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Gualou Guizhi decoction promotes therapeutic angiogenesis via the miR210/HIF/VEGF pathway in vivo and in vitro
CONTEXT: Gualou Guizhi decoction (GLGZD) is an ancient Chinese classical prescription widely used to treat ischemic stroke. However, the molecular mechanisms of GLGZD promoting angiogenesis are unavailable. OBJECTIVE: This study investigates the angiogenesis effect of GLGZD as well as its mechanism....
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171115/ https://www.ncbi.nlm.nih.gov/pubmed/37158290 http://dx.doi.org/10.1080/13880209.2023.2204142 |
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author | Zhang, Yuqin Cao, Yajun Li, Yan Xiao, Lijuan Xu, Wei Xu, Wen Huang, Mei Zhang, Xiaoqin Chen, Yaping Nan, Lihong |
author_facet | Zhang, Yuqin Cao, Yajun Li, Yan Xiao, Lijuan Xu, Wei Xu, Wen Huang, Mei Zhang, Xiaoqin Chen, Yaping Nan, Lihong |
author_sort | Zhang, Yuqin |
collection | PubMed |
description | CONTEXT: Gualou Guizhi decoction (GLGZD) is an ancient Chinese classical prescription widely used to treat ischemic stroke. However, the molecular mechanisms of GLGZD promoting angiogenesis are unavailable. OBJECTIVE: This study investigates the angiogenesis effect of GLGZD as well as its mechanism. MATERIALS AND METHODS: Ischemic stroke was established by middle cerebral artery occlusion/reperfusion (MCAO/R) in male Sprague-Dawley (SD) rats. The GLGZD groups received GLGZD (3.6, 7.2 and 14.4 g/kg) orally. Oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed in HUVECs receiving GLGZD medicated serum (MS). MRI, H&E staining, qRT-PCR, western blot and immunofluorescence methods were employed. miRNA210 inhibitor was employed to confirm the effects of GLGZD on promoting angiogenesis. Dual luciferase assay was used to verify the binding of miRNA210 with HIF mRNA. RESULTS: GLGZD treatment improved neurological function (by 27%), alleviated neuronal injury (by 76%), reduced infarct volume (by 74%) and increased microvessel density (by fourfold) in vivo. In vitro data had also shown that GLGZD caused proliferation of the cells (by 58%), their migration, and eventual formation of tubes (by threefold). Simultaneously, GLGZD enhanced the levels of angiogenesis-related molecules and activated the HIF/VEGF signalling pathway. Surprisingly, the beneficial effects of GLGZD on post-stroke angiogenesis and neurological recovery were weakened by miRNA210 inhibitor, and also abolished the mediation of proangiogenic factors. miRNA210 directly targeted HIF mRNA. DISCUSSION AND CONCLUSIONS: GLGZD enhances angiogenesis via activation of the miRNA210/HIF/VEGF signalling pathway, suggesting it can be a novel application as an effective angiogenic formula for stroke recovery. |
format | Online Article Text |
id | pubmed-10171115 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-101711152023-05-11 Gualou Guizhi decoction promotes therapeutic angiogenesis via the miR210/HIF/VEGF pathway in vivo and in vitro Zhang, Yuqin Cao, Yajun Li, Yan Xiao, Lijuan Xu, Wei Xu, Wen Huang, Mei Zhang, Xiaoqin Chen, Yaping Nan, Lihong Pharm Biol Research Article CONTEXT: Gualou Guizhi decoction (GLGZD) is an ancient Chinese classical prescription widely used to treat ischemic stroke. However, the molecular mechanisms of GLGZD promoting angiogenesis are unavailable. OBJECTIVE: This study investigates the angiogenesis effect of GLGZD as well as its mechanism. MATERIALS AND METHODS: Ischemic stroke was established by middle cerebral artery occlusion/reperfusion (MCAO/R) in male Sprague-Dawley (SD) rats. The GLGZD groups received GLGZD (3.6, 7.2 and 14.4 g/kg) orally. Oxygen-glucose deprivation/reoxygenation (OGD/R) model was constructed in HUVECs receiving GLGZD medicated serum (MS). MRI, H&E staining, qRT-PCR, western blot and immunofluorescence methods were employed. miRNA210 inhibitor was employed to confirm the effects of GLGZD on promoting angiogenesis. Dual luciferase assay was used to verify the binding of miRNA210 with HIF mRNA. RESULTS: GLGZD treatment improved neurological function (by 27%), alleviated neuronal injury (by 76%), reduced infarct volume (by 74%) and increased microvessel density (by fourfold) in vivo. In vitro data had also shown that GLGZD caused proliferation of the cells (by 58%), their migration, and eventual formation of tubes (by threefold). Simultaneously, GLGZD enhanced the levels of angiogenesis-related molecules and activated the HIF/VEGF signalling pathway. Surprisingly, the beneficial effects of GLGZD on post-stroke angiogenesis and neurological recovery were weakened by miRNA210 inhibitor, and also abolished the mediation of proangiogenic factors. miRNA210 directly targeted HIF mRNA. DISCUSSION AND CONCLUSIONS: GLGZD enhances angiogenesis via activation of the miRNA210/HIF/VEGF signalling pathway, suggesting it can be a novel application as an effective angiogenic formula for stroke recovery. Taylor & Francis 2023-05-09 /pmc/articles/PMC10171115/ /pubmed/37158290 http://dx.doi.org/10.1080/13880209.2023.2204142 Text en © 2023 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent. |
spellingShingle | Research Article Zhang, Yuqin Cao, Yajun Li, Yan Xiao, Lijuan Xu, Wei Xu, Wen Huang, Mei Zhang, Xiaoqin Chen, Yaping Nan, Lihong Gualou Guizhi decoction promotes therapeutic angiogenesis via the miR210/HIF/VEGF pathway in vivo and in vitro |
title | Gualou Guizhi decoction promotes therapeutic angiogenesis via the miR210/HIF/VEGF pathway in vivo and in vitro |
title_full | Gualou Guizhi decoction promotes therapeutic angiogenesis via the miR210/HIF/VEGF pathway in vivo and in vitro |
title_fullStr | Gualou Guizhi decoction promotes therapeutic angiogenesis via the miR210/HIF/VEGF pathway in vivo and in vitro |
title_full_unstemmed | Gualou Guizhi decoction promotes therapeutic angiogenesis via the miR210/HIF/VEGF pathway in vivo and in vitro |
title_short | Gualou Guizhi decoction promotes therapeutic angiogenesis via the miR210/HIF/VEGF pathway in vivo and in vitro |
title_sort | gualou guizhi decoction promotes therapeutic angiogenesis via the mir210/hif/vegf pathway in vivo and in vitro |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10171115/ https://www.ncbi.nlm.nih.gov/pubmed/37158290 http://dx.doi.org/10.1080/13880209.2023.2204142 |
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