Exploring the mechanism of triptolide inhibiting the motility of fibroblast-like synoviocytes in rheumatoid arthritis via RhoA/Rho-associated kinase axis, based on network pharmacology, molecular docking and molecular dynamics simulations

作者：Jiacheng Shen, Yuxuan Fang, Nan Xu, Hongyi Chen, Miao Zhu, Dan Li, Zewen Chu, Masataka Sunagawa, Yanqing Liu, Haibo Wang, Guoqing Li · 发表于：Frontiers in Pharmacology · 年份：2025 · DOI：10.3389/fphar.2025.1545514 · 被引用次数：11 · 研究领域：Natural Compounds in Disease Treatment、Rheumatoid Arthritis Research and Therapies、Autoimmune and Inflammatory Disorders Research

Background and objective Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by the hyperproliferation and invasive behavior of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), which contributes to the degradation of articular cartilage and bone. Inhibition of RA-FLS proliferation, migration and invasion has become an important therapeutic strategy for RA. Triptolide (TPL), an epoxy diterpene lactone compound from the traditional Chinese medicine Tripterygium wilfordii Hook. f. , has significant immunosuppressive and anti-inflammatory effects. However, the specific mechanisms of TPL-regulated effects on RA-FLS cytoskeleton and inhibition of invasive metastasis are not yet fully explored. The aim of this study was to investigate TPL-regulated effects on RA-FLS skeleton and reveal the specific mechanism of TPL-inhibition of RA-FLS migration and invasion. Materials and methods In vitro experiments were performed using RA-FLS cell line. Cell motility was evaluated by wound healing assay and Transwell assay as well as high content cell imaging system. Cytoskeletal remodeling was observed by cytoskeletal immunofluorescence staining and transmission electron microscopy (TEM). Network pharmacology predicted the targets of Triptolide. RhoA/Rho-associated kinase signaling pathway was detected by quantitative real-time PCR and Western blotting. Molecular docking and molecular dynamics simulations were used to validate the interaction of Triptolide with Rho...