, epithelial cell signaling in helicobacter pylori infection, adipocytokine signaling pathway, etc. Conclusion: The preliminary validation of the pharmacodynamic basis of Ganluyin prescription for the treatment of recurrent oral ulcer can provide a theoretical basis for the treatment of recurrent oral ulcers.
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