Protective Effects of Oleuropein Against Cerebral Ischemia/Reperfusion by Inhibiting Neuronal Apoptosis
Weijing Zhang, Xiaogang Liu, Qiuyue Li
(Department of Nursing, Tangshan Gongren Hospital, Tangshan, Hebei, China (mainland))
Med Sci Monit 2018; 24:6587-6598
In this study, we investigated the potential neuroprotective effect of oleuropein (OLE) on apoptotic changes via modulating Akt/glycogen synthase kinase 3 beta (Akt/GSK-3b) signaling in a rat model of cerebral ischemia/reperfusion injury (IRI).
MATERIAL AND METHODS: Sprague-Dawley male rats (12 weeks, n=200) were randomly assigned to 5 groups: sham group, vehicle (IRI+ vehicle) group, OLE (IRI+OLE) group, OLE+LY294002 (IRI+OLE+LY294002) group, and LY294002(IRI+LY294002) group. The rats were subjected to cerebral ischemia/reperfusion injury (IRI) model and treated once daily for 5 days with vehicle and OLE (100 mg/kg via intraperitoneal injection) after IRI injury. LY294002 (0.3 mg/kg) was intraperitoneally injected once at 30 min after IRI injury. Brain edema, neurological deficit, rotarod latencies, and Morris water maze (MWM) performance were evaluated after IRI. The number of dead cells were assayed by TUNEL staining. Western blot was used to detect the expression of Bcl-2, Bax, cleaved caspase-3 (CC3), neurotrophic factors, and the phosphorylation levels of Akt and GSK-3β.
RESULTS: Compared with the vehicle group, brain water content, neurological deficits, rotarod latencies, and escape latency following IRI were reduced in the OLE group. Cell apoptosis and reduced neurotrophic factor caused by IRI was also attenuated by OLE. Furthermore, increased p-Akt and decreased p-GSK-3β were caused by OLE, which were associated with decrease of Bax/Bcl-2 ratio and the suppression of Caspase-3 activity after IRI. Importantly, all the beneficial effects of OLE in the vehicle group were abrogated by PI3K inhibitor LY294002.
CONCLUSIONS: Cerebral ischemia was protected by OLE via suppressing apoptosis through the Akt/GSK-3β pathway and upregulating neurotrophic factor after IRI.
Keywords: Apoptosis, Brain Ischemia, Olea, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt