Maybe maxwatt can answer some of my questions, i'm sure you're out here
I need your expertise on the resveratrol issue.
Can you explain to me why the action of resveratrol can be significant or at least exist if the substance is only in the plasma for a short period of time.
Is this short period long enough for activating or producing effects that are benfical for health ?
btw i found this study which is suggesting that resveratrol alters the downstream pathway of sirtuin instead of activating it.Isn't constant altering of a pathway needed for creating an effect ?
Stefani M, Markus MA, Lin RC, Pinese M, Dawes IW, Morris BJ.
D.Sc., Basic & Clinical Genomics Laboratory, School of Medical Sciences and Bosch Institute, Bldg. F13, The University of Sydney, Sydney, New South Wales 2006, Australia. brianm@medsci.usyd.edu.au.
The natural polyphenol resveratrol stimulates sirtuins and extends lifespan. Here resveratrol inhibited expression of replicative senescence marker INK4a in human dermal fibroblasts, and 47 of 19,000 genes from microarray experiments were differentially expressed. These included genes for growth, cell division, cell signaling, apoptosis, and transcription. Genes involved in Ras and ubiquitin pathways, Ras-GRF1, RAC3, and UBE2D3, were downregulated. The changes suggest resveratrol might alter sirtuin-regulated downstream pathways, rather than sirtuin activity. Serum deprivation and high confluency caused nuclear translocation of the SIRT1-regulated transcription factor FOXO3a. Our data indicate resveratrol's actions might cause FOXO recruitment to the nucleus.
Sinclair and Westphal have stated they mapped the Sirt1 gene, and know how resveratrol docks to it, and that they have used this knowledge to design their more effective NCE's for activation of sirtuins 1000 times more effectively than resveratrol.
In short, I think the study you cited implied the wrong conclussion; they did say
"might alter" not
"does alter".
If resveratrol activates a gene, the gene would, I think, stay activated for a period even when resveratrol has cleared the blood, or perhaps only a very tiny amount of resveratrol need stay linked to the genes? There may also be an active transport mechanism, whereby resveratrol is bound by lipoproteins in the blood, which may affect measured blood levels:
This was discussed here:
See this post Post 992
The study:
Biochem Pharmacol. 2004 Sep 15;68(6):1113-8.
Transport of resveratrol, a cancer chemopreventive agent, to cellular targets: plasmatic protein binding and cell uptake.Jannin B, Menzel M, Berlot JP, Delmas D, Lançon A, Latruffe N.
Laboratoire de Biologie Moléculaire et Cellulaire, Université de Bourgogne, 6 boulevard Gabriel, 21000 Dijon, France.
Resveratrol produced by several plants, berries and fruits, including grapes, is one of the best known natural food microcomponents with potent chemopreventive properties towards the most severe contemporary human diseases: cardiovascular sickness, cancer and neurodegenerative pathologies. Demonstration of its mechanism of action also implies the elucidation of the steps of bioavailability and bioabsorption in cells and tissues. In order to estimate the relationships between the amounts of resveratrol taken up by food or drink intake, and the several possible benefits illustrated from in vitro/in vivo experiments and from epidemiological studies, it is essential to demonstrate step by step the route of resveratrol from plasma to the cell active site. In plasma, resveratrol was shown to interact with lipoproteins. This commentary also contains previously unpublished results about interactions between resveratrol and albumin and the enhancement of this binding in presence of fatty acids. We have previously described that resveratrol uptake by hepatic cells involves two processes--a passive one and a carrier-mediated one. Thanks to this last process, resveratrol, while tightly bound to blood proteins, could be largely delivered to body tissues. The intracellular proteic targets of resveratrol remain to be identified.
PMID: 15313407
Edited by maxwatt, 28 November 2007 - 12:37 PM.
