title: Liquiritigenin inhibits Abeta(25-35)-induced neurotoxicity and secretion of Abeta(1-40) in rat hippocampal neurons.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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: Department of Pharmacology and Toxicology, Institute of Radiation Medicine, Academy of Military Medical Science, Beijing 100850, China.
authors: Rui-Ting
authors: RT
authors: Liu
authors: Li-Bo
authors: LB
authors: Zou
authors: Qiu-Jun
authors: QJ
authors: Lü
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000166:cytology*; D015394:Molecular Structure; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000378:metabolism* / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D044950:Flavanones; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); D002118:Calcium; C083152:liquiritigenin