Fructus Xanthii extract protects against cytokine-induced damage in pancreatic β-cells through suppression of NF-κB activation
- Authors: Mi-Young Song, Eun-Kyung Kim, Heon-Jae Lee, Jin-Woo Park, Do-Gon Ryu, Kang-Beom Kwon, Byung-Hyun Park
Published online on: Wednesday, April 1, 2009
- Pages: 547-553
- DOI: 10.3892/ijmm_00000163
Cytokines released by infiltrating inflammatory cells around the pancreatic islets are involved in the pathogenesis of type 1 diabetes. Interleukin (IL)-1β and interferon (IFN)-γ are the primary cytokines responsible for stimulation of inducible nitric oxide synthase (iNOS) expression and nitric oxide overproduction, which leads to β-cell damage. In addition, nuclear factor-κB (NF-κB) plays a crucial role in the activation of this pathway. Therefore, suppression of the cytokine-NF-κB pathway is considered an effective therapeutic strategy for preventing inflammatory reactions in pancreatic β-cells. In this study, the effects of Fructus Xanthii extract (FXE) on IL-1β and IFN-γ-induced β-cell damage were examined. Treatment of RINm5F cells with IL-1β and IFN-γ reduced cell viability, however, FXE completely protected cells from IL-1β and IFN-γ-mediated reduction in viability in a concentration-dependent manner. In addition, incubation with FXE resulted in a significant suppression of IL-1β and IFN-γ-induced nitric oxide (NO) production, which correlated with the reduced levels of the inducible form of iNOS mRNA and protein observed. The IL-1β and IFN-γ-stimulated RIN cells showed increases in NF-κB binding activity and p50 subunit levels in the nucleus, as well as increased IκBα degradation in cytosol when compared to unstimulated cells, which indicates that the mechanism by which FXE inhibited the iNOS gene involves inhibition of NF-κB activation. Furthermore, a protective effect of FXE was demonstrated by reduction in NO generation and iNOS expression, as well as the normal insulin secreting responses to glucose observed in IL-1β and IFN-γ-treated islets.