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Use network pharmacology methods to study the relationship between <jats:italic>E. breviscapus<\/jats:italic> (Vant.) Hand-Mazz. and ischemic stroke, predict the mechanism and active ingredients of <jats:italic>E. breviscapus<\/jats:italic> (Vant.) Hand-Mazz. in improving ischemic stroke disease. We study the protective effect of <jats:italic>E. breviscapus<\/jats:italic> injection on blood\u2013brain 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\u2013reperfusion injury has been prepared using the wire-suppository method. Firstly, the efficacy of <jats:italic>E. breviscapus<\/jats:italic> 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 <jats:italic>E. breviscapus<\/jats:italic> 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\u2013brain barrier function, so we chose the blood\u2013brain 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, <jats:italic>E. breviscapus<\/jats:italic> 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 <jats:italic>E. breviscapus<\/jats:italic> 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 <jats:italic>E. breviscapus<\/jats:italic> 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.<\/jats:p>","DOI":"10.1038\/s41598-021-97908-x","type":"journal-article","created":{"date-parts":[[2021,9,16]],"date-time":"2021-09-16T10:03:34Z","timestamp":1631786614000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Protective mechanism of Erigeron breviscapus injection on blood\u2013brain barrier injury induced by cerebral ischemia in rats"],"prefix":"10.1038","volume":"11","author":[{"given":"Guangli","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijun","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,16]]},"reference":[{"key":"97908_CR1","volume-title":"Ischemic cerebrovascular disease","author":"ZM Luo","year":"2011","unstructured":"Luo, Z. 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