Extracts of Glycyrrhiza uralensis and Isoliquiritigenin Counteract Amyloid-β Toxicity in Caenorhabditis elegans

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.