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

Exp Mol Med. 2007 Apr 30;39(2):149-59. doi: 10.1038/emm.2007.17.

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-kappaB activation. The IL-1beta and IFN-gamma-stimulated RIN cells showed increases in NF-kappaB binding activity and p65 subunit levels in nucleus, and IkappaB alpha 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.

Publication types

  • Research Support, Non-U.S. Gov't

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 / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / cytology*
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / enzymology
  • Interferon-gamma / pharmacology*
  • Interleukin-1beta / pharmacology*
  • Male
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Protein Transport / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Coptidis rhizoma extract
  • Drugs, Chinese Herbal
  • I-kappa B Proteins
  • Insulin
  • Interleukin-1beta
  • NF-kappa B
  • Nfkbia protein, rat
  • RNA, Messenger
  • NF-KappaB Inhibitor alpha
  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase Type II
  • Glucose