期刊
ACTA PHARMACOLOGICA SINICA
卷 30, 期 7, 页码 899-906出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/aps.2009.74
关键词
liquiritigenin; selective ER beta agonist; neuroprotection; A beta secretion
资金
- Academy of Military Medical Science and Genova (Beijing) Biopharmaceutical Research Institute
Aim: To examine whether liquiritigenin, a newly found agonist of selective estrogen receptor-beta, has neuroprotective activity against beta-amyloid peptide (A beta) in rat hippocampal neurons. Methods: Primary cultures of rat hippocampal neurons were pretreated with liquiritigenin (0.02, 0.2, and 2 mu mol/L) prior to A beta(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 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 A beta(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 A beta(25-35) increased cell viability in a concentration-dependent manner. Liquiritigenin treatment also attenuated A beta(25-35)-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 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 A beta(25-35)-induced neurotoxicity and that it can decrease the secretion of A beta(1-40). Therefore, liquiritigenin may be useful for further study as a prodrug for treatment of Alzheimer's disease.
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