College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, Hunan, China.
Department of Rehabilitation and Healthcare, Hunan University of Medicine, Huaihua, 418000, Hunan, China.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Feb;397(2):959-968. doi: 10.1007/s00210-023-02653-9. Epub 2023 Aug 7.
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.
网络药理学和生物信息学用于从铁死亡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。从 FerrDb 中获取铁死亡相关靶点。从 TCMSP、Pharmmappe、SwissTargetPrediction 和 Targetnet 数据库中检索葛根素作用靶点，并补充 PubMed。使用 GEO 数据库中的“骨关节炎”作为搜索词，获取 GSE12021、GSE55235 和 GSE82107 的基因表达谱，对骨关节炎进行差异表达基因筛选分析。使用 Venn 图获取葛根素、铁死亡和骨关节炎的交集靶点。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。在体外实验中测试葛根素对人炎症关节软骨细胞活力以及 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，葛根素维持血脑屏障，调节肽丝氨酸磷酸化，具有抗炎作用。KEGG 分析表明，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 等信号通路。葛根素在分子对接中与 PLIN2、PTGS2、VEGFA 和 IL6 靶点紧密结合。在体外，葛根素预防骨关节炎。网络药理学和生物信息学解释了葛根素多靶点、多途径治疗 OA 的机制，可能与铁死亡有关，并证实了其抗炎作用。
