PMID- 29519323
OWN - NLM
STAT- MEDLINE
DCOM- 20180809
LR  - 20180809
IS  - 1618-095X (Electronic)
IS  - 0944-7113 (Linking)
VI  - 41
DP  - 2018 Mar 1
TI  - Icariside II ameliorates ibotenic acid-induced cognitive impairment and apoptotic 
      response via modulation of MAPK pathway in rats.
PG  - 74-81
LID - S0944-7113(18)30021-7 [pii]
LID - 10.1016/j.phymed.2018.01.025 [doi]
AB  - BACKGROUND: Excitotoxicity is extensively recognized as a major pathological 
      process of neuronal death and has been proved to play a key role in Alzheimer's 
      disease (AD). ICS II, a flavonoid compound from Herba Epimedii Maxim, is 
      attracting great interests due to its neuroprotective properties. PURPOSE: The 
      present study was aimed to explore the effects of ICS II on cognitive dysfunction 
      and apoptotic response induced by excitatory neurotoxin ibotenic acid (IBO) 
      injection in rats. METHODS: Rats subjected to bilateral hippocampal injection of 
      IBO were intragastrically administered with 4, 8 and 16 mg/kg ICS II or 0.6 mg/kg 
      donepezil once a day for continuous 20 days. Learning and memory functions were 
      tested by Morris water maze. The neuronal morphology in hippocampus was examined 
      by HE staining and Nissl staining, respectively. Neuronal apoptosis was detected 
      by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) 
      assay. The expression of apoptosis-related proteins and the activation of 
      mitogen-activated protein kinase (MAPK) pathway were detected by Western blot. 
      RESULTS: It was uncovered that hippocampal injection of IBO caused learning and 
      memory impairment, neuronal damage and loss, as well as pro-apoptotic response. 
      ICS II administrated at doses of 8 and 16 mg/kg not only rescued behavioral 
      performance, but also protected hippocampal neurons against neurotoxicity via 
      suppressing the elevation of Bax/Bcl-2 ratio and the activation of caspase-3. 
      Meanwhile, ICS II repressed the down-regulation of calbindin protein induced by 
      IBO. Additionally, ICS II exerted an inhibitory effect on MAPK (p38, ERK1/2 and 
      JNK) pathway phosphorylation. CONCLUSION: These results suggest that ICS II 
      attenuates IBO-induced cognitive deficits, possibly via the regulation of 
      calbindin expression and the inhibition of apoptotic response. In addition, the 
      MAPK signaling pathway is implicated in the potential mechanisms of ICS II 
      against IBO-induced excitotoxicity, indicating that ICS II is a promising 
      compound for treatment of excitotoxicity-related diseases, including AD.
CI  - Copyright (c) 2018 Elsevier GmbH. All rights reserved.
FAU - He, Lianzi
AU  - He L
AD  - Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical 
      University, Zunyi, Guizhou 563000, China; Joint International Research Laboratory 
      of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 
      Guizhou 563003, China.
FAU - Deng, Yuanyuan
AU  - Deng Y
AD  - Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical 
      University, Zunyi, Guizhou 563000, China; Joint International Research Laboratory 
      of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 
      Guizhou 563003, China.
FAU - Gao, Jianmei
AU  - Gao J
AD  - School of Pharmacy, Zunyi Medical University, Zunyi, Guizhou 563003, China.
FAU - Zeng, Lingrong
AU  - Zeng L
AD  - Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical 
      University, Zunyi, Guizhou 563000, China; Joint International Research Laboratory 
      of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 
      Guizhou 563003, China.
FAU - Gong, Qihai
AU  - Gong Q
AD  - Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical 
      University, Zunyi, Guizhou 563000, China; Joint International Research Laboratory 
      of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, 
      Guizhou 563003, China. Electronic address: gqh@zmc.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20180131
PL  - Germany
TA  - Phytomedicine
JT  - Phytomedicine : international journal of phytotherapy and phytopharmacology
JID - 9438794
RN  - 0 (Calbindins)
RN  - 0 (Flavonoids)
RN  - 113558-15-9 (baohuoside I)
RN  - 2552-55-8 (Ibotenic Acid)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Alzheimer Disease/chemically induced/drug therapy/metabolism
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Calbindins/metabolism
MH  - Caspase 3/metabolism
MH  - Cognitive Dysfunction/chemically induced/*drug therapy/metabolism
MH  - Down-Regulation
MH  - Flavonoids/*pharmacology
MH  - Hippocampus/drug effects/pathology
MH  - Ibotenic Acid/toxicity
MH  - MAP Kinase Signaling System/*drug effects
MH  - Male
MH  - Maze Learning/drug effects
MH  - Memory Disorders/drug therapy/metabolism
MH  - Neurons/drug effects/pathology
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Apoptosis
OT  - Excitotoxicity
OT  - Ibotenic acid
OT  - Icariside II
EDAT- 2018/03/10 06:00
MHDA- 2018/08/10 06:00
CRDT- 2018/03/10 06:00
PHST- 2017/10/02 00:00 [received]
PHST- 2017/12/12 00:00 [revised]
PHST- 2018/01/23 00:00 [accepted]
PHST- 2018/03/10 06:00 [entrez]
PHST- 2018/03/10 06:00 [pubmed]
PHST- 2018/08/10 06:00 [medline]
AID - S0944-7113(18)30021-7 [pii]
AID - 10.1016/j.phymed.2018.01.025 [doi]
PST - ppublish
SO  - Phytomedicine. 2018 Mar 1;41:74-81. doi: 10.1016/j.phymed.2018.01.025. Epub 2018 
      Jan 31.