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Icariside II, a phosphodiesterase 5 inhibitor, attenuates cerebral ischaemia/reperfusion injury by inhibiting glycogen synthase kinase-3?-mediated activation of autophagy.

ABSTRACT: BACKGROUND AND PURPOSE:Cerebral ischaemia/reperfusion causes exacerbated neuronal damage involving excessive autophagy and neuronal loss. The present study was designed to investigate the effect of icariside II, one of main active ingredients of Herba Epimedii on this loss and whether this is related to its PDE 5 inhibitory action. EXPERIMENTAL APPROACH:Focal cerebral ischaemia was induced in the rat by transient middle cerebral artery occlusion over 2 hr, followed by reperfusion with icariside II, 3-methylamphetamine or rapamycin. The effect of icariside II was determined measuring behaviour changes and the size of the infarction. The expressions of PDE 5, autophagy-related proteins and the level of phosphorylation of glycogen synthase kinase-3? (GSK-3?) were determined. Cultured primary cortical neurons were subjected to oxygen and glucose deprivation followed by reoxygenation in the presence and absence of icariside II. A surface plasmon resonance assay and molecular docking were used to explore the interactions of icariside II with PDE 5 or GSK-3?. KEY RESULTS:Icariside II not only protected against induced ischaemic reperfusion injury in rats but also attenuated such injury in primary cortical neurons. The neuroprotective effects of icariside II on such injury were attributed to interfering with the PKG/GSK-3?/autophagy axis by directly bounding to PDE 5 and GSK-3?. CONCLUSIONS AND IMPLICATIONS:These findings indicate that icariside II attenuates cerebral I/R-induced injury via interfering with PKG/GSK-3?/autophagy axis. This study raises the possibility that icariside II and other PDE 5 inhibitors maybe effective in the treatment ischaemia stroke.

PROVIDER: S-EPMC7056470 | BioStudies |

REPOSITORIES: biostudies

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