PMID- 33277592
OWN - NLM
STAT- MEDLINE
DCOM- 20220128
LR  - 20230802
IS  - 1745-7254 (Electronic)
IS  - 1671-4083 (Print)
IS  - 1671-4083 (Linking)
VI  - 42
IP  - 9
DP  - 2021 Sep
TI  - Pseudoginsenoside-F11 attenuates cognitive dysfunction and tau phosphorylation in 
      sporadic Alzheimer's disease rat model.
PG  - 1401-1408
LID - 10.1038/s41401-020-00562-8 [doi]
AB  - We previously reported that pseudoginsenoside-F11 (PF11), an ocotillol-type 
      saponin, significantly ameliorated Alzheimer's disease (AD)-associated cognitive 
      defects in APP/PS1 and SAMP8 mice by inhibiting Abeta aggregation and tau 
      hyperphosphorylation, suggesting a potential therapeutic effect of PF11 in the 
      treatment of AD. In the present study we further evaluated the therapeutic 
      effects of PF11 on relieving cognitive impairment in a rat model of sporadic AD 
      (SAD). SAD was induced in rats by bilateral icv infusion of streptozotocin (STZ, 
      3 mg/kg). The rats were treated with PF11 (2, 4, 8 mg.kg(-1).d(-1), ig) or a 
      positive control drug donepezil (5 mg.kg(-1).d(-1), ig) for 4 weeks. Their 
      cognitive function was assessed in the nest building, Y-maze, and Morris water 
      maze tests. We showed that STZ icv infusion significantly affected the cognitive 
      function, tau phosphorylation, and insulin signaling pathway in the hippocampus. 
      Furthermore, STZ icv infusion resulted in significant upregulation of the calpain 
      I/cyclin-dependent protein kinase 5 (CDK5) signaling pathway in the hippocampus. 
      Oral administration of PF11 dose-dependently ameliorated STZ-induced learning and 
      memory defects. In addition, PF11 treatment markedly reduced the neuronal loss, 
      protected the synapse structure, and modulated STZ-induced expression of tau 
      phosphorylation by regulating the insulin signaling pathway and calpain I/CDK5 
      signaling pathway in the hippocampus. Donepezil treatment exerted similar 
      beneficial effects in STZ-infused rats as the high dose of PF11 did. This study 
      highlights the excellent therapeutic potential of PF11 in managing AD.
CI  - (c) 2020. CPS and SIMM.
FAU - Zhu, Lei
AU  - Zhu L
AD  - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, 
      China.
FAU - Hou, Xiao-Jie
AU  - Hou XJ
AD  - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, 
      China.
FAU - Che, Xiao-Hang
AU  - Che XH
AD  - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, 
      China.
FAU - Zhou, Ting-Shuo
AU  - Zhou TS
AD  - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, 
      China.
FAU - Liu, Xiao-Qi
AU  - Liu XQ
AD  - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, 
      China.
FAU - Wu, Chun-Fu
AU  - Wu CF
AD  - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, 
      China. wucf@syphu.edu.cn.
FAU - Yang, Jing-Yu
AU  - Yang JY
AD  - Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, 110016, 
      China. yangjingyu2006@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20201204
PL  - United States
TA  - Acta Pharmacol Sin
JT  - Acta pharmacologica Sinica
JID - 100956087
RN  - 0 (Ginsenosides)
RN  - 0 (Insulin Receptor Substrate Proteins)
RN  - 0 (Irs1 protein, rat)
RN  - 0 (pseudoginsenoside F11)
RN  - 0 (tau Proteins)
RN  - 5W494URQ81 (Streptozocin)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Calpain)
SB  - IM
MH  - Alzheimer Disease/chemically induced/*drug therapy
MH  - Animals
MH  - Calpain/metabolism
MH  - Chromosome Pairing
MH  - Cognitive Dysfunction/*drug therapy
MH  - Disease Models, Animal
MH  - Ginsenosides/*pharmacology
MH  - Glycogen Synthase Kinase 3 beta/metabolism
MH  - Hippocampus/metabolism/pathology/ultrastructure
MH  - Insulin Receptor Substrate Proteins/metabolism
MH  - Male
MH  - Maze Learning/drug effects
MH  - Morris Water Maze Test/drug effects
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Streptozocin
MH  - tau Proteins/*metabolism
PMC - PMC8379201
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Tau hyperphosphorylation
OT  - calpain I/CDK5 signaling pathway
OT  - donepezil
OT  - insulin signaling pathway
OT  - pseudoginsenoside-F11
COIS- The authors declare no competing interests.
EDAT- 2020/12/06 06:00
MHDA- 2022/01/29 06:00
PMCR- 2022/09/01
CRDT- 2020/12/05 05:30
PHST- 2020/05/05 00:00 [received]
PHST- 2020/10/20 00:00 [accepted]
PHST- 2020/12/06 06:00 [pubmed]
PHST- 2022/01/29 06:00 [medline]
PHST- 2020/12/05 05:30 [entrez]
PHST- 2022/09/01 00:00 [pmc-release]
AID - 10.1038/s41401-020-00562-8 [pii]
AID - 562 [pii]
AID - 10.1038/s41401-020-00562-8 [doi]
PST - ppublish
SO  - Acta Pharmacol Sin. 2021 Sep;42(9):1401-1408. doi: 10.1038/s41401-020-00562-8. 
      Epub 2020 Dec 4.