title: Effects and possible mechanisms of action of acacetin on the behavior and eye morphology of Drosophila models of Alzheimer's disease.
abstract: The human β-amyloid (Aβ) cleaving enzyme (BACE-1) is a target for Alzheimer's disease (AD) treatments. This study was conducted to determine if acacetin extracted from the whole Agastache rugosa plant had anti-BACE-1 and behavioral activities in Drosophila melanogaster AD models and to determine acacetin's mechanism of action. Acacetin (100, 300, and 500 μM) rescued amyloid precursor protein (APP)/BACE1-expressing flies and kept them from developing both eye morphology (dark deposits, ommatidial collapse and fusion, and the absence of ommatidial bristles) and behavioral (motor abnormalities) defects. The reverse transcription polymerase chain reaction analysis revealed that acacetin reduced both the human APP and BACE-1 mRNA levels in the transgenic flies, suggesting that it plays an important role in the transcriptional regulation of human BACE-1 and APP. Western blot analysis revealed that acacetin reduced Aβ production by interfering with BACE-1 activity and APP synthesis, resulting in a decrease in the levels of the APP carboxy-terminal fragments and the APP intracellular domain. Therefore, the protective effect of acacetin on Aβ production is mediated by transcriptional regulation of BACE-1 and APP, resulting in decreased APP protein expression and BACE-1 activity. Acacetin also inhibited APP synthesis, resulting in a decrease in the number of amyloid plaques.
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Xue
authors.initials: X
authors.lastname: Wang
authors.affiliation: Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Haribalan
authors.initials: H
authors.lastname: Perumalsamy
authors.affiliation: Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-921, Republic of Korea.
authors.forename: Hyung Wook
authors.initials: HW
authors.lastname: Kwon
authors.affiliation: R&D Coordination Division, Rural Development Administration, Jeonju 560-500, Republic of Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Na
authors.affiliation: Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea.|College of Plant Science &Technology, Huazhong Agricultural University, Wuhan 430070, Hubei, P.R. China.
authors.forename: Young-Joon
authors.initials: YJ
authors.lastname: Ahn
mesh_terms: D031327:Agastache / Q000737:chemistry / Q000378:metabolism; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D004330:Drosophila / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005123:Eye / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology*; D031541:Fluorescence Resonance Energy Transfer; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008136:Longevity / Q000187:drug effects; D008297:Male; D009828:Oleanolic Acid / Q000737:chemistry / Q000494:pharmacology / Q000031:analogs & derivatives; D010641:Phenotype; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D047309:Flavones; D014315:Triterpenes; D009828:Oleanolic Acid; C412811:maslinic acid; D053829:Amyloid Precursor Protein Secretases; C023717:acacetin