Ginkgo biloba extract and its diterpene ginkgolide constituents ameliorate the metabolic disturbances caused by recombinant tissue plasminogen activator in rat prefrontal cortex

Zhi Chen,1–3,* Shunjie Bai,1–4,* Qingchuan Hu,1–4,* Peng Shen,2,3,5,* Ting Wang,2–4,* Zihong Liang,2,3,5,6,* Wei Wang,1–3 Xunzhong Qi,2,3,5 Peng Xie1,2,4–6 1Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqi...

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Autores principales:	Chen Z, Bai S, Hu Q, Shen P, Wang T, Liang Z, Wang W, Qi X, Xie P
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	Recombinant tissue plasminogen activator (rtPA) diterpene ginkgolides (DG) Ginkgo Biloba Extract (GBE) metabolomics prefrontal cortex excitotoxicity Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/a9c2c0ae405542dc8b22297a71c5b181
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spelling	oai:doaj.org-article:a9c2c0ae405542dc8b22297a71c5b1812021-12-02T08:11:01ZGinkgo biloba extract and its diterpene ginkgolide constituents ameliorate the metabolic disturbances caused by recombinant tissue plasminogen activator in rat prefrontal cortex1178-2021https://doaj.org/article/a9c2c0ae405542dc8b22297a71c5b1812018-07-01T00:00:00Zhttps://www.dovepress.com/ginkgo-biloba-extract-and-its-diterpene-ginkgolide-constituents-amelio-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Zhi Chen,1–3,* Shunjie Bai,1–4,* Qingchuan Hu,1–4,* Peng Shen,2,3,5,* Ting Wang,2–4,* Zihong Liang,2,3,5,6,* Wei Wang,1–3 Xunzhong Qi,2,3,5 Peng Xie1,2,4–6 1Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China; 2Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; 3Chongqing Key Laboratory of Neurobiology, Chongqing, China; 4Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China; 5Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 6Department of Neurology, The Inner Mongolia Autonomous Region People’s Hospital, Hohhot, Inner Mongolia, China *These authors contributed equally to this work Introduction: Although recombinant tissue plasminogen activator (rtPA) is a widely used therapy in patients with acute ischemic stroke, rtPA-induced toxicity or its adverse effects have been reported in our previous studies. However, Ginkgo biloba extract (GBE) may provide neuroprotective effects against rtPA-induced toxicity. Thus, in the present study, we investigated whether a single administration of rtPA caused neurotoxicity in the prefrontal cortex (PFC) of rats and determined whether GBE or its diterpene ginkgolide (DG) constituents were neuroprotective against any rtPA-induced toxicity. Materials and methods: We randomly divided adult Sprague-Dawley rats into four groups that were intravenously administered saline, rtPA, rtPA+DG, or rtPA+GBE. The rats were sacrificed 24 hours later and the whole brain removed. A gas chromatography–mass spectrometry metabolomic approach was used to detect molecular changes in the PFC among the groups. Multivariate statistical and pathway analyses were used to determine the relevant metabolites as well as their functions and pathways. Results: We found 32 metabolites differentially altered in the four groups that were primarily involved in neurotransmitter, amino acid, energy, lipid, and nucleotide metabolism. Our results indicated that a single rtPA administration caused metabolic disturbances in the PFC. Both GBE and DG effectively ameliorated these rtPA-induced disturbances, although DG better controlled the rtPA-induced glutamate and aspartate excitotoxicity and the activation of NMDA receptor. Conclusion: Our results provide important novel mechanistic insights into the adverse effects of rtPA and offer directions for future exploration on the thrombolytic effects of rtPA combined with the administration of DG or GBE for the treatment of acute ischemic stroke in humans. Keywords: recombinant tissue plasminogen activator (rtPA), diterpene ginkgolides (DG), Ginkgo biloba extract (GBE), metabolomics, prefrontal cortex, excitotoxicityChen ZBai SHu QShen PWang TLiang ZWang WQi XXie PDove Medical PressarticleRecombinant tissue plasminogen activator (rtPA)diterpene ginkgolides (DG)Ginkgo Biloba Extract (GBE)metabolomicsprefrontal cortexexcitotoxicityNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol Volume 14, Pp 1755-1772 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Recombinant tissue plasminogen activator (rtPA) diterpene ginkgolides (DG) Ginkgo Biloba Extract (GBE) metabolomics prefrontal cortex excitotoxicity Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Recombinant tissue plasminogen activator (rtPA) diterpene ginkgolides (DG) Ginkgo Biloba Extract (GBE) metabolomics prefrontal cortex excitotoxicity Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Chen Z Bai S Hu Q Shen P Wang T Liang Z Wang W Qi X Xie P Ginkgo biloba extract and its diterpene ginkgolide constituents ameliorate the metabolic disturbances caused by recombinant tissue plasminogen activator in rat prefrontal cortex
description	Zhi Chen,1–3,* Shunjie Bai,1–4,* Qingchuan Hu,1–4,* Peng Shen,2,3,5,* Ting Wang,2–4,* Zihong Liang,2,3,5,6,* Wei Wang,1–3 Xunzhong Qi,2,3,5 Peng Xie1,2,4–6 1Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing, China; 2Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China; 3Chongqing Key Laboratory of Neurobiology, Chongqing, China; 4Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing, China; 5Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 6Department of Neurology, The Inner Mongolia Autonomous Region People’s Hospital, Hohhot, Inner Mongolia, China *These authors contributed equally to this work Introduction: Although recombinant tissue plasminogen activator (rtPA) is a widely used therapy in patients with acute ischemic stroke, rtPA-induced toxicity or its adverse effects have been reported in our previous studies. However, Ginkgo biloba extract (GBE) may provide neuroprotective effects against rtPA-induced toxicity. Thus, in the present study, we investigated whether a single administration of rtPA caused neurotoxicity in the prefrontal cortex (PFC) of rats and determined whether GBE or its diterpene ginkgolide (DG) constituents were neuroprotective against any rtPA-induced toxicity. Materials and methods: We randomly divided adult Sprague-Dawley rats into four groups that were intravenously administered saline, rtPA, rtPA+DG, or rtPA+GBE. The rats were sacrificed 24 hours later and the whole brain removed. A gas chromatography–mass spectrometry metabolomic approach was used to detect molecular changes in the PFC among the groups. Multivariate statistical and pathway analyses were used to determine the relevant metabolites as well as their functions and pathways. Results: We found 32 metabolites differentially altered in the four groups that were primarily involved in neurotransmitter, amino acid, energy, lipid, and nucleotide metabolism. Our results indicated that a single rtPA administration caused metabolic disturbances in the PFC. Both GBE and DG effectively ameliorated these rtPA-induced disturbances, although DG better controlled the rtPA-induced glutamate and aspartate excitotoxicity and the activation of NMDA receptor. Conclusion: Our results provide important novel mechanistic insights into the adverse effects of rtPA and offer directions for future exploration on the thrombolytic effects of rtPA combined with the administration of DG or GBE for the treatment of acute ischemic stroke in humans. Keywords: recombinant tissue plasminogen activator (rtPA), diterpene ginkgolides (DG), Ginkgo biloba extract (GBE), metabolomics, prefrontal cortex, excitotoxicity
format	article
author	Chen Z Bai S Hu Q Shen P Wang T Liang Z Wang W Qi X Xie P
author_facet	Chen Z Bai S Hu Q Shen P Wang T Liang Z Wang W Qi X Xie P
author_sort	Chen Z
title	Ginkgo biloba extract and its diterpene ginkgolide constituents ameliorate the metabolic disturbances caused by recombinant tissue plasminogen activator in rat prefrontal cortex
title_short	Ginkgo biloba extract and its diterpene ginkgolide constituents ameliorate the metabolic disturbances caused by recombinant tissue plasminogen activator in rat prefrontal cortex
title_full	Ginkgo biloba extract and its diterpene ginkgolide constituents ameliorate the metabolic disturbances caused by recombinant tissue plasminogen activator in rat prefrontal cortex
title_fullStr	Ginkgo biloba extract and its diterpene ginkgolide constituents ameliorate the metabolic disturbances caused by recombinant tissue plasminogen activator in rat prefrontal cortex
title_full_unstemmed	Ginkgo biloba extract and its diterpene ginkgolide constituents ameliorate the metabolic disturbances caused by recombinant tissue plasminogen activator in rat prefrontal cortex
title_sort	ginkgo biloba extract and its diterpene ginkgolide constituents ameliorate the metabolic disturbances caused by recombinant tissue plasminogen activator in rat prefrontal cortex
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/a9c2c0ae405542dc8b22297a71c5b181
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Ginkgo biloba extract and its diterpene ginkgolide constituents ameliorate the metabolic disturbances caused by recombinant tissue plasminogen activator in rat prefrontal cortex

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