Protective mechanism of Erigeron breviscapus injection on blood–brain barrier injury induced by cerebral ischemia in rats

Abstract This study investigates the protective effect of Erigeron breviscapus injection, a classic traditional Chinese medicine most typically used by Chinese minority to treat stroke, on cerebral ischemia–reperfusion injury and the related signaling pathways. Use network pharmacology methods to st...

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Autores principales:	Guangli Liu, Yan Liang, Min Xu, Ming Sun, Weijun Sun, You Zhou, Xiaojuan Huang, Wenjie Song, Yuan Liang, Zhang Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c75982a220674409aee4591e05370745
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spelling	oai:doaj.org-article:c75982a220674409aee4591e053707452021-12-02T18:33:46ZProtective mechanism of Erigeron breviscapus injection on blood–brain barrier injury induced by cerebral ischemia in rats10.1038/s41598-021-97908-x2045-2322https://doaj.org/article/c75982a220674409aee4591e053707452021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-97908-xhttps://doaj.org/toc/2045-2322Abstract This study investigates the protective effect of Erigeron breviscapus injection, a classic traditional Chinese medicine most typically used by Chinese minority to treat stroke, on cerebral ischemia–reperfusion injury and the related signaling pathways. Use network pharmacology methods to study the relationship between E. breviscapus (Vant.) Hand-Mazz. and ischemic stroke, predict the mechanism and active ingredients of E. breviscapus (Vant.) Hand-Mazz. in improving ischemic stroke disease. We study the protective effect of E. breviscapus injection on blood–brain barrier (BBB) injuries induced by cerebral ischemia in rats by regulating the ROS/RNS-MMPs-TJs signaling pathway. The rat model of focal cerebral ischemia–reperfusion injury has been prepared using the wire-suppository method. Firstly, the efficacy of E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid in protecting BBB injury caused by cerebral ischemia has been evaluated. Secondly, the following two methods have been used to study the mechanism of E. breviscapus injection in regulating the ROS/RNS-MMPS-TJS signaling pathway: real-time PCR and western blot for the determination of iNOS, MMP-9, claudin-5, occludin, ZO-1 mRNA and protein expression in brain tissue. We find that PI3K-Akt signaling pathway predicted by network pharmaology affects the blood–brain barrier function, so we chose the blood–brain barrier-related MMP-9, claudin-5, iNOS, occludin and ZO-1 proteins are used for research. The results of our research show that 3 drugs can reduce the rate of cerebral infarction in rats, relieve the abnormal neuroethology of rats, reduce the degree of brain tissue lesion, increase the number of the Nissl corpuscle cells and repair the neuron ultrastructure in injured rats. At the same time, it can obviously reduce the ultrastructure damage of the BBB in rats. All three drugs significantly reduced the content of Evans blue in the ischemic brain tissue caused by cerebral ischemia in rats with BBB injury. In addition, E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid can decrease the protein expression of iNOS and MMP-9 in rat ischemic brain tissue. In addition, 3,5-dicaffeoylquinic acid can increase the protein expression of claudin-5. We conclude that E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid have obvious therapeutic effects on BBB and neuron injury induced by cerebral ischemia in rats. Our results from studying the mechanism of action show that E. breviscapus injection and Scutellarin inhibited the activation of MMP-9 by inhibiting the synthesis of iNOS, 3,5-dicaffeoylquinic acid inhibits the expression and activation of MMP-9 by inhibiting the activation of iNOS and reducing the generation of free radicals, thus reducing the degradation of important cytoskeleton connexin claudin-5 in the tight junction (TJ) structure by inhibiting the expression and activation of MMP-9. Finally BBB structure integrity was protected.Guangli LiuYan LiangMin XuMing SunWeijun SunYou ZhouXiaojuan HuangWenjie SongYuan LiangZhang WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-23 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Guangli Liu Yan Liang Min Xu Ming Sun Weijun Sun You Zhou Xiaojuan Huang Wenjie Song Yuan Liang Zhang Wang Protective mechanism of Erigeron breviscapus injection on blood–brain barrier injury induced by cerebral ischemia in rats
