Extracts of Glycyrrhiza uralensis and Isoliquiritigenin Counteract Amyloid-β Toxicity in Caenorhabditis elegans
Extracts of Glycyrrhiza uralensis and Isoliquiritigenin Counteract Amyloid-β Toxicity in Caenorhabditis elegans
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DOI：
10.1055/s-0035-1545724
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发表时间：
2015-04-01
期刊：
影响因子：
2.7
通讯作者：
Wink, Michael
中科院分区：
文献类型：
--
作者：
Link, Pille;Wetterauer, Bernhard;Wink, Michael
随着越来越多的人步入老年，阿尔茨海默病对现代社会构成了日益严重的威胁。迄今为止，这种情况还没有有效的治疗方法。在这项研究中，我们研究了乌拉尔甘草对抗淀粉样蛋白毒性（阿尔茨海默病的关键特征之一）的潜力。 LC-MS/MS 分析表明，甘草酸和糖基化形式的异甘草素和甘草素是乌拉尔甘草水和甲醇提取物的主要成分。这些提取物和纯化合物分别在两种β-淀粉样蛋白聚集和β-淀粉样蛋白毒性的秀丽隐杆线虫模型中测试其活性。异甘草素处理后β-淀粉样蛋白聚集体数量减少30%，甲醇提取物可减少14%，甘草素和甘草酸可减少15%，甘草酸苷元甘草次酸可减少20%。提取物和异甘草素还对表达人类淀粉样β肽的转基因线虫中的急性淀粉样β毒性表现出显着的活性，分别延迟该模型中的麻痹1.8小时和1.1小时。我们的结论是，G. uralensis 的次级化合物可能成为治疗阿尔茨海默病的有趣候选药物，然而，需要在其他模型系统中进行进一步分析。
Alzheimer's disease is a rising threat for modern societies as more and more people reach old age. To date, there is no effective treatment for this condition. In this study, we investigated the potential of Glycyrrhiza uralensis to counteract amyloid-beta toxicity, one of the key features of Alzheimer's disease. An LC-MS/MS analysis revealed glycyrrhizic acid and glycosylated forms of isoliquiritigenin and liquiritigenin as major constituents of water and methanol extracts of G. uralensis. These extracts and the pure compounds were tested for their activity in two Caenorhabditis elegans models of amyloid-beta aggregation and amyloid-beta toxicity, respectively. The number of amyloid-beta aggregates decreased by 30% after treatment with isoliquiritigenin, the methanol extract could reduce the number by 14%, liquiritigenin and glycyrrhizic acid by 15%, and the aglycon of glycyrrhizic acid, glycyrrhetinic acid, by 20%. Both extracts and isoliquiritigenin also showed significant activity against acute amyloid-beta toxicity in transgenic C. elegans that express human amyloid-beta peptides, delaying the paralysis in this model by 1.8 h and 1.1 h, respectively. We conclude that secondary compounds of G. uralensis may become interesting drug candidates for the treatment of Alzheimer's disease, which, however, need further analysis in other model systems.