The synergistic protection of EGCG and quercetin against streptozotocin (STZ)-induced NIT-1 pancreatic β cell damage via upregulation of BCL-2 expression by miR-16-5p

J Nutr Biochem. 2021 Oct:96:108748. doi: 10.1016/j.jnutbio.2021.108748. Epub 2021 May 27.

Abstract

EGCG and quercetin are flavonoids which usually co-exist in edible plants and they exhibit anti-diabetes effects. This study aimed to explore the mechanisms by which quercetin and EGCG synergistically protected pancreatic β-cells from streptozotocin-induced apoptosis. EGCG, quercetin, and their combinations (both 15 μM) all reversed STZ-induced cells damage and enhanced glucose-stimulated insulin secretion, with the combination being more effective than a single compound. At the molecular level, the EGCG-quercetin combination upregulated BCL-2 expression and caused a greater reduction in miR-16-5p level than EGCG alone or quercetin alone. Overexpression of miR-16-5p could offset the down-regulated apoptotic genes caused by the synergistic action of the combination. These findings suggest that EGCG and quercetin exert synergistic anti-diabetes effect, possibly via decreasing the expression of miR-16-5p that targets directly BCL-2. This is the first report on a miRNA-based mechanism underlying the synergistic protective effect of EGCG and quercetin against pancreatic cell damage.

Keywords: BCL-2; EGCG; diabetes; miR-16-5p; quercetin; synergism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / metabolism
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Cell Line
  • Down-Regulation / drug effects
  • Drug Synergism
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / pathology
  • Mice
  • MicroRNAs / genetics*
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Quercetin / pharmacology*
  • Streptozocin / adverse effects
  • Up-Regulation / drug effects

Substances

  • Antioxidants
  • MicroRNAs
  • Mirn16 microRNA, mouse
  • Proto-Oncogene Proteins c-bcl-2
  • Bcl2 protein, mouse
  • Streptozocin
  • Catechin
  • Quercetin
  • epigallocatechin gallate