Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia

Background and aim: Buyang Huanwu Decoction (BHD) is a traditional Chinese herbal medicine that is effective for treating cerebral ischemia (CI). However, the molecular mechanisms of BHD in CI have not been fully elucidated. In this study, we integrated the circular RNA (circRNA)-microRNA (miRNA)-me...

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Autores principales:	Bowei Chen, Jian Yi, Yaqian Xu, Piao Zheng, Rongmei Tang, Baiyan Liu
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2022
Materias:	Buyang Huanwu Decoction Cerebral ischemia CircRNA MiRNA CeRNA Neurovascular unit Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/6b4be71e6f5543499c61252a154a551f
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spelling	oai:doaj.org-article:6b4be71e6f5543499c61252a154a551f2021-11-28T04:28:11ZConstruction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia0753-332210.1016/j.biopha.2021.112445https://doaj.org/article/6b4be71e6f5543499c61252a154a551f2022-01-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S0753332221012312https://doaj.org/toc/0753-3322Background and aim: Buyang Huanwu Decoction (BHD) is a traditional Chinese herbal medicine that is effective for treating cerebral ischemia (CI). However, the molecular mechanisms of BHD in CI have not been fully elucidated. In this study, we integrated the circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) network of middle cerebral artery occlusion (MACO) rats treated with BHD. Methods: SD rats were randomly divided into a control group, model group, model+BHD group (2.5, 5, 10 g/kg) and model+butylphthalide (NBP) group (54 mg/kg). The neurological functions of the rats were evaluated by a modified neurological severity scoring (mNSS) system. Pathological lesions were assessed by Nissl staining, and the effects of BHD on neurovascular unit (NVU) associated protein microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP) and von Willebrand factor (VWF) were assessed by immunohistochemistry. CeRNA and miRNA microarrays were used to establish the circRNA, miRNA, and mRNA profiles. Finally, a circRNA-miRNA-mRNA ternary transcription network was constructed. Results: BHD improved the neurobehavioral test scores (P < 0.01) and the histopathological changes in ischemic brain tissue in MCAO rats. The expression of MAP2 and VWF decreased and the expression of GFAP increased in the ischemic side brain tissue of MCAO rats (P < 0.01), and treatment with BHD reversed the above changes (P < 0.01 or 0.05). We identified seven, three, and 86 significantly dysregulated circRNAs, miRNAs, and mRNAs, respectively, that were associated with the neuroprotective effects of BHD. Furthermore, bioinformatics analysis showed that these targets may exert therapeutic effects through multiple pathways, such as the VEGF and Hippo signaling pathways. Finally, we constructed a circRNA-miRNA-mRNA network. Conclusions: In brief, our study provides novel insights into ceRNA-mediated gene regulation in the progression of NVU after CI and the mechanism of action for BHD.Bowei ChenJian YiYaqian XuPiao ZhengRongmei TangBaiyan LiuElsevierarticleBuyang Huanwu DecoctionCerebral ischemiaCircRNAMiRNACeRNANeurovascular unitTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 145, Iss , Pp 112445- (2022)
institution	DOAJ
collection	DOAJ
language	EN
topic	Buyang Huanwu Decoction Cerebral ischemia CircRNA MiRNA CeRNA Neurovascular unit Therapeutics. Pharmacology RM1-950
spellingShingle	Buyang Huanwu Decoction Cerebral ischemia CircRNA MiRNA CeRNA Neurovascular unit Therapeutics. Pharmacology RM1-950 Bowei Chen Jian Yi Yaqian Xu Piao Zheng Rongmei Tang Baiyan Liu Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia
description	Background and aim: Buyang Huanwu Decoction (BHD) is a traditional Chinese herbal medicine that is effective for treating cerebral ischemia (CI). However, the molecular mechanisms of BHD in CI have not been fully elucidated. In this study, we integrated the circular RNA (circRNA)-microRNA (miRNA)-messenger RNA (mRNA) network of middle cerebral artery occlusion (MACO) rats treated with BHD. Methods: SD rats were randomly divided into a control group, model group, model+BHD group (2.5, 5, 10 g/kg) and model+butylphthalide (NBP) group (54 mg/kg). The neurological functions of the rats were evaluated by a modified neurological severity scoring (mNSS) system. Pathological lesions were assessed by Nissl staining, and the effects of BHD on neurovascular unit (NVU) associated protein microtubule-associated protein 2 (MAP2), glial fibrillary acidic protein (GFAP) and von Willebrand factor (VWF) were assessed by immunohistochemistry. CeRNA and miRNA microarrays were used to establish the circRNA, miRNA, and mRNA profiles. Finally, a circRNA-miRNA-mRNA ternary transcription network was constructed. Results: BHD improved the neurobehavioral test scores (P < 0.01) and the histopathological changes in ischemic brain tissue in MCAO rats. The expression of MAP2 and VWF decreased and the expression of GFAP increased in the ischemic side brain tissue of MCAO rats (P < 0.01), and treatment with BHD reversed the above changes (P < 0.01 or 0.05). We identified seven, three, and 86 significantly dysregulated circRNAs, miRNAs, and mRNAs, respectively, that were associated with the neuroprotective effects of BHD. Furthermore, bioinformatics analysis showed that these targets may exert therapeutic effects through multiple pathways, such as the VEGF and Hippo signaling pathways. Finally, we constructed a circRNA-miRNA-mRNA network. Conclusions: In brief, our study provides novel insights into ceRNA-mediated gene regulation in the progression of NVU after CI and the mechanism of action for BHD.
format	article
author	Bowei Chen Jian Yi Yaqian Xu Piao Zheng Rongmei Tang Baiyan Liu
author_facet	Bowei Chen Jian Yi Yaqian Xu Piao Zheng Rongmei Tang Baiyan Liu
author_sort	Bowei Chen
title	Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia
title_short	Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia
title_full	Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia
title_fullStr	Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia
title_full_unstemmed	Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia
title_sort	construction of a circrna-mirna-mrna network revealed the potential mechanism of buyang huanwu decoction in the treatment of cerebral ischemia
publisher	Elsevier
publishDate	2022
url	https://doaj.org/article/6b4be71e6f5543499c61252a154a551f
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Construction of a circRNA-miRNA-mRNA network revealed the potential mechanism of Buyang Huanwu Decoction in the treatment of cerebral ischemia

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