Shentong Zhuyu Decoction Inhibits Inflammatory Response, Migration, and Invasion and Promotes Apoptosis of Rheumatoid Arthritis Fibroblast-like Synoviocytes via the MAPK p38/PPARγ/CTGF Pathway

Abstract

Introduction. The current study is aimed at exploring the effect of Shentong Zhuyu Decoction on the proliferation, migration, invasion, and apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and its underlying molecular mechanism. Materials and Methods. The type II collagen-induced arthritis (CIA) model was established. Subsequently, the RA-FLS were isolated from the CIA rat model and identified by immunohistochemistry. The viability, apoptosis, cell cycle, migration, and invasion of RA-FLS were detected by the cell counting kit 8 (CCK-8) assay, flow cytometry, wound-healing assay, and transwell invasion assay, respectively. The levels of MAPK p38, PPARγ, CTGF, Bcl-2, Bax, caspase-3, IL-1β, MMP-3, CDK4, and cyclin D1 were determined by qRT-PCR and western blotting, respectively. Results. After treatment with Shentong Zhuyu Decoction medicated serum, the OD570 value, migrative and invasive abilities, and the secretion of IL-1β, MMP-3 were remarkably decreased in RA-FLS, while the apoptosis rate was increased. Further, results showed that Shentong Zhuyu Decoction inhibited the transition from the G1 phase to S phase. Additionally, Shentong Zhuyu Decoction significantly inhibited the expression of Bcl-2, CDK4, cyclin D1, MAPK p-p38, and CTGF, whereas elevated the levels of Bax, caspase-3, and PPARγ. Importantly, the effects of Shentong Zhuyu Decoction were consistent with the trends of MAPK P38 inhibitor (SB203580) and PPARγ agonist (GW1929). Conclusions. Shentong Zhuyu Decoction inhibited viability, inflammatory response, migration, invasion, and transition from the G1 phase to S phase and promoted apoptosis of RA-FLS via the MAPK p38/PPARγ/CTGF pathway.