Effect of Astragalus polysaccharides on expression of TNF-α, IL-1ß and NFATc4 in a rat model of experimental colitis.

ABSTRACT

AIM: Astragalus membranaceus is a Chinese medicinal herb and has been shown to improve hapten-induced experimental colitis. One of its major components is polysaccharides. We investigated the effect of Astragalus polysaccharides (APS) on expression of TNF-α, IL-1ß and NFATc4 in a rat model of experimental colitis. METHODS: The experimental colitis model was induced by TNBS. Forty five rats were divided into five groups (n=9) Normal control group, receiving ethanol vehicle with no TNBS during induction and IP saline injection during treatment; TNBS colitis model group (TNBS+IP saline), receiving only IP saline vehicle treatment; APS low dose group (TNBS+L-APS), receiving APS 100mg/kg; APS high dose group (TNBS+H-APS), receiving APS 200mg/kg; and positive control group (TNBS+Dexm), receiving dexamethasone 0.3mg/kg. The clinical features, macroscopic and microscopic scores were assessed. The expressions of TNF-α, IL-1ß and NFATc4 were measured by real-time PCR and ELISA assays. RESULTS: Compared to normal control rats, TNBS+IP saline had significant weight loss, increased macroscopic and microscopic scores, higher disease activity index (DAI) up-regulation of TNF-α, IL-1ß and NFATc4 mRNA expression and up-regulation of TNF-α and IL-1ß protein expression. Compared to TNBS+IP saline, treatment with APS or dexamethasone significantly reduced DAI, partially but significantly prevented TNBS colitis-induced weight loss and improved both macroscopic and microscopic scores; high dose APS or dexamethasone significantly down-regulated TNF-α and IL-1ß expressions (both mRNA and protein) and up-regulated NFATc4 mRNA and protein expression. The effect of high dose APS and dexamethasone is comparable. CONCLUSIONS: APS significantly improved experimental TNBS-induced colitis in rats through regulation of TNF-α, IL-1ß and NFATc4 expression.