Exp Mol Med.  2007 Apr;39(2):149-159.

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

• Kim EK
• Kwon KB
• Han MJ
• Song MY
• Lee JH
• Lv N
• Ka SO
• Yeom SR
• Kwon YD
• Ryu DG
• Kim KS
• Park JW
• Park R
• Park BH

Abstract

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 beta-cell death was assessed. Cytokines generated by immune cells infiltrating pancreatic islets are crucial mediators of beta-cell destruction in insulin-dependent diabetes mellitus. The treatment of RIN cells with IL-1beta and IFN-gamma resulted in a reduction of cell viability. CRE completely protected IL-1beta and IFN-gamma-mediated cell death in a concentration-dependent manner. Incubation with CRE induced a significant suppression of IL-1beta and IFN-gamma-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-kappa B activation. The IL-1beta and IFN-gamma-stimulated RIN cells showed increases in NF-kappa B binding activity and p65 subunit levels in nucleus, and IkappaBalpha 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-1beta and IFN-gamma-treated islets.

Keyword

cell death; Coptidis rhizoma extract; cytokines; drugs, Chinese herbal; insulin secreting cells; NF-kappa B; nitric oxide

MeSH Terms

Animals
Cell Death/drug effects
Cell Line
Cell Nucleus/metabolism
Cell Survival/drug effects
Drugs, Chinese Herbal/*pharmacology
Gene Expression Regulation, Enzymologic/drug effects
Glucose/pharmacology
I-kappa B Proteins/metabolism
Insulin/secretion
Insulin-Secreting Cells/*cytology/*drug effects/enzymology
Interferon-gamma/*pharmacology
Interleukin-1beta/*pharmacology
Male
NF-kappa B/*metabolism
Nitric Oxide/biosynthesis
Nitric Oxide Synthase Type II/genetics/metabolism
Protein Transport/drug effects
RNA, Messenger/genetics/metabolism
Rats
Rats, Sprague-Dawley