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Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway
Scutellarin is used to treat brain ischaemia. However, its underlying mechanism of action remains unclear. This study aimed to elucidate the potential mechanism of action of scutellarin in brain ischaemia through network pharmacology and experimental verification. The JAK2/STAT3 signalling pathway w...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10169761/ https://www.ncbi.nlm.nih.gov/pubmed/37160937 http://dx.doi.org/10.1038/s41598-023-33156-5 |
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author | Jia, Qiu-Ye Chen, Hao‑Lun Qi, Zhi Zhang, Xiao‑Li‑Na Zheng, Li-Yang Liu, Teng-Teng Yuan, Yun Yang, Li Wu, Chun‑Yun |
author_facet | Jia, Qiu-Ye Chen, Hao‑Lun Qi, Zhi Zhang, Xiao‑Li‑Na Zheng, Li-Yang Liu, Teng-Teng Yuan, Yun Yang, Li Wu, Chun‑Yun |
author_sort | Jia, Qiu-Ye |
collection | PubMed |
description | Scutellarin is used to treat brain ischaemia. However, its underlying mechanism of action remains unclear. This study aimed to elucidate the potential mechanism of action of scutellarin in brain ischaemia through network pharmacology and experimental verification. The JAK2/STAT3 signalling pathway was identified and experimentally verified. Expression of JAK2/STAT3 signalling related proteins in TNC-1 astrocytes with BV-2 microglia-conditioned medium (CM), CM + lipopolysaccharide (LPS) (CM + L), and CM pretreated with scutellarin + LPS (CM + SL) was analysed by Western Blot and immunofluorescence staining. Expression levels of JAK2, p-JAK2, STAT3, and p-STAT3 were evaluated in astrocytes pre-treated with AG490. Middle cerebral artery occlusion (MCAO) in rats was performed in different experimental groups to detect expression of the above biomarkers. Network pharmacology suggested that the JAK2/STAT3 signalling pathway is one of the mechanisms by which scutellarin mitigates cerebral ischaemic damage. In TNC-1 astrocytes, p-JAK2 and p-STAT3 expression were significantly up-regulated in the CM + L group. Scutellarin promoted the up-regulation of various markers and AG490 neutralised the effect of scutellarin. In vivo, up-regulation of p-JAK2 and p-STAT3 after ischaemia is known. These results are consistent with previous reports. Scutellarin further enhanced this upregulation at 1, 3, and 7 d after MCAO. Scutellarin exerts its therapeutic effects on cerebral ischaemia by activating the astrocyte JAK2/STAT3 signalling, which provides a firm experimental basis for its clinical application. |
format | Online Article Text |
id | pubmed-10169761 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-101697612023-05-11 Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway Jia, Qiu-Ye Chen, Hao‑Lun Qi, Zhi Zhang, Xiao‑Li‑Na Zheng, Li-Yang Liu, Teng-Teng Yuan, Yun Yang, Li Wu, Chun‑Yun Sci Rep Article Scutellarin is used to treat brain ischaemia. However, its underlying mechanism of action remains unclear. This study aimed to elucidate the potential mechanism of action of scutellarin in brain ischaemia through network pharmacology and experimental verification. The JAK2/STAT3 signalling pathway was identified and experimentally verified. Expression of JAK2/STAT3 signalling related proteins in TNC-1 astrocytes with BV-2 microglia-conditioned medium (CM), CM + lipopolysaccharide (LPS) (CM + L), and CM pretreated with scutellarin + LPS (CM + SL) was analysed by Western Blot and immunofluorescence staining. Expression levels of JAK2, p-JAK2, STAT3, and p-STAT3 were evaluated in astrocytes pre-treated with AG490. Middle cerebral artery occlusion (MCAO) in rats was performed in different experimental groups to detect expression of the above biomarkers. Network pharmacology suggested that the JAK2/STAT3 signalling pathway is one of the mechanisms by which scutellarin mitigates cerebral ischaemic damage. In TNC-1 astrocytes, p-JAK2 and p-STAT3 expression were significantly up-regulated in the CM + L group. Scutellarin promoted the up-regulation of various markers and AG490 neutralised the effect of scutellarin. In vivo, up-regulation of p-JAK2 and p-STAT3 after ischaemia is known. These results are consistent with previous reports. Scutellarin further enhanced this upregulation at 1, 3, and 7 d after MCAO. Scutellarin exerts its therapeutic effects on cerebral ischaemia by activating the astrocyte JAK2/STAT3 signalling, which provides a firm experimental basis for its clinical application. Nature Publishing Group UK 2023-05-09 /pmc/articles/PMC10169761/ /pubmed/37160937 http://dx.doi.org/10.1038/s41598-023-33156-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Jia, Qiu-Ye Chen, Hao‑Lun Qi, Zhi Zhang, Xiao‑Li‑Na Zheng, Li-Yang Liu, Teng-Teng Yuan, Yun Yang, Li Wu, Chun‑Yun Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway |
title | Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway |
title_full | Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway |
title_fullStr | Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway |
title_full_unstemmed | Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway |
title_short | Network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of JAK2/STAT3 signalling pathway |
title_sort | network pharmacology to explore the mechanism of scutellarin in the treatment of brain ischaemia and experimental verification of jak2/stat3 signalling pathway |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10169761/ https://www.ncbi.nlm.nih.gov/pubmed/37160937 http://dx.doi.org/10.1038/s41598-023-33156-5 |
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