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

Autor:	Marín-Prida J; Center for Research and Biological Evaluations, Institute of Pharmacy and Food, University of Havana, Havana, Cuba., Liberato JL; Faculty of Philosophy, Sciences and Literature of Ribeirão Preto, University of São Paulo, Brazil., Llópiz-Arzuaga A; Center for Genetic Engineering and Biotechnology, Havana, Cuba.; Departamento de Ingeniería Celular y Biocatálisis, Instituto de Biotecnología, Universidad Nacional Autónoma de México, Morelos, México., Stringhetta-Padovani K; Department of Clinical Analyses, Toxicology and Food Sciences, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil., Pavón-Fuentes N; International Center for Neurological Restoration, Havana, Cuba., Leopoldino AM; Department of Clinical Analyses, Toxicology and Food Sciences, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil., Cruz OG; Center for Genetic Engineering and Biotechnology, Havana, Cuba., González IH; Isotopes Center, Ave. Monumental Km 3.5, San José de Las Lajas, Mayabeque, Cuba., Pérez ML; Isotopes Center, Ave. Monumental Km 3.5, San José de Las Lajas, Mayabeque, Cuba., Camins A; Department of Pharmacology, Toxicology and Therapeutic Chemistry, Faculty of Pharmacy and Food Science, University of Barcelona, Barcelona, Spain.; Institute of Neuroscience, University of Barcelona, Barcelona, Spain.; Biomedical Research Networking Centre in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Ferreira Dos Santos W; Faculty of Philosophy, Sciences and Literature of Ribeirão Preto, University of São Paulo, Brazil., Uyemura SA; Department of Clinical Analyses, Toxicology and Food Sciences, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Brazil., Pardo-Andreu GL; Center for Research and Biological Evaluations, Institute of Pharmacy and Food, University of Havana, Havana, Cuba., Pentón-Rol G; Center for Genetic Engineering and Biotechnology, Havana, Cuba.; Latin American School of Medicine, Playa, Havana, Cuba.
Jazyk:	angličtina
Zdroj:	Current pharmaceutical design [Curr Pharm Des] 2022; Vol. 28 (14), pp. 1187-1197.
DOI:	10.2174/1381612828666220506145542
Abstrakt:	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-β) 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. (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Databáze:	MEDLINE
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