RT Journal Article
SR Electronic
T1 Differential Cell-Protective Function of Two Resveratrol (<em>Trans</em>-3,5,4′-trihydroxystilbene) Glucosides against Oxidative Stress
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 124
OP 132
DO 10.1124/jpet.112.198937
VO 344
IS 1
A1 Ryusuke Hosoda
A1 Atsushi Kuno
A1 Yusuke S. Hori
A1 Katsuki Ohtani
A1 Nobutaka Wakamiya
A1 Azusa Oohiro
A1 Hiroki Hamada
A1 Yoshiyuki Horio
YR 2013
UL http://jpet.aspetjournals.org/content/344/1/124.abstract
AB Resveratrol (trans-3,5,4′-trihydroxystilbene; RSV), a natural polyphenol, exerts a beneficial effect on health and diseases. RSV targets and activates the NAD+-dependent protein deacetylase SIRT1; in turn, SIRT1 induces an intracellular antioxidative mechanism by inducing mitochondrial superoxide dismutase (SOD2). Most RSV found in plants is glycosylated, and the effect of these glycosylated forms on SIRT1 has not been studied. In this study, we compared the effects of RSV and two glycosyl RSVs, resveratrol-3-O-β-d-glucoside (3G-RSV; polydatin/piceid) and resveratrol-4′-O-β-d-glucoside (4′G-RSV), at the cellular level. In oxygen radical absorbance capacity and 2,2-diphenyl-1-picrylhydrazyl radical scavenging assays, the antioxidant activity of 3G-RSV was comparable to that of RSV, whereas the radical-scavenging efficiency of 4′G-RSV was less than 50% of that of RSV. However, 4′G-RSV, but not 3G-RSV, induced SIRT1-dependent histone H3 deacetylation and SOD2 expression in mouse C2C12 skeletal myoblasts; as with RSV, SIRT1 knockdown blunted these effects. RSV and 4′G-RSV, but not 3G-RSV, mitigated oxidative stress–induced cell death in C2C12 cells and primary neonatal rat cardiomyocytes. RSV and 4′G-RSV inhibited C2C12 cell proliferation, but 3G-RSV did not. RSV was found in both the intracellular and extracellular fractions of C2C12 cells that had been incubated with 4′G-RSV, indicating that 4′G-RSV was extracellularly deglycosylated to RSV, which was then taken up by the cells. C2C12 cells did not deglycosylate 3G-RSV. Our results point to 4′G-RSV as a useful RSV prodrug with high water solubility. These data also show that the in vitro antioxidative activity of these molecules did not correlate with their ability to protect cells from oxidative stress–induced apoptosis.