Radix asati extract protects pancreatic β cells against cytokine-induced toxicity:: Implication of the NF-κB-iNOS signaling cascade

Abstract

In this study, we assessed the preventive effects of Radix asari extract (RAE) against cytokine-induced beta-cell destruction. Cytokines secreted by immune cells that have infiltrated pancreatic islets are crucial mediators of beta-cell destruction in insulin-dependent diabetes mellitus. Treatment of RINm5F (RIN) cells with interleukin (IL)-1 beta and interferon (IFN)-gamma resulted in a reduction of cell viability and proliferation. However, treatment of RIN cells with RAE protected the IL-1 beta and IFN-gamma-mediated viability and proliferation reduction in a concentration-dependent manner. Incubation with RAE also resulted in significant suppression of IL-1 beta and IFN-gamma-induced nitric oxide (NO) production, and this reduction was correlated with reduced levels of mRNA and protein associated with the inducible form of NO synthase (iNOS). The molecular mechanism by which RAE inhibited iNOS gene expression appeared to involve the inhibition of NF-kappa B activation as a result of RAE's suppression of IL-1 beta and IFN-gamma-induced I kappa B alpha degradation. The protective effects of RAE were verified via the observation of reduced NO generation and iNOS expression, as well as the observation of normal insulin- secretion responses to glucose in IL-1 beta and IFN-gamma-treated rat islets. These results suggest that RAE protects 6 cells from cytokine toxicity by suppression of NF-kappa B activation.