description	Abstract This study investigates the protective effect of Erigeron breviscapus injection, a classic traditional Chinese medicine most typically used by Chinese minority to treat stroke, on cerebral ischemia–reperfusion injury and the related signaling pathways. Use network pharmacology methods to study the relationship between E. breviscapus (Vant.) Hand-Mazz. and ischemic stroke, predict the mechanism and active ingredients of E. breviscapus (Vant.) Hand-Mazz. in improving ischemic stroke disease. We study the protective effect of E. breviscapus injection on blood–brain barrier (BBB) injuries induced by cerebral ischemia in rats by regulating the ROS/RNS-MMPs-TJs signaling pathway. The rat model of focal cerebral ischemia–reperfusion injury has been prepared using the wire-suppository method. Firstly, the efficacy of E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid in protecting BBB injury caused by cerebral ischemia has been evaluated. Secondly, the following two methods have been used to study the mechanism of E. breviscapus injection in regulating the ROS/RNS-MMPS-TJS signaling pathway: real-time PCR and western blot for the determination of iNOS, MMP-9, claudin-5, occludin, ZO-1 mRNA and protein expression in brain tissue. We find that PI3K-Akt signaling pathway predicted by network pharmaology affects the blood–brain barrier function, so we chose the blood–brain barrier-related MMP-9, claudin-5, iNOS, occludin and ZO-1 proteins are used for research. The results of our research show that 3 drugs can reduce the rate of cerebral infarction in rats, relieve the abnormal neuroethology of rats, reduce the degree of brain tissue lesion, increase the number of the Nissl corpuscle cells and repair the neuron ultrastructure in injured rats. At the same time, it can obviously reduce the ultrastructure damage of the BBB in rats. All three drugs significantly reduced the content of Evans blue in the ischemic brain tissue caused by cerebral ischemia in rats with BBB injury. In addition, E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid can decrease the protein expression of iNOS and MMP-9 in rat ischemic brain tissue. In addition, 3,5-dicaffeoylquinic acid can increase the protein expression of claudin-5. We conclude that E. breviscapus injection, Scutellarin and 3,5-dicaffeoylquinic acid have obvious therapeutic effects on BBB and neuron injury induced by cerebral ischemia in rats. Our results from studying the mechanism of action show that E. breviscapus injection and Scutellarin inhibited the activation of MMP-9 by inhibiting the synthesis of iNOS, 3,5-dicaffeoylquinic acid inhibits the expression and activation of MMP-9 by inhibiting the activation of iNOS and reducing the generation of free radicals, thus reducing the degradation of important cytoskeleton connexin claudin-5 in the tight junction (TJ) structure by inhibiting the expression and activation of MMP-9. Finally BBB structure integrity was protected.
format	article
author	Guangli Liu Yan Liang Min Xu Ming Sun Weijun Sun You Zhou Xiaojuan Huang Wenjie Song Yuan Liang Zhang Wang
author_facet	Guangli Liu Yan Liang Min Xu Ming Sun Weijun Sun You Zhou Xiaojuan Huang Wenjie Song Yuan Liang Zhang Wang
author_sort	Guangli Liu
title	Protective mechanism of Erigeron breviscapus injection on blood–brain barrier injury induced by cerebral ischemia in rats
title_short	Protective mechanism of Erigeron breviscapus injection on blood–brain barrier injury induced by cerebral ischemia in rats
title_full	Protective mechanism of Erigeron breviscapus injection on blood–brain barrier injury induced by cerebral ischemia in rats
title_fullStr	Protective mechanism of Erigeron breviscapus injection on blood–brain barrier injury induced by cerebral ischemia in rats
title_full_unstemmed	Protective mechanism of Erigeron breviscapus injection on blood–brain barrier injury induced by cerebral ischemia in rats
title_sort	protective mechanism of erigeron breviscapus injection on blood–brain barrier injury induced by cerebral ischemia in rats
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c75982a220674409aee4591e05370745
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Protective mechanism of Erigeron breviscapus injection on blood–brain barrier injury induced by cerebral ischemia in rats

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