Coptidis rhizoma extract protects against cytokine-induced death of pancreatic [beta]-cells through suppression of NF-[kappa] B activation

• Published in: Experimental & molecular medicine 2007-04, Vol.39 (2), p.149
• Main Authors: Kim, Eun-kyung, Kwon, Kang-beom, Han, Mi-jeong, Song, Mi-young, Lee, Ji-hyun, Lv, Na, Ka, Sun-o, Yeom, Seung-ryong, Kwon, Young-dal, Ryu, Do-gon, Kim, Kang-san, Park, Jin-woo, Park, Raekil, Park, Byung-hyun
• Format: Article
• Language: English
• ISSN: 1226-3613; 2092-6413
• DOI: 10.1038/emm.2007.17

We demonstrated previously that Coptidis rhizoma extract (CRE) prevented S-nitroso-N-acetylpenicillamine-induced apoptotic cell death via the inhibition of mitochondrial membrane potential disruption and cytochrome c release in RINm5F (RIN) rat insulinoma cells. In this study, the preventive effects of CRE against cytokine-induced β-cell death was assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of β-cell destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with IL-1β and IFN-γ resulted in a reduction of cell viability. CRE completely protected IL-1β and IFN-γ-mediated cell death in a concentration-dependent manner. Incubation with CRE induced a significant suppression of IL-1β and IFN-γ-induced nitric oxide (NO) production, a finding which correlated well with reduced levels of the iNOS mRNA and protein. The molecular mechanism by which CRE inhibited iNOS gene expression appeared to involve the inhibition of NF-κ B activation. The IL-1β and IFN-γ-stimulated RIN cells showed increases in NF-κ B binding activity and p65 subunit levels in nucleus, and IκBα degradation in cytosol compared to unstimulated cells. Furthermore, the protective effects of CRE were verified via the observation of reduced NO generation and iNOS expression, and normal insulin-secretion responses to glucose in IL-1β and IFN-γ-treated islets.