Ginkgo biloba leaf extract (EGb-۷۶۱) elicits neuroprotection against cerebral ischemia/reperfusion injury by enhancement of autophagy flux in neurons in the penumbra

Objective(s): Ginkgo biloba leaf extract (EGb-۷۶۱) injection has been widely used as adjuvant therapy for cerebral stroke in China. However, its underlying pharmacological mechanism is not completely understood. The present study aimed to investigate whether the therapeutic effects of EGb-۷۶۱ are exerted by modulating autophagy flux. Materials and Methods: Ischemic cerebral stroke was prepared in male Sprague-Dawley rats by middle cerebral artery occlusion (MCAO) followed by reperfusion. The MCAO/reperfusion rats were then treated with EGb-۷۶۱ injection once daily for ۷ days. Thereafter, the brain tissues in the ischemic penumbra were obtained to detect the key proteins in the autophagic/lysosomal pathway with Beclin۱, LC۳, (SQSTM۱)/p۶۲, ubiquitin, LAMP-۱, cathepsin B, and cathepsin D antibodies by western blot and immunofluorescence. Meanwhile, the infarct volume, neurological deficits, and neuronal apoptosis were assessed to evaluate the therapeutic outcomes.Results: The results illustrated that EGb-۷۶۱ treatment was not only able to promote the autophagic activities of Beclin۱ and LC۳-II in neurons, but also could enhance the autophagic clearance, as indicated by reinforced lysosomal activities of LAMP-۱, cathepsin B, and cathepsin D, as well as alleviating autophagic accumulation of ubiquitin and insoluble p۶۲ in the MCAO+EGb-۷۶۱ group, compared with those in the MCAO+saline group. Meanwhile, cerebral ischemia-induced neurological deficits, infarct volume, and neuronal apoptosis were significantly attenuated by ۷ days of EGb-۷۶۱ therapy. Conclusion: Our data suggest that EGb-۷۶۱ injection can elicit a neuroprotective efficacy against MCAO/reperfusion injury, and this neuroprotection may be exerted by enhancement of autophagy flux in neurons in the ischemic penumbra.

کلیدواژه ها:

Autophagy ، Enhancement ، Ginkgo biloba ، Ischemic stroke ، Neuroprotection