AngIV-Analog Dihexa Rescues Cognitive Impairment and Recovers Memory in the APP/PS1 Mouse via the PI3K/AKT Signaling Pathway.

Sun X, Deng Y, Fu X, Wang S, Duan R, Zhang Y

Brain sciences11 Nov 2021Cited by 12 (Europe PMC)

PMID34827486PMCIDPMC8615599DOI10.3390/brainsci11111487PepBankPUB-34827486

Summary

The renin-angiotensin system (RAS) is a paracrine RAS within the central nervous system (CNS) and is closely related to Alzheimer's disease (AD). The endogenous hexapeptide angiotensin IV (Ang IV), an important component of the brain RAS, was found to rescue cognitive impairment and recover memory in previous studies. In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice. We found that the amount of AngIV in mouse tissue increased after the administration of Dihexa compared to that in the WT group. Meanwhile, Dihexa restored spatial learning and cognitive functions in the Morris water maze test. Dihexa increased the neuronal cells and the expression of SYP protein in APP/PS1 mice in Nissl staining. Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α and increased the levels of the anti-inflammatory cytokine IL-10. Dihexa activated the PI3K/AKT signaling pathway, while PI3K inhibitor wortmannin significantly reversed the anti-inflammatory and anti-apoptotic effects of APP/PS1 mice. These findings highlight the brain AngIV/PI3K/AKT axis as a potential target for the treatment of AD.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study13

11 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Mechanism
In APP/PS1 mice, tissue AngIV increased after Dihexa administration compared with the WT group.
In plain wordsIn mice, tissue AngIV increased after Dihexa administration compared with the WT group.
Peptide
Dihexa
Outcome
IncreaseTissue AngIV amount
Study
Mousen: not reported in source
APP/PS1 mice
Comparator
WT group
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
We found that the amount of AngIV in mouse tissue increased after the administration of Dihexa compared to that in the WT group.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
Show in the study text Report a problemFND-3482748601
02AnimalAnimal study (in vivo)Efficacy outcome
In APP/PS1 mice, Dihexa restored spatial learning in the Morris water maze test.
In plain wordsIn mice, Dihexa restored spatial learning in a water maze test.
Peptide
Dihexa
Outcome
IncreaseSpatial learning
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Meanwhile, Dihexa restored spatial learning and cognitive functions in the Morris water maze test.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
Show in the study text Report a problemFND-3482748602
03AnimalAnimal study (in vivo)Efficacy outcome
In APP/PS1 mice, Dihexa restored cognitive function in the Morris water maze test.
In plain wordsIn mice, Dihexa restored cognitive function in a water maze test.
Peptide
Dihexa
Outcome
IncreaseCognitive function
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Cognition and memory · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Meanwhile, Dihexa restored spatial learning and cognitive functions in the Morris water maze test.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
Show in the study text Report a problemFND-3482748603
04AnimalAnimal study (in vivo)Mechanism
In APP/PS1 mice, Dihexa increased neuronal cells assessed by Nissl staining.
In plain wordsIn mice, Dihexa increased nerve cells assessed by tissue staining.
Peptide
Dihexa
Outcome
IncreaseNeuronal cells
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Dihexa increased the neuronal cells and the expression of SYP protein in APP/PS1 mice in Nissl staining.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
Show in the study text Report a problemFND-3482748604
05AnimalAnimal study (in vivo)Mechanism
In APP/PS1 mice, Dihexa increased SYP protein expression.
In plain wordsIn mice, Dihexa increased SYP protein expression.
Peptide
Dihexa
Outcome
IncreaseSYP protein expression
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Dihexa increased the neuronal cells and the expression of SYP protein in APP/PS1 mice in Nissl staining.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
Show in the study text Report a problemFND-3482748605
06AnimalAnimal study (in vivo)Mechanism
In APP/PS1 mice, Dihexa decreased astrocyte activation.
In plain wordsIn mice, Dihexa decreased astrocyte activation.
Peptide
Dihexa
Outcome
DecreaseAstrocyte activation
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α and increased the levels of the anti-inflammatory cytokine IL-10.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
Show in the study text Report a problemFND-3482748606
07AnimalAnimal study (in vivo)Mechanism
In APP/PS1 mice, Dihexa decreased microglial activation.
In plain wordsIn mice, Dihexa decreased microglial activation.
Peptide
Dihexa
Outcome
DecreaseMicroglial activation
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α and increased the levels of the anti-inflammatory cytokine IL-10.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
Show in the study text Report a problemFND-3482748607
08AnimalAnimal study (in vivo)Mechanism
In APP/PS1 mice, Dihexa markedly reduced IL-1β levels.
In plain wordsIn mice, Dihexa reduced IL-1β levels.
Peptide
Dihexa
Outcome
DecreaseIL-1β levels
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α and increased the levels of the anti-inflammatory cytokine IL-10.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
Show in the study text Report a problemFND-3482748608
09AnimalAnimal study (in vivo)Mechanism
In APP/PS1 mice, Dihexa markedly reduced TNF-α levels.
In plain wordsIn mice, Dihexa reduced TNF-α levels.
Peptide
Dihexa
Outcome
DecreaseTNF-α levels
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α and increased the levels of the anti-inflammatory cytokine IL-10.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
Show in the study text Report a problemFND-3482748609
10AnimalAnimal study (in vivo)Mechanism
In APP/PS1 mice, Dihexa increased IL-10 levels.
In plain wordsIn mice, Dihexa increased IL-10 levels.
Peptide
Dihexa
Outcome
IncreaseIL-10 levels
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Inflammation markers · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Furthermore, Dihexa decreased the activation of astrocytes and microglia, markedly reduced levels of the pro-inflammatory cytokines IL-1β and TNF-α and increased the levels of the anti-inflammatory cytokine IL-10.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
Show in the study text Report a problemFND-3482748610
11AnimalAnimal study (in vivo)Mechanism
In APP/PS1 mice, Dihexa activated PI3K/AKT signaling.
In plain wordsIn mice, Dihexa activated PI3K/AKT signaling.
Peptide
Dihexa
Outcome
IncreasePI3K/AKT pathway activation
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Receptor activity and mechanism · Nervous system and cognition
Studied dose
Dose not stated
Source sentences
Summary
Dihexa activated the PI3K/AKT signaling pathway, while PI3K inhibitor wortmannin significantly reversed the anti-inflammatory and anti-apoptotic effects of APP/PS1 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
Show in the study text Report a problemFND-3482748611

