Astragalin Inhibits Nuclear Factor-κB Signaling in Human Colonic Epithelial Cells and Attenuates Experimental Colitis in Mice

Background/Aims: Astragalin (kaempferol-3-beta-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 kappa B (NF-kappa B) 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-alpha (INF-alpha). 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-kappa B pathway was evaluated by Western blot analysis of inhibitor of NF-kappa B alpha (I kappa B alpha) 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 I kappa B alpha phosphorylation/degradation. Additionally, astragalin reduced the DNA binding activity of NE-kappa B. Astragalin alleviated colon shortening and improved the pathologic scores in DSSinduced acute murine colitis model. Furthermore, astragalin reduced the level of phosphorylated I kappa B alpha and decreased the production of the inflammatory cytokines IL-6, IL-8, and INF-alpha in the DSS-treated colon mucosa. Conclusions: Astragalin exerted an anti-inflammatory effect through NE-kappa B pathway inhibition and attenuated murine colitis. Astragalin is thus a potential therapeutic agent for IBD.

Automated summary

Astragalin demonstrated anti-inflammatory effects by inhibiting the NF-κB signaling pathway in human colonic epithelial cells and a murine colitis model. It suppressed the expression of proinflammatory cytokines and improved colon inflammation in mice, suggesting its potential as a therapeutic agent for inflammatory bowel disease.