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Ginkgo Biloba Extract Promotes Neuronal Autophagy and Improves Neuroprotection in Penumbra of Cerebral Ischemia


GUO Tao, WU Zhiyuan, ZHAO Xiaoming, CHEN Xuemei, LIU Yuyuan, HUANG Zhiwen, HE Hongyun*, DENG Yihao*

(Department of Anatomy, Faculty of Medicine, Kunming University of Science and Technology, Stroke Pathological Mechanism Research Laboratory, Kunming 650500, China)
Abstract:

EGb-761 (ginkgo biloba extract-761) injection has been widely used as an adjuvantive therapy for cerebral stroke in China, but its underlying cellular and pharmacological mechanisms have not been fully understood. This study aims to investigate whether EGb-761 has a therapeutic effect by regulating the autophagy of neurons in the penumbra of ischemic stroke. Using the MCAO (middle cerebral artery occlusion) reperfusion model of male SD rats, the MCAO rats were randomly divided into 5 groups, namely Sham group, MCAO+saline group, MCAO+EGb group, MCAO+EGb+3-MA group and MCAO+3-MA group. Cerebral ischemic rats were injected intraperitoneally with EGb-761 for 7 days, and were injected with autophagy inhibitor 3-MA into the lateral ventricle. The brain tissue of the ischemic penumbra was used to detect the expression of autophagy by WB, qRT-PCR (quantitative real-time PCR) and immunofluorescence. In addition, the evaluation of therapeutic efficacy was based on cerebral infarction volume, neurological deficit, and TUNEL detection of neuronal apoptosis levels. The results showed that compared with MCAO+saline, the EGb-761 drug in the MCAO+EGb group significantly increased the expression of neuronal autophagy. At the same time, EGb-761 treatment significantly reduced the neurological deficit, cerebral infarction area and neuronal apoptosis. In addition, 3-MA in the MCAO+EGb+3-MA group counteracted the effect of EGb to enhance neuronal autophagy, and only the use of 3-MA continued to aggravate the nerve damage, compared with the MCAO+EGb group. Therefore, EGB-761 exerts a neuroprotective effect by specifically promoting neuronal autophagy in the penumbra of cerebral ischemia.