Quercetin and quercitrin protect against cytokine‑induced injuries in RINm5F β-cells via the mitochondrial pathway and NF-κB signaling

Int J Mol Med. 2013 Jan;31(1):265-71. doi: 10.3892/ijmm.2012.1177. Epub 2012 Nov 8.


Quercetin, existing mostly in its glycoside form quercitrin, is the most widely distributed flavonoid in nature. It possesses various potential effects as an antioxidant, anti-inflammatory for cell damage of β-cells, however, studies on this topic are limited and controversial. In order to examine the effects of quercetin on type I diabetes mellitus, we investigated the role of quercetin/quercitrin in cytokine-induced β-cell injuries in RINm5F rat insulinoma cells. Cell viability, glucose-stimulated insulin secretion (GSIS), intracellular reactive oxygen species (ROS), nitric oxide (NO) and inflammation or apoptosis-associated protein expression were measured with or without quercetin/quercitrin treatment. We also compared the differences between the aglycone and the glycoside forms of quercetin, with the aim to shed some light on their structures and transportation into cells. The results showed that quercetin/quercitrin protected against cytokine-induced cell death, improved GSIS, and inhibited ROS as well as NO accumulation. These effects were associated with reduced expression of inducible nitric oxide synthases (iNOS) and inhibited translocation of nuclear factor-κB (NF-κB). Also, quercetin/quercitrin suppressed cytochrome c release from mitochondria and the following alteration of downstream proteins, suggesting that mitochondrial apoptosis was attenuated by quercetin treatment. In summary, quercetin and quercitrin are potential candidates to prevent β-cell death via the mitochondrial pathway and NF-κB signaling, and quercetin may be more efficacious than quercitrin as an anti-diabetic agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytochromes c / metabolism
  • Cytokines / adverse effects*
  • Glucose / metabolism
  • Hypoglycemic Agents / pharmacology*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects*
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Insulinoma / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Quercetin / analogs & derivatives*
  • Quercetin / pharmacology
  • Rats
  • Reactive Oxygen Species
  • Signal Transduction


  • Cytokines
  • Hypoglycemic Agents
  • Insulin
  • NF-kappa B
  • Reactive Oxygen Species
  • quercitrin
  • Nitric Oxide
  • Cytochromes c
  • Quercetin
  • Nitric Oxide Synthase Type II
  • Nos2 protein, rat
  • Glucose