Studies that did not test the peptide alone2

In this study, Dihexa was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Dihexa.

12AnimalNot a test of Dihexa aloneAnimal study (in vivo)Mechanism
In APP/PS1 mice, wortmannin significantly reversed the anti-inflammatory effects associated with Dihexa.
In plain wordsIn mice, wortmannin reversed the anti-inflammatory effects associated with Dihexa.
Peptide
Dihexa
Outcome
DecreaseAnti-inflammatory effect reversal
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Inflammation markers · Nervous system and cognition
Source sentences
Summary
Dihexa activated the PI3K/AKT signaling pathway, while PI3K inhibitor wortmannin significantly reversed the anti-inflammatory and anti-apoptotic effects of APP/PS1 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
In this study, Dihexa was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dihexa.
Show in the study text Report a problemFND-3482748612
13AnimalNot a test of Dihexa aloneAnimal study (in vivo)Mechanism
In APP/PS1 mice, wortmannin significantly reversed the anti-apoptotic effects associated with Dihexa.
In plain wordsIn mice, wortmannin reversed the effects against cell death associated with Dihexa.
Peptide
Dihexa
Outcome
DecreaseAnti-apoptotic effect reversal
Study
Mousen: not reported in source
APP/PS1 mice
Outcome group
Neuroprotection · Nervous system and cognition
Source sentences
Summary
Dihexa activated the PI3K/AKT signaling pathway, while PI3K inhibitor wortmannin significantly reversed the anti-inflammatory and anti-apoptotic effects of APP/PS1 mice.
1 context sentence(design, population, supporting numbers)
Summary · context
In our study, we used different doses of Dihexa, which can be orally administered and cross the BBB in APP/PS1 mice.
In this study, Dihexa was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Dihexa.
Show in the study text Report a problemFND-3482748613

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
14 Oct 2026, 05:02 UTC
Study results updated
Version 1
14 Oct 2026, 01:45 UTC
First added · source update from Europe PMC

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