Chemico-biological interactions
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Chem. Biol. Interact. · Apr 2014
Anti-inflammatory effects of genistein via suppression of the toll-like receptor 4-mediated signaling pathway in lipopolysaccharide-stimulated BV2 microglia.
Genistein, a principal soy isoflavone, has received considerable attention as a protein kinase inhibitor. Although some studies have demonstrated that genistein possesses anti-inflammatory effects, the molecular mechanisms of genistein-mediated anti-inflammatory potential are unclear in microglial cells. In this study, we determined whether genistein attenuates pro-inflammatory responses in lipopolysaccharide (LPS)-stimulated BV2 microglia and attempted to establish the possible mechanisms. ⋯ Furthermore, genistein potently suppressed binding of LPS to the microglial cell surface, indicating the antagonistic effect of genistein against toll like receptor 4 (TLR4), and inhibited LPS-induced TLR4 and myeloid differentiation factor 88 expression. In addition, blocking TLR4 signaling using the specific TLR4 signaling inhibitor CLI-095 increased the anti-inflammatory potential of genistein in BV2 microglia. Our data indicate that genistein may attenuate the initiation of intracellular signaling cascades by LPS through inhibiting NF-κB activation by inhibiting the binding of LPS to TLR-4 on microglial cells.