Astragalin Inhibits Nuclear Factor-κB Signaling in Human Colonic Epithelial Cells and Attenuates Experimental Colitis in Mice
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Background/Aims: Astragalin (kaempferol-3-O-β-D-glucoside) is a flavonoid isolated from the leaves of persimmon or Rosa agrestis. Astragalin exhibits various anti-inflammatory properties; however, little is known about its therapeutic potential for inflammatory bowel disease (IBD). This study aims to investigate the anti-inflammatory effect of astragalin via blockade of the nuclear factor κB (NF-κB) signaling pathway in human colonic epithelial cells and a murine colitis model. Methods: HCT-116 and HT-29 human colonic epithelial cells were pretreated with astragalin and stimulated with tumor necrosis factor-α (TNF-α). Cell viability was assessed by the MTS assay. Real-time reverse transcription polymerase chain reaction was used to analyze the messenger RNA expression of the inflammatory cytokines interleukin (IL)-6 and IL-8. The effect of astragalin on the NF-κB pathway was evaluated by Western blot analysis of inhibitor of NF-κB alpha (IκBα) phosphorylation/degradation and by electrophoretic mobility shift assay. Dextran sulfate sodium (DSS)-induced acute murine colitis model was used for in vivo experiments. Results: Astragalin strongly suppressed the expression of proinflammatory cytokines in human colonic epithelial cells in a dose-dependent manner. Western blot analysis showed that astragalin inhibited IκBα phosphorylation/degradation. Additionally, astragalin reduced the DNA binding activity of NF-κB. Astragalin alleviated colon shortening and improved the pathologic scores in DSSinduced acute murine colitis model. Furthermore, astragalin reduced the level of phosphorylated IκBα and decreased the production of the inflammatory cytokines IL-6, IL-8, and TNF-α in the DSS-treated colon mucosa. Conclusions: Astragalin exerted an anti-inflammatory effect through NF-κB pathway inhibition and attenuated murine colitis. Astragalin is thus a potential therapeutic agent for IBD.
Abstract
Background/Aims: Astragalin (kaempferol-3-O-β-D-glucoside) is a flavonoid isolated from the leaves of persimmon or Rosa agrestis. Astragalin exhibits various anti-inflammatory properties; however, little is known about its therapeutic potential for inflammatory bowel disease (IBD). This study aims to investigate the anti-inflammatory effect of astragalin via blockade of the nuclear factor κB (NF-κB) signaling pathway in human colonic epithelial cells and a murine colitis model. Methods: HCT-116 and HT-29 human colonic epithelial cells were pretreated with astragalin and stimulated with tumor necrosis factor-α (TNF-α). Cell viability was assessed by the MTS assay. Real-time reverse transcription polymerase chain reaction was used to analyze the messenger RNA expression of the inflammatory cytokines interleukin (IL)-6 and IL-8. The effect of astragalin on the NF-κB pathway was evaluated by Western blot analysis of inhibitor of NF-κB alpha (IκBα) phosphorylation/degradation and by electrophoretic mobility shift assay. Dextran sulfate sodium (DSS)-induced acute murine colitis model was used for in vivo experiments. Results: Astragalin strongly suppressed the expression of proinflammatory cytokines in human colonic epithelial cells in a dose-dependent manner. Western blot analysis showed that astragalin inhibited IκBα phosphorylation/degradation. Additionally, astragalin reduced the DNA binding activity of NF-κB. Astragalin alleviated colon shortening and improved the pathologic scores in DSSinduced acute murine colitis model. Furthermore, astragalin reduced the level of phosphorylated IκBα and decreased the production of the inflammatory cytokines IL-6, IL-8, and TNF-α in the DSS-treated colon mucosa. Conclusions: Astragalin exerted an anti-inflammatory effect through NF-κB pathway inhibition and attenuated murine colitis. Astragalin is thus a potential therapeutic agent for IBD.
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