6-Gingerol inhibits Vibrio cholerae-induced proinflammatory cytokines in intestinal epithelial cells via modulation of NF-κB

Abstract

Context The effect of 6-gingerol (6G), the bioactive component of Zingiber officinale Roscoe (Zingiberaceae), in the reduction of Vibrio cholerae (Vibrionaceae)-induced inflammation has not yet been reported. Objective This study reports the anti-inflammatory effect of 6-gingerol against V. cholerae-induced inflammation in intestinal epithelial (Int 407) cells. Materials and methods Cell viability assay was performed to determine the working concentration of 6G. Elisa and RT-PCR were performed with Int 407 cells treated with 50 mM 6G and 100 multiplicity of infection (MOI) V. cholerae for 0, 2, 3, 3.5, 6 and 8 h to determine the concentration of IL-8, IL-6, IL-1a and IL-1b in both protein and RNA levels. Furthermore, the effect of 50 mM 6G on upstream MAP-kinases and NF-jB signalling pathways was evaluated at 0, 10, 15, 30, 60 and 90 min. Results The effective dose (ED 50 ) value of 6G was found to be 50 mM as determined by cell viability assay. Pre-treatment with 50 mM 6G reduced V. cholerae infection-triggered levels of IL-8, IL-6, IL-1a and IL-1b by 3.2-fold in the protein level and two-fold in the RNA level at 3.5 h. The levels of MAPkinases signalling molecules like p38 and ERK1/2 were also reduced by two-and three-fold, respectively, after 30 min of treatment. Additionally, there was an increase in phosphorylated IkBa and down-regulation of p65 resulting in down-regulation of NF-jB pathway. Conclusion Our results showed that 6G could modulate the anti-inflammatory responses triggered by V. cholerae-induced infection in intestinal epithelial cells by modulating NF-jB pathway.ARTICLE HISTORY

Effects of shinbuto and ninjinto on prostaglandin E2 production in lipopolysaccharide-treated human gingival fibroblasts

“…6-Gingerol and 6-shogaol suppressed COX-2 expression in mouse macrophage RAW264.7 cells (Pan et al, 2008) and primary rat astrocytes (Shim et al, 2011). 6-Gingerol reduceed the production of IL-1α, IL-1β , IL-6, and IL-8 in intestinal epithelial cells (Saha et al, 2016). However, shinbuto and ninjinto, which contain shokyo and kankyo, respectively, increased LPS-induced IL-6 and IL-8 production by HGFs (Fig.…”

Effects of shinbuto and ninjinto on prostaglandin E2production in lipopolysaccharide-treated human gingival fibroblasts

“…Both the expression of COX-2, and the production of IL-6 and IL-8 are widely known to be regulated by NF- κ B. Ginger and its components gingerol and shogaol have been reported to suppress NF- κ B activation, and to reduce COX-2 expression and the production of IL-6 and IL-8. For example, ginger suppressed NF- κ B activation in ovarian cancer cells ( Rhode et al, 2007 ), and 6-gingerol suppressed NF- κ B activation in mouse macrophage RAW264.7 cells ( Pan et al, 2008 ), TPA-treated mouse skin in vivo ( Kim et al, 2005 ), and in intestinal epithelial cells ( Saha et al, 2016 ). Similarly, 6-shogaol suppressed NF- κ B activation in mouse macrophage RAW264.7 cells ( Pan et al, 2008 ) and microglia cells ( Ha et al, 2012 ).…”

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“…6-Gingerol and 6-shogaol suppressed COX-2 expression in mouse macrophage RAW264.7 cells (Pan et al, 2008) and primary rat astrocytes (Shim et al, 2011). 6-Gingerol reduceed the production of IL-1α, IL-1β , IL-6, and IL-8 in intestinal epithelial cells (Saha et al, 2016). However, shinbuto and ninjinto, which contain shokyo and kankyo, respectively, increased LPS-induced IL-6 and IL-8 production by HGFs (Fig.…”

“…Ginger and its components gingerol and shogaol have been reported to suppress NF-κB activation, and to reduce COX-2 expression and the production of IL-6 and IL-8. For example, ginger suppressed NF-κB activation in ovarian cancer cells (Rhode et al, 2007), and 6-gingerol suppressed NF-κB activation in mouse macrophage RAW264.7 cells (Pan et al, 2008), TPA-treated mouse skin in vivo (Kim et al, 2005), and in intestinal epithelial cells (Saha et al, 2016). Similarly, 6-shogaol suppressed NF-κB activation in mouse macrophage RAW264.7 cells (Pan et al, 2008) and microglia cells (Ha et al, 2012).…”