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

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Honey used as conventional medicine has various pharmacological properties. In the honey andanti-inflammatory effect, Gelam honey and Manuka honey has been reported to exert anti-inflammatory activity. However,the anti-inflammatory effect and potential mechanisms of acacia honey (AH) are not well understood. In this study, weinvestigated anti-inflammatory activity and mechanism of action of AH in LPS-stimulated RAW264.7 cells. AH attenuatedNO production through inhibition of iNOS expression in LPS-stimulated RAW264.7 cells. AH also decreased theexpressions of IL-1β, IL-6 and TNF-α as pro-inflammatory cytokines, and MCP-1 expression as a pro-inflammatorychemokine. In the elucidation of the molecular mechanisms, AH decreased LPS-mediated IκB-α degradation andsubsequent nuclear accumulation of p65, which resulted in the inhibition of NF-κB activation in RAW264.7 cells. AHdose-dependently suppressed LPS-mediated phosphorylation of ERK1/2 and p38 in RAW264.7 cells. In addition, AHsignificantly inhibited ATF2 phosphorylation and nuclear accumulation of ATF2 in LPS-stimulated RAW264.7 cells. These results suggest that AH has an anti-inflammatory effect, inhibiting the production of pro-inflammatory mediatorssuch as NO, iNOS, TNF-α, IL-6, IL-1β and MCP-1 via interruption of the NF-κB and MAPK/ATF2 signaling pathways.

Abstract

Honey used as conventional medicine has various pharmacological properties. In the honey andanti-inflammatory effect, Gelam honey and Manuka honey has been reported to exert anti-inflammatory activity. However,the anti-inflammatory effect and potential mechanisms of acacia honey (AH) are not well understood. In this study, weinvestigated anti-inflammatory activity and mechanism of action of AH in LPS-stimulated RAW264.7 cells. AH attenuatedNO production through inhibition of iNOS expression in LPS-stimulated RAW264.7 cells. AH also decreased theexpressions of IL-1β, IL-6 and TNF-α as pro-inflammatory cytokines, and MCP-1 expression as a pro-inflammatorychemokine. In the elucidation of the molecular mechanisms, AH decreased LPS-mediated IκB-α degradation andsubsequent nuclear accumulation of p65, which resulted in the inhibition of NF-κB activation in RAW264.7 cells. AHdose-dependently suppressed LPS-mediated phosphorylation of ERK1/2 and p38 in RAW264.7 cells. In addition, AHsignificantly inhibited ATF2 phosphorylation and nuclear accumulation of ATF2 in LPS-stimulated RAW264.7 cells. These results suggest that AH has an anti-inflammatory effect, inhibiting the production of pro-inflammatory mediatorssuch as NO, iNOS, TNF-α, IL-6, IL-1β and MCP-1 via interruption of the NF-κB and MAPK/ATF2 signaling pathways.

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