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

Quercetin, existing mostly in its glycoside form quercitrin, is the mostwidely distributed flavonoid in nature. It possesses various potential effectsas an antioxidant, anti-inflammatory for cell damage of β-cells, however, studieson this topic are limited and controversial. In order to examine the effects ofquercetin on type I diabetes mellitus, we investigated the role of quercetin/quercitrinin 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 expressionwere measured with or without quercetin/quercitrin treatment. We also comparedthe differences between the aglycone and the glycoside forms of quercetin, withthe aim to shed some light on their structures and transportation into cells.The results showed that quercetin/quercitrin protected against cytokine-inducedcell death, improved GSIS, and inhibited ROS as well as NO accumulation. Theseeffects were associated with reduced expression of inducible nitric oxide synthases(iNOS) and inhibited translocation of nuclear factor-κB (NF-κB). Also, quercetin/quercitrinsuppressed cytochrome c release from mitochondria and the following alterationof downstream proteins, suggesting that mitochondrial apoptosis was attenuatedby quercetin treatment. In summary, quercetin and quercitrin are potential candidatesto prevent β-cell death via the mitochondrial pathway and NF-κB signaling, andquercetin may be more efficacious than quercitrin as an anti-diabetic agent.