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A Novel Multifunctional Compound Camellikaempferoside B Decreases A beta Production, Interferes with A beta Aggregation, and Prohibits A beta-Mediated Neurotoxicity and Neuroinflammation
Yang, Shigao1; Liu, Wen1,3; Lu, Shuai1; Tian, Yong-zhen2; Wang, Wei-yun3; Ling, Tie-jun2; Liu, Rui-tian1
2016-04-01
发表期刊ACS CHEMICAL NEUROSCIENCE
ISSN1948-7193
卷号7期号:4页码:505-518
摘要Accumulating evidence suggested that soluble oligomeric beta-amyloid protein (A beta) 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 A beta production by decreasing beta-secretase activity. Moreover, YCF-2 suppressed A beta 42 fibrillation and facilitated nontoxic oligomer formation by binding to A beta 42 oligomers and by blocking the conformational transition to beta-sheet. Furthermore, YCF-2 ameliorated A beta-induced neuronal cell death, ROS production, inflammatory factor release, and microglia activation by blocking the NF-kappa B signaling pathway in microglia. These findings indicated that YCF-2 with a novel lead structure has potential applications for drug development for AD treatment.
关键词Amyloid-beta Camellikaempferoside b Beta-secretase Aggregation Neurotoxicity Microglia
文章类型Article
WOS标题词Science & Technology ; Life Sciences & Biomedicine
DOI10.1021/acschemneuro.6b00091
收录类别SCI
语种英语
关键词[WOS]NF-KAPPA-B ; AMYLOID PRECURSOR PROTEIN ; DISEASE TRANSGENIC MICE ; RESCUES MEMORY DEFICITS ; P-COUMARIC ACID ; ALZHEIMERS-DISEASE ; OXIDATIVE STRESS ; NEURONAL APOPTOSIS ; QUERCETIN PROTECTS ; FIBRIL FORMATION
WOS研究方向Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Neurosciences & Neurology
WOS类目Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Neurosciences
项目资助者National Natural Science Foundation of China(81371208 ; National Science and Technology Major Projects of New Drugs(2012ZX09103301-001 ; 81171014 ; 2014ZX09102045-006) ; 31471720)
WOS记录号WOS:000374812300013
引用统计
被引频次:11[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.ipe.ac.cn/handle/122111/21032
专题生化工程国家重点实验室
作者单位1.Chinese Acad Sci, Inst Proc Engn, Natl Key Lab Biochem Engn, Beijing 100190, Peoples R China
2.Anhui Agr Univ, State Key Lab Tea Plant Biol & Utilizat, 130 West Changjiang Rd, Hefei 230036, Peoples R China
3.Anhui Agr Univ, Sch Life Sci, Hefei 230036, Peoples R China
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Yang, Shigao,Liu, Wen,Lu, Shuai,et al. A Novel Multifunctional Compound Camellikaempferoside B Decreases A beta Production, Interferes with A beta Aggregation, and Prohibits A beta-Mediated Neurotoxicity and Neuroinflammation[J]. ACS CHEMICAL NEUROSCIENCE,2016,7(4):505-518.
APA Yang, Shigao.,Liu, Wen.,Lu, Shuai.,Tian, Yong-zhen.,Wang, Wei-yun.,...&Liu, Rui-tian.(2016).A Novel Multifunctional Compound Camellikaempferoside B Decreases A beta Production, Interferes with A beta Aggregation, and Prohibits A beta-Mediated Neurotoxicity and Neuroinflammation.ACS CHEMICAL NEUROSCIENCE,7(4),505-518.
MLA Yang, Shigao,et al."A Novel Multifunctional Compound Camellikaempferoside B Decreases A beta Production, Interferes with A beta Aggregation, and Prohibits A beta-Mediated Neurotoxicity and Neuroinflammation".ACS CHEMICAL NEUROSCIENCE 7.4(2016):505-518.
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