title: Traditional Chinese Nootropic Medicine Radix Polygalae and Its Active Constituent Onjisaponin B Reduce β-Amyloid Production and Improve Cognitive Impairments.
abstract: Decline of cognitive function is the hallmark of Alzheimer's disease (AD), regardless of the pathological mechanism. Traditional Chinese medicine has been used to combat cognitive impairments and has been shown to improve learning and memory. Radix Polygalae (RAPO) is a typical and widely used herbal medicine. In this study, we aimed to follow the β-amyloid (Aβ) reduction activity to identify active constituent(s) of RAPO. We found that Onjisaponin B of RAPO functioned as RAPO to suppress Aβ production without direct inhibition of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) and γ-secretase activities. Our mechanistic study showed that Onjisaponin B promoted the degradation of amyloid precursor protein (APP). Further, oral administration of Onjisaponin B ameliorated Aβ pathology and behavioral defects in APP/PS1 mice. Taken together, our results indicate that Onjisaponin B is effective against AD, providing a new therapeutic agent for further drug discovery.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Cui
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Hou
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Qin
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Graduate School, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Cun
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou, China.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|Translational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.|School of Life Science and Technology, Collaborative Innovation Center for Brain Science, Tongji University, Shanghai, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Pei
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000096:biosynthesis*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002460:Cell Line; D003072:Cognition Disorders / Q000188:drug therapy / Q000378:metabolism*; D004195:Disease Models, Animal; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008516:Medicine, Chinese Traditional; D051379:Mice; D008822:Mice, Transgenic; D018697:Nootropic Agents / Q000494:pharmacology*; D059748:Proteolysis / Q000187:drug effects; D012503:Saponins / Q000494:pharmacology*; D013379:Substrate Specificity; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D018697:Nootropic Agents; D012503:Saponins; D014315:Triterpenes; C474233:onjisaponin B; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse