Avicularin Inhibits Lipopolysaccharide-Induced Inflammatory Response by Suppressing ERK Phosphorylation in RAW 264.7 Macrophages

Avicularin, quercetin-3-alpha-L-arabinofuranoside, has been reported to possess diverse pharmacological properties such as anti-inflammatory and anti-infectious effects. However, the underlying mechanism by which avicularin exerts its anti-inflammatory activity has not been clearly demonstrated. This study aimed to elucidate the anti-inflammatory mechanism of avicularin in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. Avicularin significantly inhibited LPS-induced excessive production of pro-inflammatory mediators such as nitric oxide (NO) and PGE(2) and the protein levels of iNOS and COX-2, which are responsible for the production of NO and PGE(2), respectively. Avicularin also suppressed LPS-induced overproduction of pro-inflammatory cytokine IL-1 beta. Furthermore, avicularin significantly suppressed LPS-induced degradation of I kappa B, which retains NF-kappa B in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-kappa B in the nucleus. To understand the underlying signaling mechanism of anti-inflammatory activity of avicularin, involvement of multiple kinases was examined. Avicularin significantly attenuated LPS-induced activation of ERK signaling pathway in a concentration-dependent manner. Taken together, the present study clearly demonstrates that avicularin exhibits anti-inflammatory activity through the suppression of ERK signaling pathway in LPS-stimulated RAW 264.7 macrophage cells.