基于网络药理学和分子对接技术解读川皮苷改善代谢综合征的作用机制（英文）

采用网络药理学方法探讨川皮苷改善代谢综合征的作用机制。首先利用TCMSP、TCMIP、TCMID、ETCM、HERB、NPASS和NPACT等数据库获取川皮苷作用靶点;在Dis Ge NET、Drug Bank等6个数据库中获取代谢综合征的相关靶点,筛选出与川皮苷作用靶点的共同部分构建PPI网络,并利用R语言对交集靶点进行GO和KEGG通路富集分析;最后对川皮苷和关键疾病靶点进行分子对接验证。结果收集到川皮苷作用靶点105个,代谢综合征相关靶点1975个。上述靶点取交集,获得了60个川皮苷改善代谢综合征的潜在靶点。PPI分析发现,川皮苷改善代谢综合征的关键靶点为TP53、MAPK8、AKT1、GSK3B、HSP90AA1、CTNNB1、JUN、AR、ESR1、CCND1、HRAS、TNF和PPARA。功能富集分析发现,脂质和动脉粥样硬化通路及糖尿病并发症中的AGE-RAGE信号通路在川皮苷改善代谢综合征过程中发挥重要作用。分子对接结果显示,川皮苷与上述13个核心基因具有很强的亲和力。综上所述,推测川皮苷通过脂质和动脉粥样硬化通路及糖尿病并发症中的AGE-RAGE信号通路发挥改善代谢综合...

Deciphering the latent mechanism of nobiletin in the treatment of metabolic syndrome based on network pharmacology and molecular docking

Nobiletin (NOB) may have a potential effect on metabolic syndrome. In the present study, we aimed to explore the latent mechanisms of NOB for the treatment of metabolic syndrome based on network pharmacology and molecular docking methods. The potential targets of NOB were retrieved and identified from six databases, such as the Traditional Chinese Medicine Systems Pharmacology Database. The metabolic syndrome-related targets were retrieved from six databases as follows: the DrugBank database, GeneCards database, the Online Mendelian Inheritance in Man database, PharmGKB database, Therapeutic Target Database, and DisGeNet database. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of 60 intersected genes were performed in R software (Bioconductor, clusterProfiler) to investigate the molecular mechanisms. Subsequently, the ingredient-target-pathway network of NOB was constructed and visualized through Cytoscape 3.8.0 software. Protein-protein interaction network was constructed to screen hub genes in the treatment of NOB on metabolic syndrome through The Search Tool for the Retrieval of Interacting Genes/Proteins and visualized by Cytoscape 3.8.0 software. Afterward, molecular docking was used to analyze the score of the hub genes with NOB. Cumulatively, 105 targets of NOB were identified. Moreover, 1975 metabolic syndrome-related genes were acquired from six databases after combining and deleting the repeated items, and the overlap of metabolic syndrome-related genes with NOB-related target genes identified 60 intersection genes of NOB against metabolic syndrome. Moreover, 1858 GO entries of NOB on metabolic syndrome were identified, and 153 pathways were screened based on GO and KEGG analyses. The target hub genes of NOB in MetS treatment were TP53, MAPK8, AKT1, GSK3B, HSP90AA1, CTNNB1, JUN, AR, ESR1, CCND1, HRAS, TNF, and PPARA. It was confirmed that lipid and atherosclerosis, together with the AGE-RAGE signaling pathway in diabetic complications, were putatively critical pathways of NOB in the treatment of metabolic syndrome. The molecular docking results revealed that most of 13 hub genes had a strong binding to NOB. Due to the versatile actions of NOB, it had the potential action on metabolic syndrome by multiple targets and multiple pathways.