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May 27, 2013: by Bill Sardi
Well, that is oft repeated statement by mindless biologists who don’t really delve into this matter. Technically they are correct. Resveratrol is fully metabolized (taken out of action) after it has made a few passes through the liver (a process that can be delayed by taking quercetin with resveratrol). Liver metabolism involves coupling resveratrol with detoxification molecules (sulfate, glucuronate) produced in the liver. Resveratrol is then too large a molecule coupled to a carrier protein to pass through cells walls and influence genetic machinery inside cells. However, an enzyme (glucuronidase) that is abundant at sites of inflammation, infection and malignancy unlocks resveratrol at the right time and place, freeing it to switch genes and act as an important copper-binding antioxidant. The very fact resveratrol produces systemic-wide biological effects in compartmentalized organs such as the brain, heart, kidneys, suggests it is biologically active, even passing the blood-brain barrier.
Now researchers in China address bioavailability by showing resveratrol and resveratrol bound to glucuronate bind to albumin, deters oxidation (hardening) of cholesterol, inflammation and growth of tumor cells. In other words, its metabolite forms are com parable in biological action to resveratrol. Argument over: resveratrol exerts biological activity as a free unbound molecule and when bound to detoxification molecules. ©2013 Bill Sardi, Resveratrol News.com
Chembiochem 2013 May 23. doi: 10.1002/cbic.201300080. [Epub ahead of print]
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, 222 Tianshui Street S., Lanzhou 730000 (China).
Resveratrol (3,5,4′-trihydroxystilbene, RES), a star among dietary polyphenols, shows a wide range of biological activities, but it is rapidly and extensively metabolized into its glucuronide and sulfate conjugates as well as to the corresponding reduced products. This begs the question of whether the metabolites of RES contribute to its in vivo biological activity. To explore this possibility, we synthesized its glucuronidation (3-GR and 4′-GR) and reduction (DHR) metabolites, and evaluated the effect of these structure modifications on biological activities, including binding ability with human serum albumin (HSA), antioxidant activity in homogeneous solutions and heterogeneous media, anti-inflammatory activity, and cytotoxicity against various cancer cell lines. We found that 1) 4′-GR, DHR and RES show nearly equal binding to HSA, mainly through hydrogen bonding, whereas 3-GR adopts a quite different orientation mode upon binding, thereby resulting in reduced ability; 2) 3-GR shows comparable (even equal) ability to RES in FRAP- and AAPH-induced DNA strand breakage assays; DHR, 3-GR, and 4′-GR exhibit anti-hemolysis activity comparable to that of RES; additionally, 3-GR and DHR retain some degree activity of the parent molecule in DPPH. -scavenging and cupric ion-initiated oxidation of LDL assays, respectively; 3) compared to RES, 4′-GR displays equipotent ability in the inhibition of COX-2, and DHR presents comparable activity in inhibiting NO production and growth of SMMC-7721 cells. Relative to RES, its glucuronidation and reduction metabolites showed equal, comparable, or some degree of activity in the above assays, depending on the specific compound and test model, which probably supports their roles in contributing to the in vivo biological activities of the parent molecule.
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