Studies on Natural Anti-ulcer Agents based on Eradication of Helicobacter pylori

基于绿茶儿茶素和可可中的多酚类物质具有抗幽门螺杆菌(Hp)的活性这一事实，对豆科、香叶科、大戟科、桦树科和蝴蝶科植物中的多酚成分进行了研究，以寻找有效的抗幽门螺杆菌活性物质。本研究共分离出27个新的抗氧化多酚类化合物，包括黄酮类、单宁水解性单体和低聚物，以及7个新的具有杀鱼活性的虹膜类三萜类化合物。根据波谱和化学证据对它们的结构进行了鉴定。其中，水解性单宁具有较强的抗幽门螺杆菌活性，其MIC值为3.13~12.5μg/ml，原花青素和EGCG的MIC值为12.5~100μg/ml，其中最强的抗幽门螺杆菌活性为灯盏花素I、柯里拉京和顺丁宁。这种活动是杀菌的，但不是统计学上的。这些活性多酚对常见致病菌如大肠埃希菌、金黄色葡萄球菌、枯草杆菌和铜绿假单胞菌均不敏感，表明它们对Hp具有特异性作用，并与β-内酰胺类药物对耐甲氧西林金黄色葡萄球菌有协同作用。加入这些单宁(50μg/ml)后，苯唑西林对MRSA的最低抑菌浓度降至1/100~1/500，是一种有希望克服MRSA的策略。此外，可水解单宁对超氧阴离子和/或化合物48/80诱导的大鼠肥大细胞的组胺释放有抑制作用。

Based on the fact that polyphenolics such as green tea catechins and polyphenols in cocoa are known to show anti-Helicobacter pylori (HP) activity, polyphenolic components of various species of Leguminosae, Geraniaceae, Euphorbiaceae, Betulaceae and Iridaceae were examined in order to discover effective anti-HP agents. This study led to the isolation of 27 new antioxidative polyphenolics, which include flavonoids, hydrolysable tannin monomers and oligomers, and 7 new iridal-type triterpenoids with piscicidal activity. Their structures were elucidated on the basis of spectral and chemical evidence. Among these compounds, hydrolysable tannins exhibited potent anti-HP activity with MIC 3.13〜12.5μg/ml, whereas procyanidins and EGCG had MIC 12.5〜100μg/ml. The most potent anti-HP activity was exhibited by tellimagrandin I, corilagin and strictinin. This activity was bactericidal, but not statistical. These active polyphenols were not sensitive to ordinary pathogenic bacteria such as Escherichia coli, Staphylococcus aureus, Batilus subtilis and Pseudomonus aeruginosa, indicating their specific action to HP.Tellimagrandin I and corilagin were also found to have synergestic action with β-lactam on methicillin-resistant Staphylococcus aureus (MRSA). The MIC of oxacillin against MRSA was reduced to 1/100〜1/500 upon addition of these tannins (50μg/ml), suggesting a promising strategy to overcome the MRSA.In addition, the hydrolyzable tannins showed inhibitory effects on histamine-release from rat mast cells, which was induced by superoxide anion and/or compound 48/80.