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 μmol/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 Ca2+ concentration ([Ca2+]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 [Ca2+]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 β (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.
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