title: A Novel Multifunctional Compound Camellikaempferoside B Decreases Aβ Production, Interferes with Aβ Aggregation, and Prohibits Aβ-Mediated Neurotoxicity and Neuroinflammation.
abstract: Accumulating evidence suggested that soluble oligomeric β-amyloid protein (Aβ) exerts diverse roles in neuronal cell death, neuroinflammation, oxidative stress, and the eventual dementia associated with Alzheimer's disease (AD). Developing an agent with multiple properties may be a reasonable strategy for the treatment of AD. In this study, we isolated a novel multifunctional compound named camellikaempferoside B (YCF-2) from Fuzhuan brick tea. YCF-2 consists of kaempferol backbone, p-coumaric acid (p-CA) group, and a novel structure of rhamnopyranosyl group at the C-4' position, possessing the properties of both kaempferol and p-CA. YCF-2 significantly inhibited Aβ production by decreasing β-secretase activity. Moreover, YCF-2 suppressed Aβ42 fibrillation and facilitated nontoxic oligomer formation by binding to Aβ42 oligomers and by blocking the conformational transition to β-sheet. Furthermore, YCF-2 ameliorated Aβ-induced neuronal cell death, ROS production, inflammatory factor release, and microglia activation by blocking the NF-κB signaling pathway in microglia. These findings indicated that YCF-2 with a novel lead structure has potential applications for drug development for AD treatment.
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing 100190, China.
authors.forename: Shigao
authors.initials: S
authors.lastname: Yang
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing 100190, China.|School of Life Science, Anhui Agricultural University , Hefei 230036, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing 100190, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University 130 West Changjiang Rd., Hefei 230036, P. R. China.
authors.forename: Yong-zhen
authors.initials: YZ
authors.lastname: Tian
authors.affiliation: School of Life Science, Anhui Agricultural University , Hefei 230036, China.
authors.forename: Wei-yun
authors.initials: WY
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University 130 West Changjiang Rd., Hefei 230036, P. R. China.
authors.forename: Tie-jun
authors.initials: TJ
authors.lastname: Ling
authors.affiliation: National Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences , Beijing 100190, China.
authors.forename: Rui-tian
authors.initials: RT
authors.lastname: Liu
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism*; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D006027:Glycosides / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D009457:Neuroglia / Q000187:drug effects / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010446:Peptide Fragments / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D006027:Glycosides; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C070688:camelliaside B; D011794:Quercetin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: Amyloid-beta; aggregation; camellikaempferoside B; microglia; neurotoxicity; β-secretase