Biology Reference
In-Depth Information
VacA toxin represents a potential mecha-
nism of neutralization for the different viru-
lence factors of this bacterium. These
compounds were effective in blocking the
binding of VacA to its receptors RPTPa and
RPTPb, inhibiting the non-specific binding
of VacA to cell membranes, decreasing the
cell vacuolation in vitro and significantly
diminishing VacA-induced gastritis in mice.
Likewise, it was demonstrated that the
administration of red wine extract and/or
green tea promoted a clear gastroprotective
effect in mice infected with H. pylori or
treated with purified VacA. These data sug-
gest that VacA would be a potential molecu-
lar target for certain wine and green tea
polyphenols (Ruggiero et al ., 2007).
Interestingly, it was found that quince pulp
extracts compared with apple pulp extracts
have a higher antiulcerogenic effect on etha-
nol and HCl-induced gastric injury (Hamauzu
et al ., 2006). The authors suggest that the
difference in the effectiveness of such anti-
ulcerogenic extracts lie in the significantly
higher concentration of procyanidins, with
a high degree of polymerization present in
quince pulp ( DPm = 29) versus apple pulp
( DPm = 3). Unlike apple pulp, however,
peel is particularly rich in procyanidins
with high mean degree of polymerization
( DPm = 15-190) (Shibusawa et al ., 2001).
Saito et al. (1998) previously reported
that seed extracts of Vitis vinifera and its
procyanidins (with a high molecular weight)
have an anti-ulcerogenic effect; the authors
postulated that part of this effect is due to
the strong binding of these compounds to
proteins present in the gastric mucosa,
allowing the formation of a protective local
barrier with potential antioxidant and
anti-inflammatory activities. Indeed, it was
recently established that polyphenol-
enriched extracts of apple pomace promote
antioxidant and cytoprotective effects in
primary cultures of gastric mucosal cells
(MKN-28) subjected to a xanthine-xanthine
oxidase system as a superoxide radical gen-
erator (Graziani et al ., 2005). The protective
effect of these extracts has been observed in
in vitro (Caco-2, AGS cells) and in vivo mod-
els of injury induced by co-administration
of indomethacin (Graziani et al ., 2005;
Carrasco-Pozo et al ., 2010, 2011a,b).
Interestingly, oxidative damage and gastric
mucosal lesions induced by indomethacin
are exacerbated by infection with H. pylori
(Arend et al ., 2005). In another study, it was
established that apple peel extract inhib-
ited, in vitro and in vivo , the activation of
the transcription factor AP-1 and neoplastic
transformation (Ding et al ., 2000). The acti-
vation of the AP-1 complex is one of the key
events in tumour promotion mediated by
the cytotoxin CagA of H. pylori . It has been
suggested that apple polyphenols could
inhibit the activation of the AP-1 signalling
pathway by interfering with the MAP
kinases ERK and JNK. In electron spin reso-
nance (ESR) experiments, Ding and col-
leagues (2000) confirmed the stabilizing
effect of apple peel extract on OH and O 2 •−
radicals. The latter would be particularly
relevant given that ERKs, JNKs and p38 are
molecules activated in response to oxidative
stimuli. Finally, the same authors showed
these extracts also inhibit tumour induction
in mice treated with 12-O-tetradecanoyl-
phorbol-13-acetate (TPA). The diverse
molecular targets for polyphenols during
the H. pylori infection process are summa-
rized in Fig. 2.3. Hence, polyphenols could
display their effects against H. pylori not
only affecting its viability but also its adher-
ence to gastric mucosa (1). Certain polyphe-
nols may have a mucosa cytoprotective
effect (2). The effect of polyphenols against
some virulence factors like VacA (3) or ure-
ase (4) could be explained by the formation
of inactive complexes. Finally, antioxidant
and anti-inflammatory effects associated
with polyphenol intake could be explained
by a inhibition of ROS and interleukin (IL-8)
production in those neutrophils activated
by H. pylori (5).
2.4 Polyphenols: What we Learn
Measuring the Antioxidant Capacity
The view on the importance of polyphenols
in human health has been extensively
revised (Kris-Etherton et al ., 2004; Manach
et al ., 2005; Williamson and Manach, 2005;
 
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