Novel Insights into the Molecular Mechanisms Involved in the Neuroprotective Effects of C-Phycocyanin against Brain Ischemia in Rats.
Curr Pharm Des
; 28(14): 1187-1197, 2022.
Article
em En
| MEDLINE
| ID: mdl-35524676
ABSTRACT
BACKGROUND:
Ischemic stroke produces a large health impact worldwide, with scarce therapeutic options.OBJECTIVE:
This study aimed to reveal the role of NADPH oxidase and neuroinflammatory genes in the cerebral anti-ischemic effects of C-Phycocyanin (C-PC), the chief biliprotein of Spirulina platensis.METHODS:
Rats with either focal cerebral ischemia/reperfusion (I/R) or acute brain hypoperfusion, received C-PC at different doses, or a vehicle, for up to 6 h post-stroke. Neurological, behavioral and histochemical parameters were assessed in I/R rats at 24 h. Cerebral gene expression and hippocampal neuron viability were evaluated in hypoperfused rats at acute (24 h) or chronic phases (30 days), respectively. A molecular docking analysis of NOX2 and C-PC-derived Phycocyanobilin (PCB) was also performed.RESULTS:
C-PC, obtained with a purity of 4.342, significantly reduced the infarct volume and neurological deficit in a dose-dependent manner, and improved the exploratory activity of I/R rats. This biliprotein inhibited NOX2 expression, a crucial NADPH oxidase isoform in the brain, and the superoxide increase produced by the ischemic event. Moreover, C-PC-derived PCB showed a high binding affinity in silico with NOX2. C-PC downregulated the expression of pro-inflammatory genes (IFN-γ, IL-6, IL-17A, CD74, CCL12) and upregulated immune suppressive genes (Foxp3, IL-4, TGF-ß) in hypoperfused brain areas. This compound also decreased chronic neuronal death in the hippocampus of hypoperfused rats.CONCLUSION:
These results suggest that the inhibition of cerebral NADPH oxidase and the improvement of neuroinflammation are key mechanisms mediating the neuroprotective actions of C-PC against brain ischemia.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
/
Isquemia Encefálica
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Fármacos Neuroprotetores
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article