Resveratrol up-regulates SIRT1 and inhibits cellular oxidative stress in the diabetic milieu: mechanistic insights

Abstract

Several lines of evidence support a role for oxidative stress in diabetic complications Diabetic patients have increased O2− production in monocytes. Loss of SIRT1 activity may be associated with metabolic diseases such as diabetes. Several studies have shown that SIRT1 can regulate mammalian FOXO transcription factors through direct binding and/or deacetylation. However, interactions between SIRT1 and FOXO under diabetic conditions are unclear. The phytochemical resveratrol, has recently gained attention for its protection against metabolic disease. Resveratrol has been shown to increase mitochondrial function by activating SIRT1. In this study, we tested the protective effect of resveratrol on cellular oxidative stress through the SIRT1-FOXO pathway under high-glucose conditions. Human monocytic (THP-1) cells were cultured in presence of mannitol (osmolar control) or normoglycemic (NG, 5.5 mmol/L glucose) or hyperglycemic (HG, 25 mmol/L glucose) conditions in absence or presence of resveratrol (3 and 6 µmol/L) for 48 h. We first examined SIRT1 activity and oxidative stress in monocytes of T1DM patients compared to healthy controls. In T1DM patients, monocytic SIRT1 expression was significantly decreased and p47phox expression was increased compared to controls. Under HG in vitro, SIRT1 and FOXO3a were significantly decreased compared to NG, this was reversed by resveratrol treatment, concomitant with reduction in HG-induced superoxide production and p47phox. Under HG, SIRT1 small interfering RNA (siRNA), inhibited FOXO3a and there was no beneficial effect of resveratrol in siRNA treated HG-induced cells. Thus, resveratrol decreases HG-induced superoxide production via upregulation of SIRT1, induction of FOXO3a and inhibition of p47phox in monocytes.

Enzymatic Biosynthesis of Novel Resveratrol Glucoside and Glycoside Derivatives

“…Upregulation of SIRT1 has also been shown to reduce cellular oxidative stress in the diabetic milieu (68). In this study, we attempted to expand the number of resveratrol derivatives by means of an enzymatic glycosylation approach that could help to generate novel therapeutics.…”

Resveratrol alleviates endotoxemia-associated adrenal insufficiency by suppressing oxidative/nitrative stress

“…Previous study has demonstrated that resveratrol exerts antioxidant effects via upregulation of SIRT1 expression [19]. Therefore, we examined whether resveratrol affected SIRT1 expression in adrenal glands during endotoxemia.…”

Post-translational modifications of FOXO family proteins

“…Resveratrol can increase the SIRT1 deacetylation activity, which reduces FOXO1 and FOXO3a acetylation and increases the nucleus localization, resulting stronger transcriptional activity. Resveratrol activates AMPK, which increases the deacetylase activity of SIRT1, and further increases the FOXO1 transcription activity (92,93). Studies have demonstrated that certain proteins form complexes with FOXO-SIRT1.…”