Inhibitory effects of polyphenols on gastric injury by Helicobacter pylori VacA toxin.
BACKGROUND
Helicobacter pylori induces gastric damage and may be involved in the pathogenesis of gastric cancer. H. pylori-vacuolating cytotoxin, VacA, is one of the important virulence factors, and is responsible for H. pylori-induced gastritis and ulceration. The aim of this study is to assess whether several naturally occurring polyphenols inhibit VacA activities in vitro and in vivo.


METHODS
Effects of polyphenols on VacA were quantified by the inhibition of: 1, vacuolation; 2, VacA binding to AZ-521 or G401 cells or its receptors; 3, VacA internalization. Effects of hop bract extract (HBT) containing high molecular weight polymerized catechin on VacA in vivo were investigated by quantifying gastric damage after oral administration of toxins to mice.


RESULTS
HBT had the strongest inhibitory activity among the polyphenols investigated. HBT inhibited, in a concentration-dependent manner: 1, VacA binding to its receptors, RPTP(alpha) and RPTP(beta); 2, VacA uptake; 3, VacA-induced vacuolation in susceptible cells. In addition, oral administration of HBT with VacA to mice reduced VacA-induced gastric damage at 48 hours. In vitro, VacA formed a complex with HBT.


CONCLUSIONS
HBT may suppress the development of inflammation and ulceration caused by H. pylori VacA, suggesting that HBT may be useful as a new type of therapeutic agent for the prevention of gastric ulcer and inflammation caused by VacA.
Yahiro
Kinnosuke
K
Department of Molecular Infectiology, Graduate School of Medicine, Chiba University, Chiba, Japan.
Shirasaka
Daisuke
D
Tagashira
Motoyuki
M
Wada
Akihiro
A
Morinaga
Naoko
N
Kuroda
Fuminobu
F
Choi
Oksun
O
Inoue
Masahito
M
Aoyama
Nobuo
N
Ikeda
Mitsuo
M
Hirayama
Toshiya
T
Moss
Joel
J
Noda
Masatoshi
M
D000284:Administration, Oral; D000818:Animals; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002392:Catechin / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D005419:Flavonoids / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D005753:Gastric Mucosa / Q000187:drug effects* / Q000382:microbiology / Q000473:pathology*; D005756:Gastritis / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D016480:Helicobacter pylori / Q000472:pathogenicity*; D006801:Humans; D027582:Humulus / Q000737:chemistry; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D010636:Phenols / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D010936:Plant Extracts / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D059808:Polyphenols
D001426:Bacterial Proteins; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; C074689:VacA protein, Helicobacter pylori; D002392:Catechin