Table7_Network Pharmacology and Molecular Docking to Elucidate the Potential Mechanism of Ligusticum Chuanxiong Against Osteoarthritis.xlsx

Background: Osteoarthritis (OA) is a degenerative disease which serious affects patients. Ligusticum chuanxiong (CX) has been shown to have a certain curative effect on osteoarthritis in traditional Chinese medicine therapy. This study is based on network pharmacology and molecular docking technology to explore the potential mechanism of CX.
Methods: Components of CX to treat osteoarthritis were screened in the TCMSP database and targets were predicted by the PharmMapper database, the osteoarthritis targets were collected from the GeneCards database, and intersection genes were found to be the possible targets of CX anti-OA. The STRING database and Cytoscape software were utilized for protein-protein interaction analysis and further screening of core targets. The Metascape database was used for KEGG and GO enrichment analyses. Then, the top 10 pathways were selected to construct “drug-compound-target-pathway-disease” network analysis. Finally, molecular docking was used to analyze the binding affinity of seven compounds with core targets and TNF-α.
Results: Seven compounds with 253 non-repetitive targets of CX were screened from the TCMSP database and 60 potential intersection targets of CX anti-OA were found. PPI network analysis showed that the core targets were ALB, AKT1, IGF1, CASP3, MAPK1, ANXA5, and MAPK14, while GO and KEGG pathway enrichment analyses showed that the relevant biological processes involved in the treatment of osteoarthritis by CX might include the MAPK cascade and reactive oxygen species metabolic process. The KEGG pathway analysis result was mainly associated with the MAPK signaling pathway and PI3K-AKT signaling pathway. We further docked seven ingredients with MAPK1 and MAPK14 enriched in the MAPK pathway, and TNF-α as the typical inflammatory cytokine. The results also showed good binding affinity, especially FA, which may be the most important component of CX anti-OA.
Conclusion: Our research revealed the potential mechanism of CX in the treatment of OA, and our findings can also pave the way for subsequent basic experimental verification and a new research direction.

背景：骨关节炎（Osteoarthritis, OA）是一种严重影响患者健康的退行性疾病。在中医治疗体系中，川芎（Ligusticum chuanxiong, CX）对骨关节炎具有一定临床疗效。本研究基于网络药理学与分子对接技术，探究川芎治疗骨关节炎的潜在作用机制。
方法：从TCMSP数据库中筛选川芎治疗骨关节炎的活性成分，并通过PharmMapper数据库预测其潜在作用靶点；从GeneCards数据库获取骨关节炎相关靶点，取二者的交集基因作为川芎抗骨关节炎的潜在作用靶点。利用STRING数据库与Cytoscape软件开展蛋白质-蛋白质相互作用（Protein-Protein Interaction, PPI）分析，并进一步筛选核心靶点；通过Metascape数据库进行基因本体（Gene Ontology, GO）与京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）富集分析，选取排名前十的通路构建“药物-成分-靶点-通路-疾病”网络开展分析。最后采用分子对接技术，分析七种活性成分与核心靶点及肿瘤坏死因子-α（TNF-α）的结合亲和力。
结果：从TCMSP数据库中共筛选得到川芎的7种活性成分与253个非重复靶点，同时获得60个川芎抗骨关节炎的潜在交集靶点。PPI网络分析显示核心靶点包括ALB、AKT1、IGF1、CASP3、MAPK1、ANXA5及MAPK14；GO与KEGG通路富集分析表明，川芎治疗骨关节炎所涉及的相关生物学过程可能包括丝裂原活化蛋白激酶（Mitogen-Activated Protein Kinase, MAPK）级联反应与活性氧代谢过程。KEGG通路分析结果主要与MAPK信号通路及PI3K-AKT信号通路相关。本研究进一步将7种活性成分与MAPK通路富集得到的MAPK1、MAPK14以及典型炎症细胞因子TNF-α进行分子对接，结果显示二者均具有良好的结合亲和力，其中FA可能是川芎抗骨关节炎的核心活性成分。
结论：本研究揭示了川芎治疗骨关节炎的潜在作用机制，研究结果可为后续基础实验验证提供依据，并为相关领域研究指明新方向。