Javier Marín-Prida, José Luiz Liberato, Alexey Llópiz-Arzuaga, Karina Stringhetta-Padovani, Nancy Pavón-Fuentes, Andréia Machado Leopoldino, Osmany Guirola Cruz, Ignacio Hernández González, Mariela León Pérez, Antoni Camins, Wagner Ferreira dos Santos, Sergio Akira Uyemura, Gilberto L. Pardo-Andreu and Giselle Pentón-Rol* Pages 1187 - 1197 ( 11 )
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.
C-Phycocyanin, ischemic stroke, NADPH oxidase, neuroprotection, neuroinflammation, brain ischemia.