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Eur J Pharmacol ; 949: 175717, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-37054938

RESUMO

An ischemic stroke usually causes blood-brain barrier (BBB) damage and excessive oxidative stress (OS) levels. Kinsenoside (KD), a major effective compound extracted in Chinese herbal medicine Anoectochilus roxburghii (Orchidaceae), has anti-OS effects. The present study focused on exploring KD's protection against OS-mediated cerebral endothelial cell damage and BBB damage within the mouse model. Intracerebroventricular administration of KD upon reperfusion after 1 h ischemia decreased infarct volumes, neurological deficit, brain edema, neuronal loss, and apoptosis 72 h post-ischemic stroke. KD improved BBB structure and function, as evidenced by a lower 18F-fluorodeoxyglucose pass rate of the BBB and upregulation of tight junction (TJ) proteins such as occludin, claudin-5, and zonula occludens-1 (ZO-1). KD protected bEnd.3 endothelial cells from oxygen and glucose deprivation/reoxygenation (OGD/R) injury in an in-vitro study. Meanwhile, OGD/R reduced transepithelial electronic resistance, whereas KD significantly increased TJ protein levels. Furthermore, based on in-vivo and in-vitro research, KD alleviated OS in endothelial cells, which is related to nuclear factor, erythroid 2 like 2 (Nrf2) nuclear translocation as well as Nrf2/haem oxygenase 1 signaling protein stimulation. Our findings demonstrated that KD might serve as a potential compound for treating ischemic stroke involving antioxidant mechanisms.


Assuntos
AVC Isquêmico , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Camundongos , Animais , Barreira Hematoencefálica/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , AVC Isquêmico/metabolismo , Células Endoteliais , Estresse Oxidativo , Proteínas de Junções Íntimas/metabolismo , Oxigênio/metabolismo , Glucose/metabolismo , Traumatismo por Reperfusão/metabolismo , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/metabolismo
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