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

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-alpha, IL-1 beta 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 100 mg/kg; APS high dose group (TNBS + H-APS), receiving APS 200 mg/kg; and positive control group (TNBS + Dexm), receiving dexamethasone 0.3 mg/kg. The clinical features, macroscopic and microscopic scores were assessed. The expressions of TNF-alpha, IL-1 beta 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-alpha, IL-1 beta and NFATc4 mRNA expression and up-regulation of TNF-alpha and IL-1 beta 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-alpha, and IL-1 beta 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-alpha, IL-1 beta and NFATc4 expression. (C) 2014 The Authors. Published by Elsevier Ltd.