Inhibitory effect of Artemisia capillaris extract on cytokine-induced nitric oxide formation and cytotoxicity of RINm5F cells

Abstract

Cytokines produced by immune cells infiltrating pancreatic islets are important mediators of beta-cell destruction in insulin-dependent diabetes mellitus. Cytokines stimulate an inducible form of nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, leading to insulin insufficiency. In the present study, the effects of Artemisia capillaris extract (ACE) on cytokine-induced beta-cell damage were examined. Treatment of RINm5F (RIN) rat insulinoma cells with interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma) induced cell damage. ACE completely protected IL-1 beta and IFN-gamma-mediated cytotoxicity in a concentration-dependent manner. Incubation with ACE resulted in a significant reduction in IL-1 beta and IFN-gamma-induced NO production, a finding that correlated well with reduced levels of the iNOS mRNA and protein. The molecular mechanism by which ACE inhibited iNOS gene expression appeared to involve the inhibition of NF-kappa B activation. The IL-1 beta and IFN-gamma-stimulated RIN cells showed increases in NF-kappa B binding activity and p65 subunit levels in the nucleus, and I kappa B alpha degradation in cytosol compared to unstimulated cells. Furthermore, ACE restored the cytokine-induced inhibition of insulin release from isolated islets. These results suggest that ACE protects beta-cells by suppressing NF-kappa B activation.