Network pharmacology and bioinformatics were used to study puerarin’s molecular mechanism in treating osteoarthritis from the perspective of ferroptosis, revealing a new treatment target. Ferroptosis-related targets were obtained from FerrDb. Puerarin action targets were retrieved from TCMSP, Pharmmappe, SwissTargetPrediction, and Targetnet databases, and supplemented with PubMed. The gene expression profiles of GSE12021, GSE55235, and GSE82107 were obtained using “Osteoarthritis” as the search term in the GEO database, and the differential expression gene screening analysis was performed for osteoarthritis. The intersection targets between puerarin, iron death, and osteoarthritis were obtained using Venn diagrams. GO and KEGG analyses were conducted with R software. Molecular docking and visualization of puerarin and core targets were performed using Autodock Vina and PyMol software. The effects of puerarin on the cell viability and the TNFα, IL6, and Ilβ levels of human inflammation articular chondrocytes were tested in vitro experiments. Puerarin, ferroptosis, and osteoarthritis share four targets: PLIN2, PTGS2, VEGFA, and IL6. GO enrichment analysis showed that puerarin maintained the blood-brain barrier, regulated peptide serine phosphorylation, and had anti-inflammatory effects. KEGG analysis showed that puerarin’s anti-inflammatory effects were mainly through VEGF, IL-17, C-type lectin receptor, HIF-1, TNF, and other signaling pathways. Puerarin closely bound PLIN2, PTGS2, VEGFA, and IL6 targets in molecular docking. In vitro, puerarin prevented osteoarthritis. Network pharmacology and bioinformatics explained puerarin’s multi-target and multi-pathway treatment of OA, which may be related to ferroptosis, and confirmed its anti-inflammatory effect.

利用网络药理学和生物信息学从铁死亡的角度研究葛根素治疗骨关节炎的分子机制，揭示新的治疗靶点。铁死亡相关靶标是从 FerrDb 获得的。葛根素作用靶点从 TCMSP、Pharmmappe、SwissTargetPrediction 和 Targetnet 数据库中检索，并用 PubMed 进行补充。在GEO数据库中以“骨关节炎”为检索词获取GSE12021、GSE55235、GSE82107的基因表达谱，并对骨关节炎进行差异表达基因筛选分析。使用维恩图获得葛根素、铁死亡和骨关节炎之间的交叉目标。使用R软件进行GO和KEGG分析。使用 Autodock Vina 和 PyMol 软件进行葛根素和核心靶点的分子对接和可视化。体外实验测试了葛根素对人炎症关节软骨细胞活力和TNFα、IL6和Ilβ水平的影响。葛根素、铁死亡和骨关节炎有四个共同靶点：PLIN2、PTGS2、VEGFA 和 IL6。 GO富集分析表明葛根素具有维持血脑屏障、调节肽丝氨酸磷酸化和抗炎作用。 KEGG分析显示，葛根素的抗炎作用主要是通过VEGF、IL-17、C型凝集素受体、HIF-1、TNF等信号通路发挥作用。葛根素在分子对接中与 PLIN2、PTGS2、VEGFA 和 IL6 靶标紧密结合。在体外，葛根素可以预防骨关节炎。网络药理学和生物信息学解释了葛根素对OA的多靶点、多途径治疗可能与铁死亡有关，并证实了其抗炎作用。