Acacia Honey Exerts Anti-Inflammatory Activity through Inhibition of NF-κB and MAPK/ATF2 Signaling Pathway in LPS-Stimulated RAW264.7 Cells

Acacia Honey Exerts Anti-Inflammatory Activity through Inhibition of NF-κB and MAPK/ATF2 Signaling Pathway in LPS-Stimulated RAW264.7 Cells

In this study, we evaluated the anti-inflammatory effect of extracts of leaves (ST-L) and branches (ST-B) from Sageretia theezans in LPS-stimulated RAW264.7 cells. ST-L and ST-B significantly inhibited the production of the pro-inflammatory mediators such as NO, iNOS, COX-2, <TEX>$IL-1{\beta}$</TEX> and IL-6 in LPS-stimulated RAW264.7 cells. ST-L and ST-B blocked LPS-induced degradation of <TEX>$I{\kappa}B-{\alpha}$</TEX> and nuclear accumulation of p65, which resulted to the inhibition of <TEX>$NF-{\kappa}B$</TEX> activation in RAW264.7 cells. ST-L and ST-B also attenuated the phosphorylation of ERK1/2, p38 and JNK in LPS-stimulated RAW264.7 cells. In addition, ST-L and ST-B increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of ST-L and ST-B against LPS-induced NO production in RAW264.7 cells. Inhibition of p38 activation and ROS elimination attenuated HO-1 expression by ST-L and ST-B, and ROS elimination inhibited p38 activation induced by ST-L and ST-B. ST-L and ST-B dramatically induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 activation and ROS elimination. Collectively, our results suggest that ST-L and ST-B exerts potential anti-inflammatory activity by suppressing <TEX>$NF-{\kappa}B$</TEX> and MAPK signaling activation, and activating HO-1 expression through the nuclear accumulation of Nrf2 via ROS-dependent p38 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.