Apigenin inhibits release of inflammatory mediators by blocking the NF-κB activation pathways in the HMC-1 cells

Apigenin is a plant flavonoid and a pharmacologically active agent that has been isolated from several plant species. However, the molecular mechanism of apigenin-mediated immune modulation has not been fully understood. One of the possible mechanisms of its protective effects is the down-regulation of inflammatory responses. In this study, we used cells from the human mast cell line (HMC-1) to investigate this effect. Apigenin significantly inhibits the inductive effect of phorbol 12-myristate 13-acetate (PMA) plus A23187 on the production of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-8, IL-6, and granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, apigenin attenuated the cyclooxygenase (COX)-2 expression and intracellular Ca2+ level. In activated HMC-1 cells, apigenin inhibited the PMA plus A23187-induced activation of nuclear factor (NF)-kappa B, I kappa B degradation, and luciferase activity. Furthermore, apigenin suppressed the expression of TNF-alpha, IL-8, IL-6, GM-CSF, and COX-2 by decreasing the intracellular Ca2+ level and inhibiting NF-kappa B activation. These results indicate that apigenin has a potential regulatory effect on inflammatory reactions that are mediated by mast cells.