PMID- 24468471
OWN - NLM
STAT- MEDLINE
DCOM- 20141125
LR  - 20171116
IS  - 1558-1497 (Electronic)
IS  - 0197-4580 (Linking)
VI  - 35
IP  - 6
DP  - 2014 Jun
TI  - Pinocembrin improves cognition and protects the neurovascular unit in Alzheimer 
      related deficits.
PG  - 1275-85
LID - S0197-4580(13)00673-8 [pii]
LID - 10.1016/j.neurobiolaging.2013.12.031 [doi]
AB  - Amyloid-beta (Abeta) peptides accumulate in the brain and initiate a cascade of 
      pathologic events in Alzheimer's disease. The receptor for advanced glycation end 
      products (RAGE) has been implicated to mediate Abeta-induced perturbations in the 
      neurovascular unit (NVU). We demonstrated that pinocembrin exhibits 
      neuroprotection through inhibition of the Abeta and/or RAGE pathway, but the 
      therapeutic role and mechanism involved are not ascertained. Here, we report that 
      a 3-month treatment with pinocembrin prevents the cognition decline in APP/PS1 
      transgenic mice without altering Abeta burden and oxidative stress. Instead, 
      pinocembrin is effective in conferring neurovascular protection through 
      maintenance of neuropil ultrastructure, reduction of glial activation and levels 
      of inflammatory mediators, preservation of microvascular function, improving the 
      cholinergic system by conserving the ERK-CREB-BDNF pathway, and modulation of 
      RAGE-mediated transduction. Furthermore, in an in vitro model, pinocembrin 
      provides the NVU protection against fibrillar Abeta(1)(-)(4)(2), accompanied by regulation 
      of neurovascular RAGE pathways. Our findings indicate that pinocembrin improves 
      cognition, at least in part, attributable to the NVU protection, and highlights 
      pinocembrin as a potential therapeutic strategy for the prevention and/or 
      treatment of Alzheimer's disease.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Liu, Rui
AU  - Liu R
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China.
FAU - Li, Jin-ze
AU  - Li JZ
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China.
FAU - Song, Jun-ke
AU  - Song JK
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China.
FAU - Zhou, Dan
AU  - Zhou D
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China.
FAU - Huang, Chao
AU  - Huang C
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China.
FAU - Bai, Xiao-yu
AU  - Bai XY
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China.
FAU - Xie, Tao
AU  - Xie T
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China.
FAU - Zhang, Xue
AU  - Zhang X
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China.
FAU - Li, Yong-jie
AU  - Li YJ
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China.
FAU - Wu, Cai-xia
AU  - Wu CX
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China; School of Life Science and 
      Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang 110016, China.
FAU - Zhang, Lan
AU  - Zhang L
AD  - Key Laboratory for Neurodegenerative Diseases of Ministry of Education, 
      Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 
      Beijing Geriatric Medical Research Center, Beijing 100053, PR China.
FAU - Li, Lin
AU  - Li L
AD  - Key Laboratory for Neurodegenerative Diseases of Ministry of Education, 
      Department of Pharmacology, Xuanwu Hospital of Capital Medical University, 
      Beijing Geriatric Medical Research Center, Beijing 100053, PR China.
FAU - Zhang, Tian-tai
AU  - Zhang TT
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China. Electronic address: 
      ttzhang@imm.ac.cn.
FAU - Du, Guan-hua
AU  - Du GH
AD  - State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 
      Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union 
      Medical College, Beijing 100050, P. R. China. Electronic address: 
      bessie0420@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131228
PL  - United States
TA  - Neurobiol Aging
JT  - Neurobiology of aging
JID - 8100437
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Flavanones)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptor for Advanced Glycation End Products)
RN  - 0 (Receptors, Immunologic)
RN  - 8T7C8CH791 (pinocembrin)
SB  - IM
MH  - Alzheimer Disease/*drug therapy/metabolism/pathology/*psychology
MH  - Amyloid beta-Peptides/metabolism
MH  - Animals
MH  - Brain/metabolism
MH  - Brain-Derived Neurotrophic Factor/physiology
MH  - Cognition/*drug effects
MH  - Cyclic AMP Response Element-Binding Protein/physiology
MH  - Disease Models, Animal
MH  - Female
MH  - Flavanones/*pharmacology/*therapeutic use
MH  - MAP Kinase Signaling System/physiology
MH  - Male
MH  - Mice
MH  - *Neuroprotective Agents
MH  - Receptor for Advanced Glycation End Products
MH  - Receptors, Immunologic/physiology
MH  - Signal Transduction/drug effects
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Amyloid-beta peptide
OT  - Pinocembrin
OT  - The neurovascular unit
OT  - The receptor for advanced glycation end products
EDAT- 2014/01/29 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/01/29 06:00
PHST- 2013/05/14 00:00 [received]
PHST- 2013/11/13 00:00 [revised]
PHST- 2013/12/25 00:00 [accepted]
PHST- 2014/01/29 06:00 [entrez]
PHST- 2014/01/29 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S0197-4580(13)00673-8 [pii]
AID - 10.1016/j.neurobiolaging.2013.12.031 [doi]
PST - ppublish
SO  - Neurobiol Aging. 2014 Jun;35(6):1275-85. doi: 
      10.1016/j.neurobiolaging.2013.12.031. Epub 2013 Dec 28.