Effects of isoflavone derivatives on the production of inflammatory cytokines by synovial cells.

The present study investigated the effects of isoflavone derivatives (daidzein, genistein and glycitein) on the production of inflammatory cytokines (IL-6 and IL-8) by IL-1β-stimulated synovial cells. Synovial MH7A cells were stimulated with IL-1β in the absence or presence of isoflavone derivatives, and IL-6 and IL-8 production was measured by ELISA. The results of the present study indicated that daidzein significantly inhibited the production of IL-6, but not IL-8. Conversely, neither genistein nor glycitein exerted any inhibitory effects on the production of IL-6 or IL-8 by IL-1β-stimulated synovial cells. To elucidate the molecular mechanisms underlying the daidzein-mediated inhibition of IL-6 production, the present study examined the effects of daidzein on the phosphorylation (activation) of NF-κB p65, ERK1/2 and p38 MAPK. Daidzein significantly inhibited the phosphorylation of NF-κB p65 and ERK1/2, but not p38 MAPK in IL-1β-stimulated MH7A cells. The present study revealed that among the isoflavone derivatives examined (daidzein, genistein and glycitein), daidzein inhibited the production of IL-6, but not IL-8, by IL-1β-stimulated synovial MH7A cells via the suppression of NF-κB p65 and ERK1/2 activation. Collectively, these results suggested that daidzein may have potential as a therapeutic agent for the treatment of arthritic disorders through its anti-inflammatory effects via the inhibition of IL-6 production.