Sauchinone protects pancreatic β cells against cytokine-mediated toxicity

Abstract

Sauchinone has been shown to exert potent hepatoprotective, anti-inflammatory and inhibitory effects on bone resorption. In this study, we investigated the effect of sauchinone on IL-1 beta (5 ng/ml) and IFN-gamma (100 U/mI)-induced beta-cell damage. Pre-treatment with sauchinone increased the viability of cytokine-treated RINm5F cells at concentrations of 20-40 mu M. Sauchinone prevented nitric oxide (NO) production, and this effect was correlated with reduced levels of protein expression of the inducible form of NO synthase (iNOS). The molecular mechanism by which sauchinone inhibits iNOS gene expression appeared to involve the inhibition of NF-kappa B activation. Moreover, pancreatic beta-cells treated with cytokines upregulated the phosphorylation of STAT-1, STAT-3 and STAT-5, however, pre-treatment with sauchinone attenuated these effects. Additionally, in a second set of experiments in which rat islets were used, the protective effects of sauchinone in rat islets were essentially the same as those observed when RINm5F cells were used. Sauchinone prevented cytokine-induced NO production, iNOS expression, JAK/STAT activation, and NF-kappa B activation and inhibition of glucose-stimulated insulin secretion (GSIS). Collectively, these results suggest that sauchinone can be used for the prevention of functional beta-cell damage. (C) 2010 Elsevier Ltd. All rights reserved.