采用网络药理学和生物信息学方法,从铁性凋亡的角度研究葛根素治疗骨关节炎的分子机制,揭示了一个新的治疗目标。从FerrDb获得铁凋亡相关靶标。从TCMSP中检索葛根素作用靶标,Pharmmappe,SwissTargetPrediction,和Targetnet数据库,并补充了PubMed。GSE12021,GSE55235和GSE82107的基因表达谱是使用“骨关节炎”作为GEO数据库中的搜索词获得的,并对骨关节炎进行差异表达基因筛选分析。葛根素之间的交叉目标,铁死亡,和骨关节炎是使用维恩图获得的。采用R软件进行GO和KEGG分析。使用AutodockVina和PyMol软件进行葛根素和核心靶标的分子对接和可视化。葛根素对细胞活力和TNFα的影响,在体外实验中测试了人炎症关节软骨细胞的IL6和ILβ水平。葛根素,铁性凋亡,和骨关节炎共享四个目标:PLIN2,PTGS2,VEGFA,IL6GO富集分析显示葛根素维持血脑屏障,调节肽丝氨酸磷酸化,并有抗炎作用。KEGG分析显示葛根素的抗炎作用主要通过VEGF,IL-17,C型凝集素受体,HIF-1,TNF,和其他信号通路。葛根素紧密结合PLIN2、PTGS2、VEGFA、和分子对接中的IL6靶标。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葛根素多靶点、多途径治疗OA,这可能与铁性死亡有关,并证实了其抗炎作用。
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.