MORINAGA Naoko Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (20092108)
KUWABARA Satoshi Chiba University, Graduate School of Medicine, Associate Professor, 大学院・医学研究院, 助教授 (70282481)
MORI Masahiro Chiba University, Graduate School of Medicine, Assistant professor, 大学院・医学研究院, 助手 (70345023)
YAHIRO Kinnosuke Chiba University, Graduate School of Medicine, Assistant professor, 大学院・医学研究院, 助手 (80345024)
|Budget Amount *help
¥46,410,000 (Direct Cost: ¥35,700,000、Indirect Cost: ¥10,710,000)
Fiscal Year 2004: ¥20,150,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥4,650,000)
Fiscal Year 2003: ¥26,260,000 (Direct Cost: ¥20,200,000、Indirect Cost: ¥6,060,000)
Our studies were undertaken to identify and verify by chemical synthesis the active components that inhibited cholera toxin(CT) of Vibrio cholerae, vero toxin(VT) of enterohaemorragic Escherichia coli and botulinum toxin(BT) of Clostridium botulinum, the virulence factors secreted by these bacteria. The Kampo formulation, Dio-kanzo-to, inhibited CT activities (i.e., ADP-ribosylation, Chinese hamster ovary cell elongation) ; in Daio-kanzo-to, Dio(Rhei rhizoma) was responsible for this effect. Among several components purified from Dio extract, rhubarb galloyl-tannin(RG-tannin), a compound characterized by a polygallate structure, was the most effective. To define the active component, gallate analogues similar to RG-tannin were synthesized. These gallate compounds inhibited all CT activities including ADP-ribosylation, elongation of Chinese hamster ovary cells, and importantly, fluid accumulation in ileal loops. The similar inhibitory effect on CT was also found in apple polyphenols pur
ified from immature apples.
The polyphenols (HBT) purified from hop bract containing high molecular weight of polymerized catechin, inhibited VT activities in a concentration-dependent manner in vitro and in vivo. And several plant polyphenols which were not be purified yet inhibited BT in animal studies. Vacuolating cytotoxin, (VacA) of H.pylori is one of the important virulence factors and is responsible for H.pylori-induced gastritis and ulcer. We report here that several natural-occurring polyphenols inhibited VacA activity in vitro and in vivo. Especially, hop bract tannin(HBT) had the strongest inhibitory activity among the other polyphenols investigated. In a concentration-dependent manner HBT inhibited VacA binding to its receptors, RPTPa and RPTPb, its uptake, and vacuolation in susceptible cells. In addition, oral administration of VacA with HBT to mice, reduced VacA-induced gastric damage at 48 h. HBT and VacA interacted directly and formed a complex. Taken together, these observations indicate that HBT may suppress the development of inflammation and ulceration by H.pylori VacA, suggesting that HBT may be useful as a new type of agent for the prevention of gastric ulcer and inflammation caused by VacA.
Thus, several natural-occurring polyphenols including fruit polyphenols might be effective adjunctive therapy with oral rehydration solution and neutralization therapy forthe diseases caused by these bacterial toxins Less