Carvacrol Suppresses Inflammatory Responses in Rheumatoid Arthritis Fibroblast‐like Synoviocytes

Background Fibroblast-like synoviocytes (FLSs) play an essential role in the chronic inflammatory process of rheumatoid arthritis (RA). Carvacrol is a natural monoterpenic phenol that retains significant anti-inflammatory activity. However, the effect of carvacrol on inflammatory response in RA-FLSs has not yet been reported. The present study aimed to investigate the role of carvacrol in lipopolysaccharides (LPS)-induced inflammatory response in human RA-FLSs. Methods Cell viability and proliferation were measured by MTT and Cell Counting Kit-8 assays, respectively. The migration was detected by transwell assay. The production of inflammatory cytokines and matrix metalloproteinases (MMPs) were analyzed by enzyme-linked immunosorbent assay. The expressions of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), NF-kappa B, p38, p-p38, ERK1/2, p-ERK1/2, c-Jun N-terminal kinase (JNK), and p-JNK were detected by Western blot analysis. Results Carvacrol-inhibited LPS-induced cell proliferation and migration of RA-FLSs. The production of inflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)- 6, and IL-8, was reduced by carvacrol in LPS-induced RA-FLSs. Meanwhile, the induction of MMPs, including MMP-1, MMP-3, and MMP-13, caused by LPS stimulation was inhibited by carvacrol in RA-FLSs. Furthermore, carvacrol prevented LPS-induced activation of the TLR4/MyD88/NF-kappa B, p38, and ERK1/2 pathways in RA-FLSs. Conclusions Carvacrol-mitigated LPS-induced cell proliferation, migration, and inflammation in RA-FLSs. The TLR4/MyD88/NF-kappa B, p38 and ERK1/2 pathways might be involved in the protective effect of carvacrol.