title: An Improved Drugs Screening System Reveals that Baicalein Ameliorates the Aβ/AMPA/NMDA-Induced Depolarization of Neurons.
abstract: The presence of amyloid-β (Aβ) plaque and tau protein hyperphosphorylation in brain tissue is the pathological hallmark of Alzheimer's disease (AD). At least some Aβ neurotoxicity is caused by the presence of excess glutamate that has been induced by Aβ accumulation. Memantine is currently the only NMDA receptor inhibitor approved for treating moderate-to-severe AD patients. We utilized primary cortical neurons and DiBAC4(3), a slow-response voltage sensitive fluorescence dye, to create a novel system for screening herbal medicines that allows the identification of pure compounds able to ameliorate Aβ-induced abnormal depolarization. The intensity of DiBAC4(3) fluorescence was increased when primary neurons were stimulated by Aβ; furthermore, pre-treatment with memantine abolished this change. Using this system, we identified six crude extracts made from herbal medicines that effectively alleviated this Aβ-induced abnormal depolarization. Among these herbal medicines, one pure compound, baicalein, which was known to be present in Scutellaria baricalensis and is known to improve memory using an AD mouse model, was identified by our assay. However, the compound's molecular mechanism remained unknown. We found that baicalein, in addition to inhibiting Aβ-induced depolarization, possibly functions as an antagonist of AMPA and NMDA receptors. Taken together, we have established a system/platform to identify herbal medicines that ameliorate Aβ-induced depolarization of neurons. Equally important, baicalein is a candidate drug with great potential for the treatment of AD patients.
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Tian-Syuan
authors.initials: TS
authors.lastname: Lin
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Tsai
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Chih-Han
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: Song
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Rih-Sheng
authors.initials: RS
authors.lastname: Huang
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Hsiu-Mei
authors.initials: HM
authors.lastname: Hsieh-Li
authors.affiliation: Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan.
authors.forename: Mei-Chih
authors.initials: MC
authors.lastname: Liang
authors.affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan.
authors.forename: Yenshou
authors.initials: Y
authors.lastname: Lin
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D044950:Flavanones / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000633:toxicity; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D044950:Flavanones; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D010936:Plant Extracts; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C075222:amyloid beta-protein (1-42); C006680:baicalein; D048670:MAP Kinase Kinase 4
keywords: Alzheimer’s disease; DiBAC4(3); amyloid-β; baicalein; glutamate receptors; memantine