PMID- 28847282
OWN - NLM
STAT- MEDLINE
DCOM- 20190304
LR  - 20211204
IS  - 1875-5828 (Electronic)
IS  - 1567-2050 (Linking)
VI  - 15
IP  - 1
DP  - 2018
TI  - Ginkgo biloba Extract EGb761 Attenuates Hyperhomocysteinemia-induced AD Like Tau 
      Hyperphosphorylation and Cognitive Impairment in Rats.
PG  - 89-99
LID - 10.2174/1567205014666170829102135 [doi]
AB  - BACKGROUND: Ginkgo biloba extract EGb761 has shown the neuroprotective effects on 
      Alzheimer's disease (AD) through the protection against the Abeta-induced 
      neurotoxicity. However, it is not completedly clear whether EGb761 attenuates tau 
      hyperphosphorylation, another of the most prominent mechanisms underlying the 
      pathology of AD. METHODS: we employed hyperhomocysteinemia (HHcy) to mimic AD 
      like pathological alterations and memory deficits in rats as model, and injected 
      EGb761 with or after HHcy injection as prevention and treatment, injected saline 
      as control. We measured the status of oxidative damage and spatial and learning 
      memory in rats. Then we detected the level of memory-related proteins, tau 
      phosphorylation and the level and activity of tau kinase (GSK-3beta) and phosphatase 
      (PP2A) by Western blotting and Immunohistochemistry. RESULTS: We found that 
      EGb761 could significantly antagonize HHcy-induced oxidative damage, recover 
      PP2Ac and GSK3beta activities deregulated by HHcy. Furthermore, tau was 
      hyperphosphorylated at Thr231, Ser262, Ser396, and Ser404, most common PP2Ac and 
      GSK3beta targeted sites in the hippocampus and prefrontal cortex of HHcy rats, 
      whereas EGb761 recovered the tau phosphorylation at those sites. Behavioral tests 
      revealed that EGb761 rescued HHcy-induced spatial reference memory deficit and 
      upregulated the expression of synapse-associated protein PSD95 and synapsin-1. 
      CONCLUSION: EGb761 might be a promising drug to treat AD through its 
      anti-oxidative activity and decreasing tau hyperphosphorylation besides the 
      protection against the Abeta-induced neurotoxicity.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.org.
FAU - Zeng, Kuan
AU  - Zeng K
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Li, Mengzhu
AU  - Li M
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Hu, Jichang
AU  - Hu J
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Mahaman, Yacoubou Abdoul Razak
AU  - Mahaman YAR
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Bao, Jian
AU  - Bao J
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Huang, Fang
AU  - Huang F
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Xia, Yiyuan
AU  - Xia Y
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Liu, Xinghua
AU  - Liu X
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Wang, Qun
AU  - Wang Q
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Wang, Jian-Zhi
AU  - Wang JZ
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Yang, Yang
AU  - Yang Y
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Liu, Rong
AU  - Liu R
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
FAU - Wang, Xiaochuan
AU  - Wang X
AD  - Department of Pathophysiology, School of Basic Medicine, Key Laboratory of 
      Ministry of Education of China for Neurological Disorders, Tongji Medical 
      College, Huazhong University of Science and Technology, Wuhan 430030. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United Arab Emirates
TA  - Curr Alzheimer Res
JT  - Current Alzheimer research
JID - 101208441
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, rat)
RN  - 0 (Mapt protein, rat)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nootropic Agents)
RN  - 0 (Plant Extracts)
RN  - 0 (Synapsins)
RN  - 0 (tau Proteins)
RN  - 19FUJ2C58T (Ginkgo biloba extract)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
SB  - IM
MH  - Alzheimer Disease/drug therapy/metabolism/pathology
MH  - Animals
MH  - Brain/drug effects/metabolism/pathology
MH  - Cognitive Dysfunction/*drug therapy/metabolism/pathology
MH  - Disease Models, Animal
MH  - Disks Large Homolog 4 Protein/metabolism
MH  - Ginkgo biloba
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - Hyperhomocysteinemia/*drug therapy/metabolism/pathology/psychology
MH  - Male
MH  - Memory/drug effects/physiology
MH  - Neuroprotective Agents/*pharmacology
MH  - Nootropic Agents/*pharmacology
MH  - Oxidative Stress/drug effects
MH  - Phosphorylation/drug effects
MH  - Plant Extracts/*pharmacology
MH  - Rats, Sprague-Dawley
MH  - Synapsins/metabolism
MH  - tau Proteins/*metabolism
OTO - NOTNLM
OT  - Alzheimer's disease (AD)
OT  - Ginkgo biloba extract EGb761
OT  - cognitive impairment
OT  - hyperhomocysteinemia (HHcy)
OT  - oxidative damage
OT  - tau hyperphosphorylation
EDAT- 2017/08/30 06:00
MHDA- 2019/03/05 06:00
CRDT- 2017/08/30 06:00
PHST- 2016/11/06 00:00 [received]
PHST- 2017/07/24 00:00 [revised]
PHST- 2017/08/04 00:00 [accepted]
PHST- 2017/08/30 06:00 [pubmed]
PHST- 2019/03/05 06:00 [medline]
PHST- 2017/08/30 06:00 [entrez]
AID - CAR-EPUB-85511 [pii]
AID - 10.2174/1567205014666170829102135 [doi]
PST - ppublish
SO  - Curr Alzheimer Res. 2018;15(1):89-99. doi: 10.2174/1567205014666170829102135.