Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis

Xiaoqiang Li,1 Deli Zhang,1 Yinliang Bai,1 Jiyuan Xiao,1 Haisheng Jiao,1 Rongxia He21Department of Pharmacy, Lanzhou University Second Hospital, Lanzhou 730030, People’s Republic of China; 2Department of Gynecology, Lanzhou University Second Hospital, Lanzhou 730030, People’s Rep...

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Autores principales:	Li X, Zhang D, Bai Y, Xiao J, Jiao H, He R
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Ginaton ischemic stroke middle cerebral artery occlusion autophagy apoptosis mitochondrial function Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/fb519c6fae67484399c611f324dbaf88
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spelling	oai:doaj.org-article:fb519c6fae67484399c611f324dbaf882021-12-02T05:27:47ZGinaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis1178-2021https://doaj.org/article/fb519c6fae67484399c611f324dbaf882019-07-01T00:00:00Zhttps://www.dovepress.com/ginaton-improves-neurological-function-in-ischemic-stroke-rats-via-ind-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Xiaoqiang Li,1 Deli Zhang,1 Yinliang Bai,1 Jiyuan Xiao,1 Haisheng Jiao,1 Rongxia He21Department of Pharmacy, Lanzhou University Second Hospital, Lanzhou 730030, People’s Republic of China; 2Department of Gynecology, Lanzhou University Second Hospital, Lanzhou 730030, People’s Republic of ChinaPurpose: The present study was carried out to confirm the protective effect of extract of Ginkgo biloba (Ginaton) against ischemic neuronal damage post-treatment at 24 h after reperfusion in rats with middle cerebral artery occlusion (MCAO) and further reveal its possible mechanisms.Methods: Adult male Sprague-Dawley rats were modeled by MCAO for 2 h. The rats were divided into three groups: sham, model, and Ginaton (50 mg/kg). All animals received treatment once a day for 14 days from 24 h after reperfusion. Modified neurological severity score test was performed in 1, 7 and 14 days after MCAO, and beam walking test was performed only 14 days after MCAO. Hematoxylin-eosin straining was implemented to measure infarct volume and immunohistochemical analysis was performed to calculate the number of neurons in ischemic cortex penumbra. Western blot was used to evaluate the expression of autophagy (Beclin1, LC3, AMPK, mTOR, ULK), mitochondrial dynamic protein (Parkin, DRP1, OPA1) and apoptosis (Bcl-2, Bax).Results: Post-treatment with Ginaton for 14 days decreased neurological deficit score, promoted the recovery of motor function, and noticeably reduced infarct size. Besides, Ginaton also alleviated the loss of NeuN-positive cells in ischemic cortex penumbra. In ischemic cortex, Ginaton increased the expression of Beclin1 and LC3-Ⅱ, elevated the AMPK, mTOR and ULK1, and induced autophagy. Moreover, Ginaton treatment upregulated Parkin, DRP1, and OPA1, and elevated the ratio of Bcl-2/Bax in 14 days after MCAO reperfusion injury.Conclusion: Ginaton exhibited obvious neuroprotective effects in MCAO rats with initial administered 24 h after MCAO. The mechanism of Ginaton included induction of autophagy via activation of the AMPK pathway, maintenance of mitochondrial homeostasis and inhibition of apoptosis.Keywords: Ginaton, ischemic stroke, middle cerebral artery occlusion, autophagy, apoptosis, mitochondrial functionLi XZhang DBai YXiao JJiao HHe RDove Medical PressarticleGinatonischemic strokemiddle cerebral artery occlusionautophagyapoptosismitochondrial functionNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 15, Pp 1813-1822 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ginaton ischemic stroke middle cerebral artery occlusion autophagy apoptosis mitochondrial function Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Ginaton ischemic stroke middle cerebral artery occlusion autophagy apoptosis mitochondrial function Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Li X Zhang D Bai Y Xiao J Jiao H He R Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis
description	Xiaoqiang Li,1 Deli Zhang,1 Yinliang Bai,1 Jiyuan Xiao,1 Haisheng Jiao,1 Rongxia He21Department of Pharmacy, Lanzhou University Second Hospital, Lanzhou 730030, People’s Republic of China; 2Department of Gynecology, Lanzhou University Second Hospital, Lanzhou 730030, People’s Republic of ChinaPurpose: The present study was carried out to confirm the protective effect of extract of Ginkgo biloba (Ginaton) against ischemic neuronal damage post-treatment at 24 h after reperfusion in rats with middle cerebral artery occlusion (MCAO) and further reveal its possible mechanisms.Methods: Adult male Sprague-Dawley rats were modeled by MCAO for 2 h. The rats were divided into three groups: sham, model, and Ginaton (50 mg/kg). All animals received treatment once a day for 14 days from 24 h after reperfusion. Modified neurological severity score test was performed in 1, 7 and 14 days after MCAO, and beam walking test was performed only 14 days after MCAO. Hematoxylin-eosin straining was implemented to measure infarct volume and immunohistochemical analysis was performed to calculate the number of neurons in ischemic cortex penumbra. Western blot was used to evaluate the expression of autophagy (Beclin1, LC3, AMPK, mTOR, ULK), mitochondrial dynamic protein (Parkin, DRP1, OPA1) and apoptosis (Bcl-2, Bax).Results: Post-treatment with Ginaton for 14 days decreased neurological deficit score, promoted the recovery of motor function, and noticeably reduced infarct size. Besides, Ginaton also alleviated the loss of NeuN-positive cells in ischemic cortex penumbra. In ischemic cortex, Ginaton increased the expression of Beclin1 and LC3-Ⅱ, elevated the AMPK, mTOR and ULK1, and induced autophagy. Moreover, Ginaton treatment upregulated Parkin, DRP1, and OPA1, and elevated the ratio of Bcl-2/Bax in 14 days after MCAO reperfusion injury.Conclusion: Ginaton exhibited obvious neuroprotective effects in MCAO rats with initial administered 24 h after MCAO. The mechanism of Ginaton included induction of autophagy via activation of the AMPK pathway, maintenance of mitochondrial homeostasis and inhibition of apoptosis.Keywords: Ginaton, ischemic stroke, middle cerebral artery occlusion, autophagy, apoptosis, mitochondrial function
format	article
author	Li X Zhang D Bai Y Xiao J Jiao H He R
author_facet	Li X Zhang D Bai Y Xiao J Jiao H He R
author_sort	Li X
title	Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis
title_short	Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis
title_full	Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis
title_fullStr	Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis
title_full_unstemmed	Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis
title_sort	ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/fb519c6fae67484399c611f324dbaf88
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Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis

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