Liquiritigenin inhibits Aβ25-35-induced neurotoxicity and secretion of Aβ1-40 in rat hippocampal neurons

Aim： To examine whether liquiritigenin, a newly found agonist of selective estrogen receptor-β, has neuroprotective activity against β-amyloid peptide （Aβ） in rat hippocampal neurons.
Methods： Primary cultures of rat hippocampal neurons were pretreated with liquiritigenin （0.02, 0.2, and 2 pmol/L） prior to Aβ25-35 exposure. Following treatment, viability of the cells was measured by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide analysis and by a lactate dehydrogenase activity-based cytotoxicity assay. Intracellular Ca^2＋ concentration （Ca^2＋]i） and levels of reactive oxygen species （ROS）, as well as apoptotic rates, were determined. Our studies were extended in tests of whether liquiritigenin treatment could inhibit the secretion of Aβ1-40 as measured using an ELISA method. In order to analyze which genes may be involved, we used a microarray assay to compare gene expression patterns. Finally, the levels of specific proteins related to neurotrophy and neurodenegeration were detected by Western blotting.
Results： Pretreated neurons with liquiritigenin in the presence of Aβ25-35 increased cell viability in a concentration-dependent manner. Liquiritigenin treatment also attenuated Aβ25-35-induced increases in Ca^2＋]i and ROS level and decreased the apoptotic rate of neurons. Some genes, including B-cell lymphoma/leukemia-2 （Bcl-2）, neurotrophin 3 （Ntf-3） and amyloid 3 （A4） precursor protein-binding, family B, member 1 （Apbb-1） were regulated by liquiritigenin; similar results were shown at the protein level by Western blotting.
Conclusion： Our results demonstrate that liquiritigenin exhibits neuroprotective effects against Aβ25-35-induced neurotoxicity and that it can decrease the secretion of Aβ1-40. Therefore, liquiritigenin may be useful for further study as a prodrug for treatment of Alzheimer＇s disease.

Liquiritigenin inhibits Aβ25-35-induced neurotoxicity and secretion of Aβ1-40 in rat hippocampal neurons

liquiritigenin selective ERβ agonist neuroprotection Aβ secretion