Effects of liquiritigenin treatment on the learning and memory deficits induced by amyloid beta-peptide (25-35) in rats.

Considerable evidence has emerged supporting the neuroprotective and cognition-preserving effects of estrogen, but these benefits are complicated by the evidence that estrogen increases the risk of certain cancers. Selective estrogen receptor modulators (SERMs) that specifically target the brain while avoiding peripheral organs offer a way to allow the application of estrogen treatment to neurodegenerative diseases with fewer undesirable effects. In an attempt to find such estrogen substitutes, liquiritigenin was discovered as a relatively selective estrogen receptor beta (ERbeta) agonist. In the present study, we extend our previous findings to investigate the effects of liquiritigenin on the learning and memory deficits and related neuropathology in Abeta(25-35) hippocampal-injected rats. Our results show that liquiritigenin treatment improves the behavioral performance of the model rats and attenuates neuronal loss in the brain. More importantly, liquiritigenin treatment decreases mRNA levels and protein expression of Notch-2, an effect that could promote the generation of new neurons. These findings provide evidence for the beneficial activity of liquiritigenin in a brain-injured rat model and support the continued investigation of SERMs such as liquiritigenin as an alternative to estrogen-based hormone therapy in reducing the risk of neurodegenerative diseases such as Alzheimer's disease.