Potential Mechanisms of Yanghe Decoction in the Treatment of Soft Tissue Sarcoma and Arteriosclerosis Obliterans Based on Network Pharmacology

基于网络药理学探讨阳和汤对软组织肉瘤和动脉硬化闭塞症“异病同治”的作用机制

Objective The objective of this study was to investigate potential mechanisms of Yanghe Decoction(YHD)in treating soft tissue sarcoma(STS)and arteriosclerosis obliterans(ASO)based on the use of network pharmacology.Methods Candidate compounds and potential targets were identifed through the TCM Systems Pharmacology database and a comprehensive literature search.Related targets of STS and ASO were collected in the GeneCards database,DisGeNET database,and Drugbank database.Furthermore,The STRING 11.0 database was used to determine protein-protein interaction(PPI)networks;common targets were obtained and imported into Cytoscape 3.7.2.Then,a PPI network comprising common targets was drawn,and network topology analysis was performed to screen for key shared targets.Gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of key shared targets were performed by using Metascape software.Subsequently.a compound-target-pathway network was constructed via Cytoscape 3.7.2.Results The following signaling pathways were found to be associated with the mechanisms of YHD in treating STS and ASO:AGE-RAGE signaling pathway,IL-17 signaling pathway;HIF-1 signaling pathway,TNF signaling pathway,interactions between cytokines and cytokine receptors,Th17 cell differentiation,and NOD-like receptor signaling pathway.Among the compounds and targets involved in these pathways,quercetin,luteolin,and kaempferol were found to be core compounds,and TNF,IL-6,and MAPK1 were found to be core targets.Conclusion Taken together,our findings elucidated that potential mechanisms of YHD in treating STS and ASO involved cellular proliferation/differentiation,angiogen-esis,inflammation,immune responses,oxidative stress,and other related signaling pathways.

目的:在中医学对疾病病因病机认识的指导下,通过网络药理学方法探讨阳和汤“异病同治”软组织肉瘤和动脉硬化闭塞症的作用机制,为中医学“异病同治”理论提供现代医学证据。方法:通过TCMSP数据库及文献检索获取候选化合物及化合物潜在作用靶点,在GeneCards数据库、DisGeNET数据库、Drugbank数据库搜集软组织肉瘤和动脉硬化闭塞症的相关疾病靶点,找到化合物与两种疾病的共有靶点;通过STRING 11.0数据库,得出共有靶点的蛋白质间相互作用关系并导入Cytoscape 3.7.2绘制共有靶点蛋白质间相互作用网络并进行网络拓扑分析,筛选出关键共有靶点;采用Metascape对关键共有靶点进行G0功能富集分析及KEGG通路富集分析,并构建“化合物-靶点-通路”网络图。结果:本研究通过网络药理学方法筛选出阳和汤“异病同治”软组织肉瘤和动脉硬化闭塞症的重要信号通路有AGE-RAGE信号通路、IL-17信号通路、HIF-1信号通路、TNF信号通路、细胞因子与细胞因子受体的相互作用、Th17细胞分化、NOD样受体信号通路;在参与这些通路的化合物和靶点中,槲皮素、木樨草素、山奈酚是本研究的核心化合物;TNF、IL-6、MAPK1是本研究的核心靶点。结论:本研究揭示了阳和汤“异病同治”软组织肉瘤和动脉硬化闭塞症的机制主要涉及细胞增殖、分化,血管生成,炎症,免疫应答,氧化应激等相关的信号通路,为后期的实验研究提供参考。