title: Extracts of Glycyrrhiza uralensis and isoliquiritigenin counteract amyloid-β toxicity in Caenorhabditis elegans.
abstract: 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-β 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-β aggregation and amyloid-β toxicity, respectively. The number of amyloid-β 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-β toxicity in transgenic C. elegans that express human amyloid-β 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.
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
authors.forename: Pille
authors.initials: P
authors.lastname: Link
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wetterauer
authors.affiliation: Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Wink
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D047188:Chalcones / Q000494:pharmacology* / Q000627:therapeutic use; D044950:Flavanones / Q000494:pharmacology* / Q000627:therapeutic use; D006034:Glycyrrhetinic Acid / Q000494:pharmacology / Q000627:therapeutic use; D029882:Glycyrrhiza uralensis / Q000737:chemistry*; D019695:Glycyrrhizic Acid / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D047188:Chalcones; D044950:Flavanones; D010936:Plant Extracts; D019695:Glycyrrhizic Acid; C040920:isoliquiritigenin; D006034:Glycyrrhetinic Acid; C083152:liquiritigenin