Biology Reference
In-Depth Information
the other hand, promoting apoptosis of
tumour-derived cell lines (Yamamoto
et al.
,
2003).
Investigating
in vivo
antioxidant prop-
erties of natural polyphenols has become a
complex challenge for many researchers.
The sound case reported by Lotito and Frei
(2004) is emblematic. They reported that,
after whole-apple consumption, serum anti-
oxidant capacity was significantly increased.
They demonstrate, however, that such ele-
vation was actually associated with
increased serum levels of uric acid.
Moreover, this uric acid derives from the
metabolic processing of the fructose con-
tained in apples. In addition, recent find-
ings published in
Hypertension
(Webb
et al.
,
2008) suggest that anti-hypertensive, vaso-
protective and anti-platelet effects of many
fruits could be associated with their nitrate
concentration. In fact, in healthy volunteers,
oral intake of beet juice (500 ml) produced a
significant lowering of blood pressure,
which in all cases was coincident with a
plasmatic peak of nitrate. Also, a positive
effect of the intake of beet juice on endothe-
lial function was observed. Webb and co-
workers (2008) proposed that entero-salival
reconversion (promoted by anaerobic bacte-
ria located in the tongue surface) of nitrate-
to-nitrite helps to further the production of
nitric oxide (NO) in the acidic gastric envi-
ronment. At the portal level, nitric oxide
can be re-oxidized into nitrite and finally
converted to NO, particularly in sites where
vessel stenosis exists. An increase in the
levels of NO could render additional benefit
in cases where gastric mucosa is injured by
long-term treatment with non-steroidal anti-
inflammatory drugs (NSAID) or infected
with highly virulent strains of
Helicobacter
pylori.
Moreover, it has been observed that
in the stomach certain polyphenols promote
a rapid NO non-enzymatic formation caus-
ing relaxing effects on the vascular smooth
muscle (Rocha
et al.
, 2009). An elevation in
NO derived from nitrite previously gener-
ated by the tongue bacteria (Peri
et al.
, 2005)
has been reported for apples (apple pulp is
rich in chlorogenic acid). Hence, growing
evidence confirms that some of the biologi-
cal activities of polyphenols do not require
high plasmatic concentrations. These data
suggest to us that the first (even the most
relevant) site of action for these molecules
is the gastrointestinal tract (see above).
2.3 Is the Intestinal Tract the First
Target for Polyphenolic Antioxidants?
It is well known that antioxidant activity
seems to be associated with specific vegetal
species used for medical or food purposes.
Moreover, such properties are limited to a
few families of secondary metabolites. For
example, anthocyanidins are common to
many berries, whereas glucosinolates are
exclusive to cruciferous plants (broccoli).
Among these substances, polyphenols are
the most consumed. As said above, the data
relating to the absorption, metabolism and
excretion of polyphenols are poor and very
contradictory so many researchers doubt
their systemic antioxidant effects after oral
intake. So, it has been suggested that the
first and maybe the most relevant site of
antioxidant action of dietary polyphenols is
the gastrointestinal tract (reviewed by
Clifford, 2004). Several studies have dem-
onstrated that only certain polyphenols
could be intestinally absorbed. Also, it
should be considered that only a part of the
bioavailable polyphenols circulate in its
free forms reaching 5-10% of the initial
ingested portion. Hence, polyphenols
circulate as conjugated forms such as glu-
curonides, sulfates and methyl derivates.
Nevertheless, the concentration of these
conjugated forms still is extremely low.
It is therefore very difficult to carry out
real pharmacokinetic studies because nor-
mally urine or serum samples must be pre-
treated with a-glucosidase and/or sulfatase
in order to release the aglicones. Such pseu-
dopharmacokinetic studies had led to the
conclusion that polyphenol serum concen-
trations are low, very variable and with
transient maxima (T
max
= 1-2.5 h). Overall,
it is unlikely that conjugate forms exceed
concentrations of about 10 mM or 1 mM in
the case of aglicone forms. Because it is
clear that much of the polyphenols are not
Search WWH ::
Custom Search