Neuroprotective effects of liquiritigenin isolated from licorice roots on glutamate-induced apoptosis in hippocampal neuronal cells

• Liquiritigenin (LIQ) was isolated as an active compound from licorice roots.
• LIQ effectively reduced the early apoptosis in glutamate-treated HT22 cells.
• Ca2+ influx, ROS production, and lipid peroxidation were inhibited by LIQ.
• LIQ suppressed the mitochondrial stress and MAPKs phosphorylation.
• LIQ might be useful for the development of drugs for neurodegenerative disorders.

The progressive death of neurons following exposure to high concentrations of glutamate leads to loss of learning and memory and pathogenesis of neurodegenerative disorders. Therefore, identification of drugs that protect against glutamate-mediated neuronal cell death is a good strategy for prevention and treatment of neurodegenerative diseases. In this study, we isolated liquiritigenin, an active compound found in licorice roots, by column chromatography and examined its protective effects against glutamate-mediated apoptotic stimuli in a mouse hippocampus-derived neuronal cell line (HT22 cells). Cell viability was significantly recovered following treatment with 50 μM liquiritigenin up to 77.50 ± 1.93% over the control (100.00 ± 5.62%), whereas cell viability following 5 mM glutamate treatment was decreased to 52.52 ± 4.82%. Liquiritigenin effectively reduced glutamate-induced early apoptosis through inhibition of Ca2+ influx, intracellular reactive oxygen species (ROS) production, and lipid peroxidation. In addition, the levels of Bcl-2 and full-length Bid were protected, and that of mitochondrial Bax was reduced by liquiritigenin. Liquiritigenin suppressed not only the release of apoptosis-inducing factor (AIF), but also activation of mitogen-activated protein kinases (MAPKs) such as p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Therefore, the active component in licorice roots, liquiritigenin, might facilitate development of drug leads for neurodegenerative disorders.