Who cares about bioavailability when greater than 75% is absorbed and converted to sulfates that get into cells better than RESV itself?
What is the evidence that the sulfate conjugates get into cells better than rsv itself? I haven't run across it in the literature. Generally speaking, decreasing the hydrophobicity of a molecule, such as via conjugation, makes it less likely to traverse the cell membrane. There may be active transport in some cases (glyco-conjugates?). Further, for resveratrol metabolites to be active, you have to either postulate that the conjugates bind and elicit the same response as resveratrol in a site that does not seem to be very accommodating from the structure activity relationships that I'm aware of, or else there need to be intracellular sulfatases in the tissues where you expect it to have an effect. I would love to learn that resveratrol metabolites were active, but what's the evidence?
ACT: Resveratrol is a natural product with diverse biological activities. We have
previously reported that resveratrol possesses potent synergistic inhibitory activity
against human immunodeficiency virus (HIV)-1 infection in combination with nucleoside
analogs (Heredia et al. 2000. J Acquir Immune Defic Syndr 25:246–255). As a part of
our program in developing resveratrol as a component for anti-HIV chemotherapy,
we describe in this article the characterization, chemical synthesis, and biological effects
of the human metabolites of resveratrol. We found that resveratrol was metabolized in
humans into two metabolites, which were characterized as resveratrol-3-O- and 40-Oglucuronides.
For further biological studies, we reported two simple, alternative methods
for the synthesis of the metabolites. The cytotoxic and antiviral activities of resveratrol
and its metabolites were compared in cell culture experiments using human peripheral
blood mononuclear cells. Whereas resveratrol was cytotoxic at 30 mM, no cytotoxicity
was observed for the metabolites at concentrations as high as 300 mM. However,
resveratrol showed strong synergistic anti-HIV activity with didanosine at 10 mM, but
no synergistic effects were observed for either of the metabolites at up to 300 mM.
Nevertheless, the in vitro activity of the metabolites (resveratrol glucuronides) may not
necessarily reflect their in vivo function, given the fact that the ubiquitously existing
human b-glucuronidase could convert the metabolites back to resveratrol locally or
systematically in vivo. The present studies have implications for future development of
resveratrol and/or its derivatives as a chemotherapeutic agent. 2004
We further demonstrated that, in contrast to resveratrol, the
metabolites are neither active against HIV-1
infection nor cytotoxic at up to 300 mM in cell
culture experiments, but the in vitro behavior of
the metabolites may not necessarily reflect their
in vivo function, given the fact that the ubiquitously
existing human b-glucuronidase could convert
the metabolites back to resveratrol either
locally or systematically in vivo.