Activation of the Melanocortin-1 Receptor by NDP-MSH Attenuates Oxidative Stress and Neuronal Apoptosis through PI3K/Akt/Nrf2 Pathway after Intracerebral Hemorrhage in Mice.

Fu S, Luo X, Wu X, Zhang T, Gu L, Wang Y, Gao M, Cheng Y, Xie Z

Oxidative medicine and cellular longevity12 Nov 2020Cited by 37 (Europe PMC)

PMID33274009PMCIDPMC7676969DOI10.1155/2020/8864100PepBankPUB-33274009

Summary

Oxidative stress and neuronal apoptosis play crucial roles in secondary brain injury (SBI) after intracerebral hemorrhage (ICH). Recently, Nle4-D-Phe7-α-melanocyte-stimulating hormone (NDP-MSH), a synthetic agonist of the melanocortin-1 receptor (Mc1r), has been proved to inhibit neuroinflammatory in several diseases. This study is aimed at exploring if NDP-MSH could reduce oxidative stress and neuronal apoptosis following ICH, as well as the potential mechanism. A mouse ICH model was induced by autologous blood injection. NDP-MSH was intraperitoneally injected at 1 h after ICH. Mc1r siRNA and PI3K inhibitor LY294002 were administrated to inhibit the expression of Mc1r and phosphorylation of PI3K, respectively. Neurological test, brain water content, enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), immunofluorescence, and Western blot analysis were utilized in this study. The results exhibited that Mc1r was mainly expressed in neurons, and its level in the ipsilateral hemisphere was significantly elevated after ICH. NDP-MSH treatment significantly attenuated the neurological deficits and brain water content 24 hours after ICH, which was accompanied by the inhibition of oxidative stress and neuronal apoptosis. The administration of NDP-MSH after ICH significantly promoted the expression of Mc1r, p-PI3K, p-Akt, and p-Nrf2, followed by an increase of Bcl-2 and reduction of cleaved caspase-3. Conversely, downregulating the expression of Mc1r and phosphorylation of PI3K aggravated the neurological deficits and brain edema at 24 hours after ICH, meanwhile, the effect of NDP-MSH on the expression of Mc1r, p-PI3K, p-Akt, p-Nrf2, Bcl-2, and cleaved caspase 3 was also abolished. In conclusion, our data suggest that the activation of Mc1r by NDP-MSH ameliorates oxidative stress and neuronal apoptosis through the PI3K/Akt/Nrf2 signaling pathway after ICH in mice.

