目的:基于网络药理学和分子对接探讨“黄芪桂枝五物汤”治疗奥沙利铂致周围神经病变(oxaliplatin-induced peripheral neuropathy, OIPN)的作用机制。方法:利用Traditional Chinese Medicine System Pharmacology(TCMSP)数据库、Swiss Target Prediction数据库、Therapeutic Target Database(TTD)数据库、Traditional Chinese Medicine Information Database(TCMID)数据库及查阅相关文献筛选黄芪、桂枝、芍药、生姜、大枣活性成分和相关靶点,通过UniProt数据库进行靶点标准化;运用Cytoscape(V3.9.1)软件构建活性成分-靶点网络;通过GeneCards数据库检,OIPN相关基因;利用STRING数据库构建蛋白互作网络图;通过R语言软件(V3.6.1)和Bioconductor数据库对潜在靶点进行基因本体(gene ontology, GO)生物学功能注释和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;最后通过分子对接技术将核心活性成分与核心靶点进行对接。结果:筛选后得到黄芪桂枝五物汤共141个活性成分,196个药物靶点,核心靶点有TNF、IL6、IL1B、AKT1、CXCL12等;GO分析得到233个相关生物过程,KEGG分析得到112条信号通路,分子对接结果显示核心成分与核心靶点具有较好的结合能。结论:“黄芪桂枝五物汤”通过多个靶点、多条通路来发挥治疗奥沙利铂致周围神经病变的作用,为“黄芪桂枝五物汤”的临床应用及相关疾病的临床研究提供理论依据。
Objective: To explore the mechanism of Huangqi Guizhi Wuwu Decoction in the treatment of oxaliplatin-induced peripheral neuropathy (OIPN) based on network pharmacology and molecular docking. Methods: Traditional Chinese Medicine System Pharmacology (TCMSP), SwissTargetPrediction Database, Therapeutic Target Database (TTD), Traditional Chinese Medicine Information Database (TCMID), and literature review were used to screen the active ingredients and related targets of Astragali Radix, Cinnamomi Ramulus, Paeonia, Zingiber officinale Roscoe, Jujubae Fructus. Target standardization was carried out by UniProt Database. Cytoscape (V3.9.1) software was used to construct the active ingredient-target network. OIPN related genes were retrieved from GeneCards database. The protein interaction network map was constructed using the STRING database. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of potential targets were carried out by R language software and Bioconductor database. Finally, the core active ingredient was docked with the core target by molecular docking technology. Results: After screening, a total of 141 active ingredients and 196 drug targets of Huangqi Guizhi Wuwu Decoction were obtained. The core targets were TNF, IL6, IL1 B, AKT1, CXCL12, etc.; A total of 233 related biological processes were obtained by GO analysis, and 112 signaling pathways were obtained by KEGG analysis. Molecular docking results showed that the core components had good binding energy with the core targets. Conclusion: Huangqi Guizhi Wuwu Decoction in the treatment of OIPN is the result of multi-component, multi-target and multi-pathway interaction, which provides certain theoretical basis for the clinical application and clinical research on OIPN related diseases.
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