类风湿性关节炎（RA）是一种全球流行率较高的难以治愈的关节疼痛性疾病，严重影响人们的生活水平。长期以来，蜜蜂毒素一直被用于治疗RA，并取得了良好的效果。蜜蜂毒素主要活性成分之一为蜜蜂毒素，但其在治疗RA中的分子机制尚不清楚。从相关数据库获取潜在的蜜蜂毒素和RA靶标，并筛选出蜜蜂毒素和RA的共同靶标。使用STRING数据库构建PPI网络，根据可视化结果筛选出核心靶标。通过基因本体功能注释和KEGG（Kyoto Encyclopedia of Genes and Genomes）通路对核心靶标进行富集分析。最后，通过模拟分子对接评估蜜蜂毒素与靶蛋白的结合情况，以验证网络药理学预测结果的可靠性。 总共从相关数据库获得了138个蜜蜂毒素靶标和5795个RA靶标，通过取交集得到90个共同靶标。筛选出了STAT3、AKT1、肿瘤坏死因子和JUN等18个核心靶标。富集分析结果表明，蜜蜂毒素主要通过肿瘤坏死因子、白细胞介素-17、Toll样受体和高级糖基化终产物-RAGE信号通路以及致病菌感染等途径发挥抗RA作用。分子对接结果表明，蜜蜂毒素与核心靶蛋白有良好的结合活性。 蜜蜂毒素治疗RA是多靶点和多途径相互作用的结果。本研究为进一步探索蜜蜂毒素在RA治疗中提供了理论基础和科学依据。版权所有 © 2023 作者。Wolters Kluwer Health出版。

Rheumatoid arthritis (RA) is a type of difficult-to-cure arthralgia with a worldwide prevalence. It severely affects people's living standards. For a long time, bee venom has been used to treat RA and has shown good results. Melittin is the main active component of bee venom used for RA treatment, but the molecular mechanism of melittin in RA treatments remains unclear.Potential melittin and RA targets were obtained from relevant databases, and common targets of melittin and RA were screened. The STRING database was used to build the PPI network and screen the core targets after visualization. The core targets were enriched by Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway. Finally, the binding of melittin to target proteins was evaluated through simulated molecular docking, which verified the reliability of the prediction results of network pharmacology.In total, 138 melittin targets and 5795 RA targets were obtained from relevant databases, and 90 common targets were obtained through intersection. Eighteen core targets, such as STAT3, AKT1, tumor necrosis factor, and JUN, were screened out. Enrichment analysis results suggested that melittin plays an anti-RA role mainly through tumor necrosis factor, interleukin-17, toll-like receptors, and advanced glycation end products-RAGE signaling pathways, and pathogenic bacterial infection. Molecular docking results suggested that melittin has good docking activity with core target proteins.RA treatment with melittin is the result of a multi-target and multi-pathway interaction. This study offers a theoretical basis and scientific evidence for further exploring melittin in RA therapy.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.