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

Results from this study11

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

01AnimalAnimal study (in vivo)Efficacy outcome
In mice with intracerebral hemorrhage, NDP-MSH treatment significantly attenuated neurological deficits at 24 hours.
In plain wordsIn mice with bleeding in the brain, NDP-MSH reduced nerve function problems 24 hours later.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseNeurological deficits 24 hours after ICH
Study
Mousen: not reported in source
Autologous blood injection model of intracerebral hemorrhage
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · intraperitonealAs given in this study (Mouse).
Source sentences
Summary
NDP-MSH treatment significantly attenuated the neurological deficits and brain water content 24 hours after ICH
1 context sentence(design, population, supporting numbers)
Summary · context
A mouse ICH model was induced by autologous blood injection.
Show in the study text Report a problemFND-3327400901
02AnimalAnimal study (in vivo)Efficacy outcome
In mice with intracerebral hemorrhage, NDP-MSH treatment significantly attenuated brain water content at 24 hours.
In plain wordsIn mice with bleeding in the brain, NDP-MSH reduced brain swelling 24 hours later.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseBrain water content 24 hours after ICH
Study
Mousen: not reported in source
Autologous blood injection model of intracerebral hemorrhage
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · intraperitonealAs given in this study (Mouse).
Source sentences
Summary
NDP-MSH treatment significantly attenuated the neurological deficits and brain water content 24 hours after ICH
1 context sentence(design, population, supporting numbers)
Summary · context
A mouse ICH model was induced by autologous blood injection.
Show in the study text Report a problemFND-3327400902
03AnimalAnimal study (in vivo)Mechanism
In mice with intracerebral hemorrhage, NDP-MSH treatment was accompanied by inhibition of oxidative stress.
In plain wordsIn mice with bleeding in the brain, NDP-MSH treatment came with lower oxidative stress.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseOxidative stress
Study
Mousen: not reported in source
Autologous blood injection model of intracerebral hemorrhage
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · intraperitonealAs given in this study (Mouse).
Source sentences
Summary
NDP-MSH treatment significantly attenuated the neurological deficits and brain water content 24 hours after ICH, which was accompanied by the inhibition of oxidative stress and neuronal apoptosis.
1 context sentence(design, population, supporting numbers)
Summary · context
A mouse ICH model was induced by autologous blood injection.
Show in the study text Report a problemFND-3327400903
04AnimalAnimal study (in vivo)Mechanism
In mice with intracerebral hemorrhage, NDP-MSH treatment was accompanied by inhibition of neuronal apoptosis.
In plain wordsIn mice with bleeding in the brain, NDP-MSH treatment came with less nerve cell death.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseNeuronal apoptosis
Study
Mousen: not reported in source
Autologous blood injection model of intracerebral hemorrhage
Outcome group
Neuroprotection · Nervous system and cognition
Studied dose
Dose not stated · intraperitonealAs given in this study (Mouse).
Source sentences
Summary
NDP-MSH treatment significantly attenuated the neurological deficits and brain water content 24 hours after ICH, which was accompanied by the inhibition of oxidative stress and neuronal apoptosis.
1 context sentence(design, population, supporting numbers)
Summary · context
A mouse ICH model was induced by autologous blood injection.
Show in the study text Report a problemFND-3327400904
05AnimalAnimal study (in vivo)Mechanism
In mice with intracerebral hemorrhage, NDP-MSH significantly promoted the expression of Mc1r.
In plain wordsIn mice with bleeding in the brain, NDP-MSH raised the amount of the Mc1r receptor.
Peptide
Melanotan I (afamelanotide)
Outcome
IncreaseMc1r expression
Study
Mousen: not reported in source
Autologous blood injection model of intracerebral hemorrhage
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated · intraperitonealAs given in this study (Mouse).
Source sentences
Summary
The administration of NDP-MSH after ICH significantly promoted the expression of Mc1r, p-PI3K, p-Akt, and p-Nrf2, followed by an increase of Bcl-2 and reduction of cleaved caspase-3.
1 context sentence(design, population, supporting numbers)
Summary · context
A mouse ICH model was induced by autologous blood injection.
Show in the study text Report a problemFND-3327400905
06AnimalAnimal study (in vivo)Mechanism
In mice with intracerebral hemorrhage, NDP-MSH significantly promoted the expression of p-PI3K.
In plain wordsIn mice with bleeding in the brain, NDP-MSH raised the level of active PI3K.
Peptide
Melanotan I (afamelanotide)
Outcome
Increasep-PI3K expression
Study
Mousen: not reported in source
Autologous blood injection model of intracerebral hemorrhage
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated · intraperitonealAs given in this study (Mouse).
Source sentences
Summary
