title: Phenylpropanoids from cinnamon bark reduced β-amyloid production by the inhibition of β-secretase in Chinese hamster ovarian cells stably expressing amyloid precursor protein.
abstract: β-Amyloid (Aβ) is a substance of Alzheimer disease (AD), which is generated via the amyloidogenic pathway from amyloid precursor protein (APP) by β-secretase and γ-secretase. Inhibition of Aβ production is a potential therapeutic approach to AD. Thus, we tested the hypothesis that cinnamon bark (Cinnamomi Cortex Spissus), the dried bark of Cinnamomum cassia Blume (Lauraceae), and its constituents are beneficial to AD. The methanol extract of cinnamon bark efficiently reduced Aβ40 production in Chinese hamster ovarian (CHO) cells stably expressing APP as determined by enzyme-linked immunosorbent assay. Bioassay-guided isolation of cinnamon bark extract was carried out using open column chromatography and high-performance liquid chromatography, and the following 6 phenylpropanoids were isolated: syringaresinol (1); medioresinol (2); coumarin (3); 2-hydroxycinnamaldehyde (4); cryptamygin A (5); and 3',5,7-trimethoxy epicatechin (6). Among these, 4 μg/mL medioresinol and cryptamygin A reduced Aβ40 production by 50% and 60%, respectively, compared with dimethyl sulfoxide-treated control cells. The IC50values of medioresinol and cryptamygin A for the inhibition of Aβ40 production were 10.8 and 8.2 μg/mL, respectively. Furthermore, treatment of APP-CHO cells with either compound decreased the amount of β-secretase and sAPPβ (the proteolytic fragment of APP catalyzed by β-secretase). These results suggest that the antiamyloidogenic activity of cinnamon bark extract was exerted by medioresinol and cryptamygin A via a reduction in the amount of β-secretase. The extract of cinnamon bark contains potentially valuable antiamyloidogenic agents for the prevention and treatment of AD.
authors.affiliation: World Class University, Department of Nanomedicine, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Yu Jeong
authors.initials: YJ
authors.lastname: Kang
authors.affiliation: Laboratory of Pharmacognosy, College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea.
authors.forename: Dae-Gun
authors.initials: DG
authors.lastname: Seo
authors.affiliation: World Class University, Department of Nanomedicine, Dankook University, Cheonan 330-714, Republic of Korea; Laboratory of Pharmacognosy, College of Pharmacy, Dankook University, Cheonan 330-714, Republic of Korea. Electronic address: soypark23@dankook.ac.kr.
authors.forename: So-Young
authors.initials: SY
authors.lastname: Park
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002935:Cinnamomum zeylanicum / Q000737:chemistry*; D006224:Cricetinae; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D017705:Lignans / Q000494:pharmacology; D024301:Plant Bark / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology*; D018547:Plant Stems / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D004791:Enzyme Inhibitors; D017705:Lignans; D010936:Plant Extracts; C576388:medioresinol; D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer disease; Cinnamomum cassia; Cryptamygin A; Medioresinol; β-Amyloid; β-Secretase