Diosmetin exhibits anti-proliferative and anti-inflammatory effects on TNF-alpha-stimulated human rheumatoid arthritis fibroblast-like synoviocytes through regulating the Akt and NF-kappa B signaling pathways

摘要

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by inflammation and proliferation of synovial tissues. Diosmetin is a bioflavonoid possessing an anti-inflammatory property. Herein, we aimed to study the effects of diosmetin on the inflammation and proliferation of RA fibroblast-like synoviocytes MH7A cells. MH7A cell proliferation was measured using cell counting kit-8 assay. Cell apoptosis was examined using flow cytometry. The production of inflammatory cytokines including interleukin (IL)-1 beta, IL-6, IL-8, and matrix metalloproteinase-1 (MMP-1) was measured using enzyme-linked immunosorbent assay (ELISA). Results showed that diosmetin inhibited tumor necrosis factor-alpha (TNF-alpha)-induced proliferation increase in MH7A cells in a dose-dependent manner. Diosmetin treatment resulted in an increase in apoptotic rates and a reduction in TNF-alpha-induced production of IL-1 beta, IL-6, IL-8, and MMP-1 in MH7A cells. Furthermore, diosmetin inhibited TNF-alpha-induced activation of protein kinase B (Akt) and nuclear factor-kappa B (NF-kappa B) pathways in MH7A cells. Suppression of Akt or NF-kappa B promoted apoptosis and inhibited TNF-alpha-induced proliferation increase and production of IL-1 beta, IL-6, IL-8, and MMP-1 in MH7A cells, and diosmetin treatment enhanced these effects. Taken together, these findings suggested that diosmetin exhibited anti-proliferative and anti-inflammatory effects via inhibiting the Akt and NF-kappa B pathways in MH7A cells.