Liquiritigenin inhibits Abeta(25-35)-induced neurotoxicity and secretion of Abeta(1-40) in rat hippocampal neurons.

Abstract

AIM:

To examine whether liquiritigenin, a newly found agonist of selective estrogen receptor-beta, has neuroprotective activity against beta-amyloid peptide (Abeta) in rat hippocampal neurons.

METHODS:

Primary cultures of rat hippocampal neurons were pretreated with liquiritigenin (0.02, 0.2, and 2 micromol/L) prior to Abeta(25-35) 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 Abeta(1-40) 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 Abeta(25-35) increased cell viability in a concentration-dependent manner. Liquiritigenin treatment also attenuated Abeta(25-35)-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 beta (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 Abeta(25-35)-induced neurotoxicity and that it can decrease the secretion of Abeta(1-40). Therefore, liquiritigenin may be useful for further study as a prodrug for treatment of Alzheimer's disease.Acta Pharmacologica Sinica (2009) 30: 899-906; doi: 10.1038/aps.2009.74.

• Authors: Rui-Ting Liu, Li-Bo Zou, Qiu-Jun Lü
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 30 Issue 7 Pg. 899-906 (Jul 2009) ISSN: 1745-7254 [Electronic] United States
• PMID: 19574995 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Flavanones
• Neuroprotective Agents
• Peptide Fragments
• Reactive Oxygen Species
• amyloid beta-protein (1-40)
• amyloid beta-protein (25-35)
• Calcium
• liquiritigenin

Topics

• Amyloid beta-Peptides (metabolism, toxicity)
• Animals
• Calcium (metabolism)
• Cell Membrane Permeability (drug effects)
• Cells, Cultured
• Flavanones (chemistry, pharmacology)
• Gene Expression (drug effects)
• Gene Expression Profiling
• Hippocampus (cytology)
• Molecular Structure
• Neurons (cytology, drug effects, metabolism)
• Neuroprotective Agents (chemistry, pharmacology)
• Oligonucleotide Array Sequence Analysis
• Peptide Fragments (metabolism, toxicity)
• Rats
• Rats, Wistar
• Reactive Oxygen Species (metabolism)