基于网络药理学和分子对接研究太子参治疗骨关节炎的作用机制

Study on the mechanism of action of Radix Pseudostellariae in the treatment of osteoarthritis based on network pharmacology and molecular docking

目的 基于网络药理学和分子对接研究太子参对骨关节炎(OA)关键靶蛋白的作用机制。方法 使用TCMSP平台检索太子参的活性成分并预测作用靶点,筛选Gene Cards、Drug Bank、Pharm Gkb、OMIM数据库中OA的相关基因并进行合并。得到的疾病共有靶点通过STRING数据库将疾病与药物交集靶点进行蛋白质-蛋白质相互作用(PPI)分析,并将结果输入Cytoscape 3.8.2软件进行分析,然后,使用Cytoscape 3.8.2软件构建药物-活性成分-靶点网络图,以获得药物-其他疾病交叉靶点中的核心关键蛋白。将绘制的PPI网络导入Cytoscape 3.8.2软件中,并使用CytoNCA插件对网络进行筛选。利用R语言对OA与太子参药物的交集进行基因本体(GO)功能分析和京都基因组和基因组学百科全书(KEGG)通路分析,得到GO及KEGG富集分析结果。通过PubChem数据库下载PPI网络核心靶标对应的小分子配体3D结构的SDF文件,利用“1-CLICK DOCKING”在线工具进行分子对接,下载PDB结果文件再用Discovery Studio软件绘制残基-配体交互情况。结果 本研究预测太子参治疗OA的活性成分25个,靶点57个,关键活性成分包括木犀草素等5个活性成分,经过两次筛选得到核心靶点为MAPK1、CCND1、JUN、TP53、CASP3、BCL2L1、AKT1、EGFR;GO和KEGG分析结果显示,太子参通过以上关键靶点,影响PI3K-Akt、白细胞介素-17(IL-17)信号通路等6个主要通路,在预防和治疗OA中发挥作用;分子对接验证木犀草素与关键靶点EGFR、CAP3、AKT1、TP53的结合性最好。结论 本研究揭示了太子参通过多途径、多靶点防治OA的作用,为进一步研究其防治OA作用提供了基础。

Objective To study the mechanism of action of Radix Pseudostellariae on key target proteins in osteoarthritis(OA) based on network pharmacology and molecular docking.Methods The TCMSP platform was used to retrieve the active ingredients of Radix Pseudostellariae and predict the action targets,genes related to OA in Gene Cards,Drug Bank,Pharm Gkb,and OMIM databases were screened,and then merged.The common targets of the disease were obtained and the protein-protein interaction(PPI)analysis was conducted on the intersection targets of the disease and drugs through the STRING database,and the results were inputted into Cytoscape 3.8.2 software for analysis.Then,a drug-active ingredienttarget network diagram was constructed using Cytoscape 3.8.2 software to obtain the core key proteins in the drug-other disease intersection targets.The drawn PPI network was imported into Cytoscape 3.8.2 software and the network was filtered using the CytoNCA plugin.R language was used to perform gene ontology(GO) functional analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis on the intersection of OA disease and Radix Pseudostellariae drugs,and GO and KEGG enrichment analysis results were obtained.The SDF file of the small molecule ligand 3D structure corresponding to the core target of the PPI network was downloaded through the PubChem database,the "1-CLICK DOCKING" online tool was used for molecular docking,the PDB result file was downloaded,and then the Discovery Studio software was used to draw the residue-ligand interaction situation.Results The study predicted that there were 25 active ingredients and 57 targets for the treatment of OA by Radix Pseudostellariae,with 5 key active ingredients including luteolin.After two screenings,the core targets obtained were MAPK1,CCND1,JUN,TP53,CASP3,BCL2L1,AKT1,EGFR.The results of GO and KEGG analysis showed that Radix Pseudostellariae affected six main pathways,including the PI3K-Akt signaling pathway,and interleukin-17(IL-17) signaling pathway through the above key targets,playing a role in the prevention and treatment of OA.Molecular docking verification shows that luteolin has the best binding ability with key targets such as EGFR,CAP3,AKT1,and TP53.Conclusion This study reveals the role of Radix Pseudostellariae in the prevention and treatment of OA through multiple pathways and targets,providing a basis for further study on its preventive and therapeutic effects on OA.