Oxymatrine improves blood-brain barrier integrity after cerebral ischemia-reperfusion injury by downregulating CAV1 and MMP9 expression.
Alkaloids
/ pharmacology
Animals
Blood-Brain Barrier
/ drug effects
Brain Ischemia
/ pathology
Caveolin 1
/ genetics
Disease Models, Animal
Down-Regulation
/ drug effects
Matrix Metalloproteinase 9
/ metabolism
Mice, Inbred C57BL
Neuroprotective Agents
/ pharmacology
Permeability
Quinolizines
/ pharmacology
Reperfusion Injury
/ drug therapy
Sophora
/ chemistry
Blood-brain barrier
Caveolin-1
Ischemia-reperfusion injury
MMP-9
Oxymatrine
Journal
Phytomedicine : international journal of phytotherapy and phytopharmacology
ISSN: 1618-095X
Titre abrégé: Phytomedicine
Pays: Germany
ID NLM: 9438794
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
24
12
2020
revised:
20
01
2021
accepted:
06
02
2021
pubmed:
25
2
2021
medline:
2
6
2021
entrez:
24
2
2021
Statut:
ppublish
Résumé
Ischemic stroke (IS) is a major neurological condition associated with extremely high morbidity and mortality worldwide. Oxymatrine (OMT), a quinolizidine alkaloid extracted from the root of Sophora flavescens, has neuroprotective properties and protects against IS. However, whether its protective effect involves alterations in the integrity of the blood-brain barrier (BBB) is unknown. Here, we used in vivo and in vitro models of IS to evaluate the protective effects of OMT and to establish whether its effects are mediated via the modulation of the BBB function. We assessed the effects of OMT by using neurological function scores, triphenyltetrazolium chloride staining, Nissl staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling. OMT significantly prevented cellular damage, improved neurological function, and reduced BBB permeability in a mouse model of cerebral ischemia-reperfusion. Additionally, OMT protected the function of the tight junctions of bEend.3 cells against the consequences of oxygen-glucose deprivation. Furthermore, intracranial lentivirus injection of short hairpin RNA targeting Cav1 decreased caveolin-1 expression and inhibited the neuroprotective effects of OMT. OMT attenuated ischemia-reperfusion injury-induced damage to the BBB, and this neuroprotective action was at least partially dependent on the expression levels of CAV1 and MMP9 proteins. Therefore, OMT may offer effective protection against BBB injury induced by ischemia-reperfusion episodes.
Sections du résumé
BACKGROUND
BACKGROUND
Ischemic stroke (IS) is a major neurological condition associated with extremely high morbidity and mortality worldwide. Oxymatrine (OMT), a quinolizidine alkaloid extracted from the root of Sophora flavescens, has neuroprotective properties and protects against IS. However, whether its protective effect involves alterations in the integrity of the blood-brain barrier (BBB) is unknown.
PURPOSE
OBJECTIVE
Here, we used in vivo and in vitro models of IS to evaluate the protective effects of OMT and to establish whether its effects are mediated via the modulation of the BBB function.
METHODS
METHODS
We assessed the effects of OMT by using neurological function scores, triphenyltetrazolium chloride staining, Nissl staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling.
RESULTS
RESULTS
OMT significantly prevented cellular damage, improved neurological function, and reduced BBB permeability in a mouse model of cerebral ischemia-reperfusion. Additionally, OMT protected the function of the tight junctions of bEend.3 cells against the consequences of oxygen-glucose deprivation. Furthermore, intracranial lentivirus injection of short hairpin RNA targeting Cav1 decreased caveolin-1 expression and inhibited the neuroprotective effects of OMT.
CONCLUSIONS
CONCLUSIONS
OMT attenuated ischemia-reperfusion injury-induced damage to the BBB, and this neuroprotective action was at least partially dependent on the expression levels of CAV1 and MMP9 proteins. Therefore, OMT may offer effective protection against BBB injury induced by ischemia-reperfusion episodes.
Identifiants
pubmed: 33626426
pii: S0944-7113(21)00047-7
doi: 10.1016/j.phymed.2021.153505
pii:
doi:
Substances chimiques
Alkaloids
0
Cav1 protein, mouse
0
Caveolin 1
0
Neuroprotective Agents
0
Quinolizines
0
oxymatrine
85U4C366QS
Matrix Metalloproteinase 9
EC 3.4.24.35
Mmp9 protein, mouse
EC 3.4.24.35
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
153505Informations de copyright
Copyright © 2021. Published by Elsevier GmbH.