Abstract
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. 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. 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. 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.
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