The purpose of the present study was to determine if liquiritigenin, which is a newly discovered estrogen receptor beta (ERbeta) agonist, can induce differentiation of brain-derived progenitor cells from rats and to investigate the mechanisms involved. Treatment of brain-derived progenitor cell cultures with liquiritigenin increased the number of cells that differentiated into neurons; but the treatment did not alter the growth of astrocytes. Furthermore, treatment with liquiritigenin decreased Notch-2 mRNA and protein expression, which could promote the growth of new neurons. Using RNA interference (RNAi), we determined that inhibition of Notch-2 by liquiritigenin was probably ERbeta-dependent. These findings highlight the possible role of liquiritigenin in the repair and regeneration of injured brain tissue of patients with neurodegenerative diseases and support further investigation of the Notch-2 signaling pathway using ERbeta agonists.
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