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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Guangli Liu ◽  
Yan Liang ◽  
Min Xu ◽  
Ming Sun ◽  
Weijun Sun ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Protein Expression ◽  
Signaling Pathway ◽  
Brain Tissue ◽  
Blood Brain Barrier ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Brain Barrier ◽  
Blood Brain ◽  
Dicaffeoylquinic Acid

AbstractThis 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.

scholarly journals Oxymatrine Improves the Integrity of the Blood-Brain Barrier after Cerebral Ischemia-Reperfusion Injury through the Caveolin-1/MMP-9 Signaling Pathway

2020 ◽  
Author(s):  
Jiaoyan Yu ◽  
Qingqing Liu ◽  
Xi Li ◽  
Mei Zhao ◽  
Ting Sun ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Blood Brain Barrier ◽  
Ischemia Reperfusion ◽  
Neurological Function ◽  
Brain Barrier ◽  
High Morbidity ◽  
Cerebral Ischemia Reperfusion ◽  
Blood Brain

Abstract BackgroundIschemic stroke (IS) is a major neurological disease worldwide and is associated with extremely high morbidity and mortality. Oxymatrine (OMT) has neuroprotective properties and protects against IS. However, whether its protective effect involves the blood-brain barrier (BBB) integrity is unknown.MethodsHere, we used in vivo and in vitro models of IS to evaluate the protective effect of OMT and its mechanism with regard to the BBB. We assayed the role of OMT using neurological function scores and triphenyltetrazolium chloride, Nissl, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining.ResultsOMT significantly improved the neurological function and brain state and reduced BBB permeability in a mouse model of cerebral ischemia-reperfusion. Additionally, OMT improved the tight junction of bEend.3 cells under oxygen-glucose deprivation. Moreover, intracranial lentivirus injection-induced Cav-1 knockdown reduced the neuroprotective effects of OMT.ConclusionsOMT could improve I/R injury-induced damage to the BBB, and its effects may be related to the regulation of the Cav-1/MMP-9 signaling pathway. This suggests that OMT may offer effective protection against BBB injury after I/R.

scholarly journals Oxymatrine Improves the Integrity of the Blood-brain Barrier After Cerebral Ischemia-reperfusion Injury Through the Caveolin-1/MMP-9 Signaling Pathway

2020 ◽  
Author(s):  
Jiaoyan Yu ◽  
Qingqing Lu ◽  
Xi Li ◽  
Mei Zhao ◽  
Ting Sun ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Protective Effect ◽  
Signaling Pathway ◽  
Blood Brain Barrier ◽  
Ischemia Reperfusion ◽  
Brain Barrier ◽  
Brain State ◽  
High Morbidity ◽  
Cerebral Ischemia Reperfusion ◽  
Blood Brain

Abstract Ischemic stroke (IS) is a major neurological disease worldwide and is associated with extremely high morbidity and mortality. Oxymatrine (OMT) has neuroprotective properties and protects against IS. However, whether its protective effect involves the blood-brain barrier (BBB) integrity is unknown. In this study, we used in vivo and in vitro models of IS to evaluate the protective effect of OMT and its mechanism with regard to the BBB. Our results showed that OMT significantly improved the neurological function and brain state and reduced BBB permeability in a mouse model of cerebral ischemia-reperfusion. Additionally, OMT improved the tight junction of bEend.3 cells under oxygen-glucose deprivation. Moreover, intracranial lentivirus injection-induced Cav-1 knockdown reduced the neuroprotective effects of OMT. Our results indicated that OMT could improve cI/R injury-induced damage to the BBB, and its effects may be related to the regulation of the Cav-1/MMP-9 signaling pathway. This suggests that OMT may offer effective protection against BBB injury after cI/R.

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