Novel Insights into the Molecular Mechanisms Involved in the Neuroprotective Effects of C-Phycocyanin against Brain Ischemia in Rats

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Marin-Prida, Javier ; Liberato, Jose Luiz ; Llopiz-Arzuaga, Alexey ; Stringhetta-Padovani, Karina ; Pavon-Fuentes, Nancy ; Machado Leopoldino, Andreia ; Guirola Cruz, Osmany ; Hernandez Gonzalez, Ignacio ; Leon Perez, Mariela ; Camins, Antoni ; dos Santos, Wagner Ferreira ; Akira Uyemura, Sergio ; Pardo-Andreu, Gilberto L. ; Penton-Rol, Giselle

• Tipo de documento: Artigo Científico
• Fonte: CURRENT PHARMACEUTICAL DESIGN; v. 28, n. 14, p. 11-pg., 2022-01-01.

Resumo

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-gamma, IL-6, IL-17A, CD74, CCL12) and upregulated immune suppressive genes (Foxp3, IL-4, TGF-beta) 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. (AU)

• Processo FAPESP: 13/10898-4 - Estudo dos mecanismos moleculares associados à proteína SET com impacto na tumorigênese e progressão do câncer oral
• Beneficiário: Carlos Curti
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/00374-8 - Análise da proteína hnRNPK nas linhagens celulares NB4 e NB4-R2 de leucemia promielocítica aguda com ênfase na patogênese e na diferenciação celular pelo ácido all-trans retinóico
• Beneficiário: Karina Stringhetta Padovani
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto