Glycyrrhetinic acid triggers a protective autophagy by inhibiting the JAK2/STAT3 pathway in cerebral ischemia/reperfusion injury.
Neuroscience
; 554: 96-106, 2024 Aug 30.
Article
en En
| MEDLINE
| ID: mdl-38964451
ABSTRACT
Cerebral ischemia/reperfusion injury (CIRI) is a common feature of ischemic stroke leading to a poor prognosis. Effective treatments targeting I/R injury are still insufficient. The study aimed to investigate the mechanisms, by which glycyrrhizic acid (18ß-GA) in ameliorates CIRI. Our results showed that 18ß-GA significantly decreased the infarct volume, neurological deficit scores, and pathological changes in the brain tissue of rats after middle cerebral artery occlusion. Western blotting showed that 18ß-GA inhibited the expression levels of phosphorylated JAK2 and phosphorylated STAT3. Meanwhile, 18ß-GA increased LC3-II protein levels in a reperfusion duration-dependent manner, which was accompanied by an increase in the Bcl-2/Bax ratio. Inhibition of 18ß-GA-induced autophagy by 3-methyladenine (3-MA) enhanced apoptotic cell death. In addition, 18ß-GA inhibited the JAK2/STAT3 pathway, which was largely activated in response to oxygen-glucose deprivation/reoxygenation. However, the JAK2/STAT3 activator colivelin TFA abolished the inhibitory effect of 18ß-GA, suppressed autophagy, and significantly decreased the Bcl-2/Bax ratio. Taken together, these findings suggested that 18ß-GA pretreatment ameliorated CIRI partly by triggering a protective autophagy via the JAK2/STAT3 pathway. Therefore might be a potential drug candidate for treating ischemic stroke.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Autofagia
/
Daño por Reperfusión
/
Transducción de Señal
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Ratas Sprague-Dawley
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Fármacos Neuroprotectores
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Infarto de la Arteria Cerebral Media
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Factor de Transcripción STAT3
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Janus Quinasa 2
Límite:
Animals
Idioma:
En
Revista:
Neuroscience
Año:
2024
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos