Qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncRNA GAS5/miR-137 signaling pathway

Background: Ischemic stroke is the second leading cause of death and disability worldwide, which needs to develop new pharmaceuticals for its prevention and treatment. Qingda granule (QDG), a traditional Chinese medicine formulation, could improve angiotensin II-induced brain injury and decrease sys...

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Autores principales: Zhang, Ling, Cai, Qiaoyan, Lin, Shan, Chen, Bin, Jia, Beibei, Ye, Renzhi, Weygant, Nathaniel, Chu, Jianfeng, Peng, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2021
Materias:
Research Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976574/
https://www.ncbi.nlm.nih.gov/pubmed/33746585
http://dx.doi.org/10.7150/ijms.53603
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author Zhang, Ling
Cai, Qiaoyan
Lin, Shan
Chen, Bin
Jia, Beibei
Ye, Renzhi
Weygant, Nathaniel
Chu, Jianfeng
Peng, Jun
author_facet Zhang, Ling
Cai, Qiaoyan
Lin, Shan
Chen, Bin
Jia, Beibei
Ye, Renzhi
Weygant, Nathaniel
Chu, Jianfeng
Peng, Jun
author_sort Zhang, Ling
collection PubMed
description Background: Ischemic stroke is the second leading cause of death and disability worldwide, which needs to develop new pharmaceuticals for its prevention and treatment. Qingda granule (QDG), a traditional Chinese medicine formulation, could improve angiotensin II-induced brain injury and decrease systemic inflammation. In this study, we aimed to evaluate the neuroprotective effect of QDG against ischemia/reperfusion-induced cerebral injury and illustrate the potential mechanisms. Methods: The middle cerebral artery occlusion/reperfusion (MCAO/R) surgery in vivo and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro models were established. Ischemic infarct volume was quantified using magnetic resonance imaging (MRI). Neurobehavioral deficits were assessed using a five-point scale. Cerebral histopathology was determined by hematoxylin-eosin (HE) staining. Neuronal apoptosis was evaluated by TUNEL and immunostaining with NeuN antibodies. The protective effect of QDG on OGD/R-injured HT22 cells was determined by MTT assay and Hoechst 33258 staining. The expression of lncRNA GAS5, miR-137 and apoptosis-related proteins were investigated in MCAO/R-injured rats and in OGD/R-injured HT22 cells using RT-qPCR and western blot analysis. Results: QDG significantly reduced the ischemic infarct volume, which was accompanied with improvements in neurobehavioral deficits. Additionally, QDG significantly ameliorated cerebral histopathological changes and reduced neuron loss in MCAO/R-injured rats. Moreover, QDG improved growth and inhibited apoptosis of HT22 cells injured by OGD/R in vitro. Finally, QDG significantly decreased the expression of lncRNA GAS5, Bax and cleaved caspase3, whereas it increased miR-137 and Bcl-2 expression in MCAO/R-injured rats and in OGD/R-injured HT22 cells. Conclusion: QDG plays a neuroprotective role in ischemic stroke via regulation of the lncRNA GAS5/miR-137 signaling pathway.
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spelling pubmed-79765742021-03-19 Qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncRNA GAS5/miR-137 signaling pathway Zhang, Ling Cai, Qiaoyan Lin, Shan Chen, Bin Jia, Beibei Ye, Renzhi Weygant, Nathaniel Chu, Jianfeng Peng, Jun Int J Med Sci Research Paper Background: Ischemic stroke is the second leading cause of death and disability worldwide, which needs to develop new pharmaceuticals for its prevention and treatment. Qingda granule (QDG), a traditional Chinese medicine formulation, could improve angiotensin II-induced brain injury and decrease systemic inflammation. In this study, we aimed to evaluate the neuroprotective effect of QDG against ischemia/reperfusion-induced cerebral injury and illustrate the potential mechanisms. Methods: The middle cerebral artery occlusion/reperfusion (MCAO/R) surgery in vivo and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro models were established. Ischemic infarct volume was quantified using magnetic resonance imaging (MRI). Neurobehavioral deficits were assessed using a five-point scale. Cerebral histopathology was determined by hematoxylin-eosin (HE) staining. Neuronal apoptosis was evaluated by TUNEL and immunostaining with NeuN antibodies. The protective effect of QDG on OGD/R-injured HT22 cells was determined by MTT assay and Hoechst 33258 staining. The expression of lncRNA GAS5, miR-137 and apoptosis-related proteins were investigated in MCAO/R-injured rats and in OGD/R-injured HT22 cells using RT-qPCR and western blot analysis. Results: QDG significantly reduced the ischemic infarct volume, which was accompanied with improvements in neurobehavioral deficits. Additionally, QDG significantly ameliorated cerebral histopathological changes and reduced neuron loss in MCAO/R-injured rats. Moreover, QDG improved growth and inhibited apoptosis of HT22 cells injured by OGD/R in vitro. Finally, QDG significantly decreased the expression of lncRNA GAS5, Bax and cleaved caspase3, whereas it increased miR-137 and Bcl-2 expression in MCAO/R-injured rats and in OGD/R-injured HT22 cells. Conclusion: QDG plays a neuroprotective role in ischemic stroke via regulation of the lncRNA GAS5/miR-137 signaling pathway. Ivyspring International Publisher 2021-02-06 /pmc/articles/PMC7976574/ /pubmed/33746585 http://dx.doi.org/10.7150/ijms.53603 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Zhang, Ling
Cai, Qiaoyan
Lin, Shan
Chen, Bin
Jia, Beibei
Ye, Renzhi
Weygant, Nathaniel
Chu, Jianfeng
Peng, Jun
Qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncRNA GAS5/miR-137 signaling pathway
title Qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncRNA GAS5/miR-137 signaling pathway
title_full Qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncRNA GAS5/miR-137 signaling pathway
title_fullStr Qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncRNA GAS5/miR-137 signaling pathway
title_full_unstemmed Qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncRNA GAS5/miR-137 signaling pathway
title_short Qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncRNA GAS5/miR-137 signaling pathway
title_sort qingda granule exerts neuroprotective effects against ischemia/reperfusion-induced cerebral injury via lncrna gas5/mir-137 signaling pathway
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7976574/
https://www.ncbi.nlm.nih.gov/pubmed/33746585
http://dx.doi.org/10.7150/ijms.53603
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