权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of a quick neutralization therapy for the diseases caused by bacterial toxins

开发针对细菌毒素引起的疾病的快速中和疗法

基本信息

批准号：
15209016
负责人：
NODA Masatoshi
金额：
$ 29.7万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

项目摘要

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 … More 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

本研究通过化学合成方法鉴定并验证了对霍乱弧菌的霍乱毒素（CT）、肠出血性大肠杆菌的Vero毒素（VT）和肉毒梭菌的肉毒毒素（BT）等毒力因子具有抑制作用的活性成分。汉方制剂Dio-kanzo-to抑制CT活性（即，ADP-核糖基化，中国仓鼠卵巢细胞伸长）;在Daio-kanzo-to中，Dio（黄芪）负责该效应。在从迪奥提取物中纯化的几种成分中，大黄没食子酰单宁（RG-单宁），一种以聚没食子酸酯结构为特征的化合物，是最有效的。为了确定活性成分，合成了类似于RG-单宁的没食子酸酯类似物。这些没食子酸酯化合物抑制所有CT活性，包括ADP-核糖基化、中国仓鼠卵巢细胞的伸长，重要的是，回肠袢中的液体积聚。苹果多酚对CT也有类似的抑制作用 ...更多信息从啤酒花苞叶中提取的多酚类物质（HBT）在体内外均能抑制VT活性，且呈浓度依赖性。几种未经纯化的植物多酚在动物实验中对BT有抑制作用。幽门螺杆菌（H.pylori）的溶血性细胞毒素（VacA）是H.pylori的重要毒力因子之一，与H. pylori引起的胃炎和溃疡有关。我们在这里报告，几种天然存在的多酚抑制VacA活性在体外和体内。其中啤酒花苞叶单宁（HBT）的抑制活性最强。HBT以浓度依赖性方式抑制VacA与其受体RPTPa和RPTPb的结合、其摄取以及易感细胞中的空泡化。此外，口服给予VacA与HBT的小鼠，减少VacA诱导的胃损伤在48小时。HBT与VacA直接相互作用形成复合物。总之，这些观察结果表明，HBT可以抑制幽门螺杆菌VacA引起的炎症和溃疡的发展，这表明HBT可以用作预防VacA引起的胃溃疡和炎症的新型药剂。几个自然的-天然多酚类物质，包括水果多酚，可能是有效的口服补液治疗和中和治疗这些细菌引起的疾病，毒素较少