Kalopanaxsaponin A ameliorates experimental colitis in mice by inhibiting IRAK-1 activation in the NF-κB and MAPK pathways.

摘要: BACKGROUND AND PURPOSE Kalopanaxsaponin A, a triterpenoid saponin isolated from Kalopanax pictus (family Araliaceae), potently inhibited nuclear factor-kappa B (NF-κB) activation in lipopolysaccharide (LPS)-stimulated peritoneal macrophages during screening programme for anti-colitis agents natural products. Its anti-inflammatory mechanism remains unknown. Therefore, we investigated its effects (LPS)- or peptidoglycan-stimulated murine and trinitrobenzene sulphonic acid (TNBS)-induced colitic mice. EXPERIMENTAL APPROACH Peritoneal male ICR mice were stimulated with LPS peptidoglycan vitro treated kalopanaxsaponin A. Colitis was induced vivo by intrarectal administration of TNBS mice. Mice daily sulphasalazine phosphate-buffered saline. Inflammatory markers, cytokines, enzymes transcription factors measured ELISA, immunoblot, flow cytometry immunofluorescent confocal microscopy. KEY RESULTS A the expression pro-inflammatory interleukin (IL)-1β, tumour necrosis factor (TNF)-α IL-6, LPS, but not that TNF-α, macrophages. However, it increased cytokine IL-10. IL-1 receptor-associated kinase (IRAK)-1, inhibitor κB kinase-β, NF-κB mitogen-activated protein kinases (extracellular signal-regulated kinase, c-Jun NH2-terminal p-38), LPS/Toll-like receptor-4 interaction IRAK-4 affected. Oral (10 20 mg·kg−1) improved clinical parameters histology vivo. suppressing IRAK-1 activation. CONCLUSIONS IMPLICATIONS may improve inflammatory diseases, such as colitis, inhibiting activation.