Myricetin Protects Against Cytokine-Induced Cell Death in RIN-m5f β Cells

Cytokine-induced cell death is recognized as a major cause of progressive beta-cell loss. Tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), and interferon gamma (IFN-gamma) in combination trigger a series of events that lead to beta-cell death. In the past few decades, the use of myricetin as an anti-inflammatory and cytoprotective agent has gained much attention. The present study focused on the protective roles of myricetin against cytokine-induced cell death in insulin-secreting RIN-m5f beta cells. The results showed that myricetin (especially at concentrations of 10 mu M and 20 mu M) increased cell viability and decreased cell apoptosis induced by the cytokine mixture of TNF-alpha (10 ng/mL), IL-1 beta (5 ng/mL), and IFN-gamma (1000 IU/mL) for 3 days. Moreover, the cytokines increased the total and p65 subunit levels of nuclear factor kappa B, decreased inhibitor kappa B alpha levels, stimulated the accumulation of nitric oxide, increased cytochrome c release from mitochondria, and induced reactive oxygen species generation; myricetin (especially at the concentration of 20 mu M) abolished all of these parameters. These results suggest that myricetin might have therapeutic value for preventing beta-cell death.