The administration of NDP-MSH after ICH significantly promoted the expression of Mc1r, p-PI3K, p-Akt, and p-Nrf2, followed by an increase of Bcl-2 and reduction of cleaved caspase-3.
1 context sentence(design, population, supporting numbers)
Summary · context
A mouse ICH model was induced by autologous blood injection.
Show in the study text Report a problemFND-3327400906
07AnimalAnimal study (in vivo)Mechanism
In mice with intracerebral hemorrhage, NDP-MSH significantly promoted the expression of p-Akt.
In plain wordsIn mice with bleeding in the brain, NDP-MSH raised the level of active Akt.
Peptide
Melanotan I (afamelanotide)
Outcome
Increasep-Akt expression
Study
Mousen: not reported in source
Autologous blood injection model of intracerebral hemorrhage
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated · intraperitonealAs given in this study (Mouse).
Source sentences
Summary
The administration of NDP-MSH after ICH significantly promoted the expression of Mc1r, p-PI3K, p-Akt, and p-Nrf2, followed by an increase of Bcl-2 and reduction of cleaved caspase-3.
1 context sentence(design, population, supporting numbers)
Summary · context
A mouse ICH model was induced by autologous blood injection.
Show in the study text Report a problemFND-3327400907
08AnimalAnimal study (in vivo)Mechanism
In mice with intracerebral hemorrhage, NDP-MSH significantly promoted the expression of p-Nrf2.
In plain wordsIn mice with bleeding in the brain, NDP-MSH raised the level of active Nrf2.
Peptide
Melanotan I (afamelanotide)
Outcome
Increasep-Nrf2 expression
Study
Mousen: not reported in source
Autologous blood injection model of intracerebral hemorrhage
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated · intraperitonealAs given in this study (Mouse).
Source sentences
Summary
The administration of NDP-MSH after ICH significantly promoted the expression of Mc1r, p-PI3K, p-Akt, and p-Nrf2, followed by an increase of Bcl-2 and reduction of cleaved caspase-3.
1 context sentence(design, population, supporting numbers)
Summary · context
A mouse ICH model was induced by autologous blood injection.
Show in the study text Report a problemFND-3327400908
09AnimalAnimal study (in vivo)Mechanism
In mice with intracerebral hemorrhage, NDP-MSH was followed by an increase of Bcl-2.
In plain wordsIn mice with bleeding in the brain, NDP-MSH was followed by a rise in the protective protein Bcl-2.
Peptide
Melanotan I (afamelanotide)
Outcome
IncreaseBcl-2 expression
Study
Mousen: not reported in source
Autologous blood injection model of intracerebral hemorrhage
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated · intraperitonealAs given in this study (Mouse).
Source sentences
Summary
The administration of NDP-MSH after ICH significantly promoted the expression of Mc1r, p-PI3K, p-Akt, and p-Nrf2, followed by an increase of Bcl-2 and reduction of cleaved caspase-3.
1 context sentence(design, population, supporting numbers)
Summary · context
A mouse ICH model was induced by autologous blood injection.
Show in the study text Report a problemFND-3327400909
10AnimalAnimal study (in vivo)Mechanism
In mice with intracerebral hemorrhage, NDP-MSH was followed by a reduction of cleaved caspase-3.
In plain wordsIn mice with bleeding in the brain, NDP-MSH was followed by a drop in cleaved caspase-3, a cell-death marker.
Peptide
Melanotan I (afamelanotide)
Outcome
DecreaseCleaved caspase-3
Study
Mousen: not reported in source
Autologous blood injection model of intracerebral hemorrhage
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated · intraperitonealAs given in this study (Mouse).
Source sentences
Summary
The administration of NDP-MSH after ICH significantly promoted the expression of Mc1r, p-PI3K, p-Akt, and p-Nrf2, followed by an increase of Bcl-2 and reduction of cleaved caspase-3.
1 context sentence(design, population, supporting numbers)
Summary · context
A mouse ICH model was induced by autologous blood injection.
Show in the study text Report a problemFND-3327400910
11AnimalAnimal study (in vivo)Mechanism
In mice with intracerebral hemorrhage, downregulating Mc1r or PI3K phosphorylation abolished the effect of NDP-MSH on Mc1r, p-PI3K, p-Akt, p-Nrf2, Bcl-2 and cleaved caspase 3.
In plain wordsIn mice with bleeding in the brain, blocking Mc1r or PI3K removed the effects of NDP-MSH on these pathway proteins.
Peptide
Melanotan I (afamelanotide)
Outcome
Not applicableNDP-MSH effect on pathway markers after Mc1r siRNA or PI3K inhibitor
Study
Mousen: not reported in source
Autologous blood injection model of intracerebral hemorrhage
Outcome group
Receptor activity and mechanism · Pharmacology
Studied dose
Dose not stated · intraperitonealAs given in this study (Mouse).
Source sentences
Summary
meanwhile, the effect of NDP-MSH on the expression of Mc1r, p-PI3K, p-Akt, p-Nrf2, Bcl-2, and cleaved caspase 3 was also abolished.
1 context sentence(design, population, supporting numbers)
Summary · context
A mouse ICH model was induced by autologous blood injection.
Show in the study text Report a problemFND-3327400911

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
13 Oct 2026, 21:44 UTC
Study results updated
Version 1
13 Oct 2026, 16:31 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

PepBank is a research reference. Talk to a doctor before you use any peptide.