I am curious what people know about quercetin and its effect on SIRT1. I have read numerous places that the metabolites of quercetin actually inhibit SIRT1 activity, while quercetin itself is an activator. I found this article that I posted below, but I cannot access the full article. Has anyone read it and what can you conclude from it? Basically, I am wondering if the quercetin has a greater activating effect than the metabolites have an inactivating effect. Any information on quercetin and it's role with resveratrol would be appreciated. Thanks!
SIRT1 stimulation by polyphenols is affected by their stability and metabolism.
Vincent C J de Boer, Marcus C de Goffau, Ilja C W Arts, Peter C H Hollman, Jaap Keijer
Silent information regulator two ortholog 1 (SIRT1) is the human ortholog of the yeast sir2 protein; one of the most important regulators of lifespan extension by caloric restriction in several organisms. Dietary polyphenols, abundant in vegetables, fruits, cereals, wine and tea, were reported to stimulate the deacetylase activity of recombinant SIRT1 protein and could therefore be potential regulators of aging associated processes. However, inconsistent data between effects of polyphenols on the recombinant SIRT1 and on in vivo SIRT1, led us to investigate the influence of (1) stability of polyphenols under experimental conditions and (2) metabolism of polyphenols in human HT29 cells, on stimulation of SIRT1. With an improved SIRT1 deacetylation assay we found three new polyphenolic stimulators. Epigallocatechin galate (EGCg, 1.76-fold), epicatechin galate (ECg, 1.85-fold) and myricetin (3.19-fold) stimulated SIRT1 under stabilizing conditions, whereas without stabilization, these polyphenols strongly inhibited SIRT1, probably due to H(2)O(2) formation. Using metabolically active HT29 cells we were able to show that quercetin (a stimulator of recombinant SIRT1) could not stimulate intracellular SIRT1. The major quercetin metabolite in humans, quercetin 3-O-glucuronide, slightly inhibited the recombinant SIRT1 activity which explains the lack of stimulatory action of quercetin in HT29 cells. This study shows that the stimulation of SIRT1 is strongly affected by polyphenol stability and metabolism, therefore extrapolation of in vitro SIRT1 stimulation results to physiological effects should be done with caution.