Wogonin inhibits the migration and invasion of fibroblast-like synoviocytes by targeting PI3K/AKT/NF- κ B pathway in rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is currently an autoimmune inflammatory disease with an unclear pathogenesis. Fibroblast-like synoviocytes (FLSs) have tumor-like properties, and their activation and secretion of pro-inflammatory factors are important factors in joint destruction. Wogonin (5,7-dihydroxy-8-methoxyflavone), a natural flavonoid isolated from Scutellaria baicalensis root, has been shown to have significant antiinflammatory, anti-oxidative stress, and anti-tumor effects in a variety of diseases. However, the role of wogonin in RA has not yet been demonstrated. Purpose: To investigate the inhibitory effect of wogonin on the invasive behavior of fibroblast-like synoviocytes and to explore the mechanism of action of wogonin in RA. Methods: CCK-8, EdU, cell migration and invasion, immunofluorescence staining, RT-qPCR, and protein blot analysis were used to study the inhibitory effects of wogonin on migration, invasion, and pro-inflammatory cytokine overexpression in the immortalized rheumatoid synovial cell line MH7A. The therapeutic effects of wogonin were validated in vivo using arthritis scores and histopathological evaluation of collagen-induced arthritis mice. Results: Wogonin inhibited the migration and invasion of MH7A cells, reduced the production of TNF-alpha, IL-1 beta, IL6, MMP-3 and MMP-9, and increased the expression of IL-10. Moreover, wogonin also inhibited the myofibrillar differentiation of MH7A cells, increased the expression of E-cadherin (E-Cad) and decreased the expression of alpha-smooth muscle actin (alpha-SMA). In addition, wogonin treatment effectively ameliorated joint destruction in CIA mice. Further molecular mechanism studies showed that wogonin treatment significantly inhibited the activation of PI3K/AKT/NF-kappa B signaling pathway in TNF-alpha-induced arthritic FLSs. Conclusion: Wogonin effectively inhibits migration, invasion and pro-inflammatory cytokine production of RA fibroblast-like synoviocytes through the PI3K/AKT/NF-kappa B pathway, and thus wogonin, as a natural flavonoid, has great potential for treating RA.