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

Abstract

suppresAvicularin, quercetin-3-α-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 PGE2 and the protein levels of iNOS and COX-2, which are responsible for the production of NO and PGE2, respectively. Avicularin also suppressed LPS-induced overproduction of pro-inflammatory cytokine IL-1β. Furthermore, avicularin significantly suppressed LPS-induced degradation of IκB, which retains NF-κB in the cytoplasm, consequently inhibiting the transcription of pro-inflammatory genes by NF-κB 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.

Quercetin-3-O-β-D-Glucuronide Suppresses Lipopolysaccharide-Induced JNK and ERK Phosphorylation in LPS-Challenged RAW264.7 Cells

“…In addition, we recently demonstrated that N - ( p -coumaryol)-tryptamine significantly inhibited LPS-induced inflammatory responses through the suppression of JNK activation in RAW264.7 cells (Vo et al ., 2014). Furthermore, we also observed that that ERK signaling pathway was activated with LPS treatment and its activation and abnormal inflammatory responses were significantly attenuated with avicularin in LPS-challenged RAW264.7 cells (Vo et al ., 2012). No noticeable changes were observed in phosphorylation p38 with QG, indicating that QG exerts its anti-inflammatory action through the selective inhibition of JNK and ERK signaling pathways in RAW264.7 cells.…”

“…Given the previous studies that quercetin and its glycoside derivatives have pharmacological properties such as anticancer, anti-inflammatory, and anti-oxidant actions (Jagtap et al ., 2009; Pocernich et al ., 2011; Vo et al ., 2012; Yang et al ., 2014), the present study demonstrated that QG, a glucuronic acid glycoside of quercetin, possesses anti-inflammatory properties in LPS-induced RAW264.7 macrophage cells. In addition, the underlying mechanism by which QG exert the anti-inflammatory activity has not been clearly demonstrated.…”

“…Activated macrophages initiate bacterial-mediated pro-inflammatory gene transcription, which leads to the phosphorylation of multiple kinases, which subsequently activates various pro-inflammatory transcription factors including NF-κB and AP-1 (O’Connell et al, 1998; Guha and Mackman, 2001). We previously demonstrated that bacterial LPS results in the expression of pro-inflammatory mediators and the increased degradation IκB (Vo et al, 2012). In the present study, quercetin but not QG significantly attenuated LPS-induced extracellular release of pro-inflammatory cytokines such as TNF-α.…”

“…Recently, it has been reported that suppression of JNK activation with aromadendrin and N -(p-coumaryol)-tryptamine significantly attenuates lipopolysaccharide (LPS)-induced inflammatory responses in RAW264.7 cells (Lee et al ., 2013; Vo et al ., 2014). It has been also demonstrated that avicularin significantly suppressed LPS-induced ERK phosphorylation in RAW264.7 cells (Vo et al ., 2012). …”

“…Pharmacological properties of quercetin glycosides have not been extensively examined. Recently, it has been reported that avicularin, quercetin-3-α-L-arabinofuranoside, exerts antioxidant and anti-inflammatory activity (Vo et al ., 2012). Quercetin-3- O - β -D-glucuronide (QG) has been reported to anti-cancer (Yamazaki et al ., 2014), anti-aging (Yang et al ., 2014), and anti-oxidant properties (Messer et al ., 2015).…”