Therapeutic effects of JLX-001 on ischemic stroke by inducing autophagy via AMPK-ULK1 signaling pathway in rats.
Brain Res Bull
; 153: 162-170, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31472184
ABSTRACT
(3ß,5α,16α,20S)-4,4,14-trimethyl-3,20-bis(methylamino)-9,19-cyclopregnan-16-ol-dihydrochloride (JLX-001), a structural analogue of cyclovirobuxine D (CVB-D), is a novel compound from synthesis. This study aims to confirm the therapeutic effects of JLX001 on ischemic stroke (IS) and research its induction of autophagy function via 5'-AMP-activated protein kinase (AMPK)-Human Serine/threonine-protein kinase (ULK1) signaling pathway activation. The therapeutic effects of JLX001 were evaluated by infarct sizes, brain edema, neurological scores and proportion of apoptotic neurons in Sprague-Dawley (SD) rats with middle cerebral artery occlusion/reperfusion (MCAO/R). The number of autophagosomes was obtained by transmission electron microscopy. The expression of LC3-II was measured by immunofluorescence. p-AMPK and activated ULK1 were detected by western blots. Results showed that JLX001 treatment markedly alleviated cerebral infarcts, edema, neurological scores and proportion of apoptotic neurons in MCAO/R rats. The number of autophagosomes was increased, accompanying with the increased expressions of LC3-II, p-AMPK and ULK1. In summary, JLX001 attenuates cerebral ischemia injury and the underlying mechanisms may relate to inducing autophagy via AMPK-ULK1 signaling pathway activation.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
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Triterpenos
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Isquemia Encefálica
Limite:
Animals
Idioma:
En
Revista:
Brain Res Bull
Ano de publicação:
2019
Tipo de documento:
Article