基于网络药理学探索土茯苓治疗下肢动脉硬化闭塞症的作用机制

Mechanism of Smilax glabra Rhizoma in Treatment of Arteriosclerosis Obliterans of Lower Extremities Based on Network Pharmacology

摘要: 目的：基于网络药理学分析土茯苓治疗下肢动脉硬化闭塞症的作用机制。方法：通过中药系统药理学数据库分析平台(The Traditional Chinese Medicine Database Analysis Platform, TCMSP)获取土茯苓的主要活性成分。以TCMSP预测的活性成分为基础，通过UniProt数据库转换获取作用靶点；从GeneCards、OMIM、TTD、DisGeNET以及DrugBank数据库检索获得ASO相关疾病靶点；取交集获得土茯苓与ASO的共同靶点；STRING数据库对共同靶点进行蛋白–蛋白相互作用(Protein-Protein Interaction Network, PPI)分析、Cytoscape 3.9.1软件构建PPI网络；采用Metascape平台对核心靶点进行GO富集分析与KEGG信号通路富集分析，并利用微生信在线绘图平台进行可视化处理。结果：从土茯苓中筛选得到15种活性成分及194个作用靶点，与相关靶点取交集，得到124个共同靶点；土茯苓治疗的有效活性成分有β-谷甾醇、柚皮素、豆甾醇、花旗松素、槲皮素、薯蓣皂素、新落新妇苷等。糖尿病并发症中的AGE-RAGE信号通路、脂质和动脉粥样硬化、TNF信号通路等通路可能为下肢动脉硬化闭塞症的潜在核心信号通路。结论：土茯苓治疗ASO具有多成分、多靶点、多通路的特点，这为其后续实验和临床研究提供了理论基础。

Abstract: Objective: To analyze the mechanism of action of Smilax glabra rhizoma in the treatment of lower limb atherosclerosis-occlusive disease based on network pharmacology. Methods: The main active ingredients of Smilax glabra rhizoma were obtained from the Traditional Chinese Medicine Database Analysis Platform (TCMSP). The active ingredients predicted by TCMSP were used as the basis to obtain the active targets through UniProt database conversion. ASO-related disease targets were retrieved from GeneCards, OMIM, TTD, DisGeNET and DrugBank databases. The common targets of Smilax glabra and ASO were obtained by intersection. STRING database was used to analyze the protein-protein interaction net-work (PPI) of common targets. The PPI network was constructed using Cytoscape 3.9.1 software; the core targets were enriched with GO and KEGG signaling pathways using the Metascape platform and visualized using the Microbiology online mapping platform. The results Results: 15 active ingredients and 194 targets were screened from Smilax glabra rhizoma and intersected with related targets to obtain 124 common targets; the active ingredients of Smilax glabra rhizoma were β-sitosterol, naringenin, dousterol, daidzein, quercetin, diosgenin and neolaxoside. The AGE-RAGE signaling pathway, lipid and atherosclerosis, and TNF signaling pathway in diabetic complications may be potential core signaling pathways in lower limb atherosclerotic occlusive disease. Conclusion: The multi-component, multi-target, and multi-pathway characteristics of fucoidan in the treatment of ASO provide a theoretical basis for its subsequent experimental and clinical studies.