PMID- 31612304
OWN - NLM
STAT- MEDLINE
DCOM- 20200330
LR  - 20200330
IS  - 1573-6903 (Electronic)
IS  - 0364-3190 (Linking)
VI  - 44
IP  - 12
DP  - 2019 Dec
TI  - Icariin Ameliorates Amyloid Pathologies by Maintaining Homeostasis of Autophagic 
      Systems in Abeta(1-42)-Injected Rats.
PG  - 2708-2722
LID - 10.1007/s11064-019-02889-z [doi]
AB  - Macroautophagy, a sole pathway for dysfunctional organelles or aggregated 
      proteins turnover, has been implicated in the early development of Alzheimer's 
      disease (AD). Previous studies have found that reversal of autophagy dysfunction 
      in APP transgenic mice ameliorates amyloid pathologies. Icariin (ICA), the main 
      component from traditional Chinese herb Epimedium brevicornu Maxim., can reduce 
      accumulations of amyloid-beta (Abeta) peptide in vivo and in vitro, but the mechanism 
      remains unclear. Here, we explored the effects of ICA on autophagy-lysosomal 
      pathway in intracerebroventricular (icv) injection of human Abeta(1-42) peptide 
      rats. We demonstrated that feeding the rats with ICA (30 mg/kg, 60 mg/kg and 
      90 mg/kg rat, per os) for 4 weeks rescued the Abeta(1-42)-induced spatial memory 
      impairments, reduced endogenous rat Abeta(42) tested by ELISA and decreased Abeta 
      accumulation using 6E10 antibody. Furthermore, Abeta(1-42) induced strong autophagy 
      response, however ICA decreased the levels of microtubule-associated protein 1 
      light chain 3 (LC3) II/LC3I, Beclin1, Cathepsin D (Cat D) and brain lysosomal 
      Cathepsin D activity. We also observed that ICA enhanced the phosphorylation of 
      protein kinase B (PKB/AKT) and p70 ribosomal protein S6 kinase (p70S6K). In 
      addition, ICA arrested Abeta(1-42)-induced cells loss, mitochondrias damage, nuclear 
      membranes unclear and abundant nucleas chromatin agglutinates in hippocampus, 
      lessened the expression of Cleaved-caspase-3, brain oxidative stress, astroglial 
      activation. These findings suggest that ICA can ameliorate amyloid pathologies 
      with improving autophagy-lysosome function and Chinese materia medica may be 
      potential for AD treatment.
FAU - Jiang, Xia
AU  - Jiang X
AD  - Department of Pathology, Hubei University of Chinese Medicine, Wuhan, 430065, 
      People's Republic of China. jane_j_09@126.com.
AD  - New products of TCM senile Diseases Co-innovation Center of Hubei, Wuhan, 430065, 
      People's Republic of China. jane_j_09@126.com.
FAU - Chen, Lin-Lin
AU  - Chen LL
AD  - New products of TCM senile Diseases Co-innovation Center of Hubei, Wuhan, 430065, 
      People's Republic of China.
FAU - Lan, Zhou
AU  - Lan Z
AD  - New products of TCM senile Diseases Co-innovation Center of Hubei, Wuhan, 430065, 
      People's Republic of China.
FAU - Xiong, Fan
AU  - Xiong F
AD  - Department of Pathology, Hubei University of Chinese Medicine, Wuhan, 430065, 
      People's Republic of China.
FAU - Xu, Xiang
AU  - Xu X
AD  - Department of Pathology, Hubei University of Chinese Medicine, Wuhan, 430065, 
      People's Republic of China.
FAU - Yin, Yang-Yang
AU  - Yin YY
AD  - Department of Pathology, Hubei University of Chinese Medicine, Wuhan, 430065, 
      People's Republic of China.
FAU - Li, Ping
AU  - Li P
AD  - Department of Pathology, Hubei University of Chinese Medicine, Wuhan, 430065, 
      People's Republic of China.
FAU - Wang, Ping
AU  - Wang P
AD  - New products of TCM senile Diseases Co-innovation Center of Hubei, Wuhan, 430065, 
      People's Republic of China. pwang54@aliyun.com.
LA  - eng
GR  - 81303252/National Natural Science Foundation of China/
GR  - 81573865/National Natural Science Foundation of China/
GR  - 2017CFB733/Natural Science Foundation of Hubei Province/
GR  - 2016T90685/Postdoctoral Research Foundation of China/
PT  - Journal Article
DEP - 20191015
PL  - United States
TA  - Neurochem Res
JT  - Neurochemical research
JID - 7613461
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Flavonoids)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peptide Fragments)
RN  - 0 (amyloid beta-protein (1-42))
RN  - VNM47R2QSQ (icariin)
SB  - IM
MH  - Alzheimer Disease/chemically induced/*drug therapy
MH  - Amyloid beta-Peptides/administration & dosage
MH  - Animals
MH  - Flavonoids/*therapeutic use
MH  - Hippocampus/metabolism/pathology
MH  - Homeostasis/*drug effects
MH  - Humans
MH  - Injections
MH  - Lysosomes/drug effects
MH  - Macroautophagy/*drug effects
MH  - Male
MH  - Maze Learning/drug effects
MH  - Neuroprotective Agents/*therapeutic use
MH  - Peptide Fragments/administration & dosage
MH  - Rats, Sprague-Dawley
MH  - Spatial Memory/drug effects
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Autophagy
OT  - Abeta
OT  - Memory deficit
OT  - Protein aggregation
EDAT- 2019/10/16 06:00
MHDA- 2020/03/31 06:00
CRDT- 2019/10/16 06:00
PHST- 2019/03/30 00:00 [received]
PHST- 2019/10/03 00:00 [accepted]
PHST- 2019/09/26 00:00 [revised]
PHST- 2019/10/16 06:00 [pubmed]
PHST- 2020/03/31 06:00 [medline]
PHST- 2019/10/16 06:00 [entrez]
AID - 10.1007/s11064-019-02889-z [pii]
AID - 10.1007/s11064-019-02889-z [doi]
PST - ppublish
SO  - Neurochem Res. 2019 Dec;44(12):2708-2722. doi: 10.1007/s11064-019-02889-z. Epub 
      2019 Oct 15.