Brusatol inhibits the response of cultured beta-cells to pro-inflammatory cytokines in vitro

Biochem Biophys Res Commun. 2015 May 8;460(3):868-72. doi: 10.1016/j.bbrc.2015.03.124. Epub 2015 Mar 28.

Abstract

Brusatol is a natural terpenoid that is capable of inducing a variety of biological effects. We presently report that this substance dramatically improves beta-cell survival when exposed to pro-inflammatory cytokines (IL-1β and IFNγ) in vitro. This was observed in insulin producing rat (RIN-5AH), mouse (βTC6) and human (EndoC-βH1) beta-cell lines. Brusatol prevented beta-cell oxidative stress in response to cytokines and counteracted induction of iNOS on the protein level. Brusatol, however, block neither the cytokine-induced increase of iNOS mRNA, nor NF-κB activation, suggesting that inhibition of iNOS protein expression relies on posttranscriptional mechanism. This indicates that brusatol acts via a novel protective pathway, which may represent a more promising way of improving beta-cell function and survival.

Keywords: Beta-cells; Brusatol; Cytokines; Oxidative stress; iNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Cytokines / physiology*
  • DNA Primers
  • In Vitro Techniques
  • Inflammation Mediators / physiology*
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / physiology
  • Mice
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress
  • Quassins / pharmacology*
  • Rats
  • Real-Time Polymerase Chain Reaction

Substances

  • Cytokines
  • DNA Primers
  • Inflammation Mediators
  • Quassins
  • brusatol
  • Nitric Oxide Synthase Type II