为揭示豨莶草治疗类风湿关节炎（rheumatoid arthritis, RA）的分子机制，通过随机森林（random forest, RF）模型在数据集GSE100191和GSE17755上筛选出核心靶点，并对核心靶点进行单样本基因集富集分析（single-sample gene set enrichment analysis, ssGSEA）。豨莶草的化学成分基于TCMSP数据库下载，化合物的优化基于SYBYL2.1.1能量最小化，采用分子对接分析豨莶草化合物与YTHDC1、IGFBP2基因的结合情况，结果以总分值（T_Score）为阈值进行分析。结果表明：通过构建的RF模型确定胰岛素样生长因子结合蛋白2 （insulin-like growth factor binding protein 2, IGFBP2）、YTHDC1 （YTH N6-methyladenosine RNA binding protein C1）、AlkB同系物5（AlkB Homolog 5, ALKBH5）、癌症中的胰岛素样生长因子2 mRNA结合蛋白1（insulin like growth factor 2 MRNA binding protein 1, IGF2BP1）为核心基因，其中IGFBP2是最显著的基因，其次为YTHDC1、ALKBH5、IGF2BP1。与正常对照组相比，ALKBH5、YTHDC1、IGFBP2、IGF2BP1在RA中高表达，具有显著性差异（P<0.05）。IGFBP2基因与多种免疫细胞相关，IGFBP2表达增大，多种免疫细胞的数量显著增加，导致免疫过度激活的微环境。通过分子对接发现豨莶草31个化合物，14个化合物与IGFBP2有较好的结合，12个化合物与YTHDC1有较好的结合，其中豨莶苷为治疗RA的关键物质基础。可见豨莶草治疗RA的作用机制可能与免疫系统相关，抑制免疫过度激活，防止炎症风暴的发生。

To reveal the molecular mechanism of Siegesbeckia orientalis L. in treating rheumatoid arthritis (RA), core targets were screened out through the random forest (RF) model on the datasets GSE100191 and GSE17755. Perform single sample gene set enrichment analysis (ssGSEA) on core targets. The chemical composition of Siegesbeckia orientalis L. was downloaded from the TCMSP database, and the optimization of compounds was based on SYBYL2.1.1 energy minimization. Molecular docking analysis was used to investigate the binding of Siegesbeckia orientalis L. compounds to YTHDC1 and IGFBP2 genes. The results were analyzed by total score(T_Score) as the threshold. The results show these as follows. The constructed RF model was used to Insulin-like growth factor binding protein 2 (IGFBP2), YTH N6-methyladenosine RNA binding protein C1(YTHDC1), AlkB Homolog 5 (ALKBH5), insulin like growth factor 2 MRNA binding protein 1(IGFBP2), with IGFBP2 being the most significant gene, followed by YTHDC1, ALKBH5, and IGF2BP1. Compared with the normal control group, ALKBH5, YTHDC1, IGFBP2, and IGF2BP1 were highly expressed in RA, with significant differences (P < 0.05). The IGFBP2 gene is associated with various immune cells, and an increase in IGFBP2 expression leads to a significant increase in the number of multiple immune cells, resulting in a microenvironment of immune overactivation. Through molecular docking, 31 compounds of Siegesbeckia orientalis L. were discovered, with 14 compounds showing good binding to IGFBP2 and 12 compounds showing good binding to YTHDC1. Among them, darutoside is the key substance basis for treating RA. It can be seen that the mechanism of action of Siegesbeckia orientalis L. in treating RA may be related to the immune system, inhibiting immune overactivation and preventing the occurrence of inflammatory storms.