Acteoside alleviates blood-brain barrier damage induced by ischemic stroke through inhibiting microglia HMGB1/TLR4/NLRP3 signaling.
Biochem Pharmacol
; 220: 115968, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38104671
ABSTRACT
Ischemic stroke (IS) can cause severe harm, inducing oxidative stress, inflammation, and pyroptotic death. IS treatment efficacy remains limited, and microglia are important regulators of IS-related blood-brain barrier (BBB) damage. It is thus vital that new therapeutic agents capable of targeting microglia be identified to treat IS-related damage to the BBB. Acteoside (ACT), which is a compound derived from Cistanche tubulosa (Schenk) Wight., offers promising bioactivity, but its ability to protect against central nervous system injury remains to be documented. To clarify the protective benefits and mechanisms through which ACT can protect against damage to the BBB, a rat middle cerebral artery occlusion (MCAO) model system was herein employed. These in vivo analyses demonstrated that ACT was able to significantly reduce cerebral infarct size while improving their neurological scores and altering neurotrophic and inflammatory factor release. RNA sequencing and molecular docking studies highlighted the ability of ACT to exert its protective benefits via the HMGB1/TLR4/NLRP3 axis. Western immunoblotting and immunofluorescent staining for tight junction proteins additionally confirmed the ability of ACT to preserve BBB integrity. The underlying mechanisms were then explored with an oxygen-glucose deprivation (OGD) model in vitro with BV2 cells. This strategy thus confirmed that the ability of ACT to suppress microglial inflammatory and pyroptotic activity was HMGB1/TLR4/NLRP3 pathway-dependent. These data thus offer novel evidence that ACT can protect against IS-related damage to the BBB through the abrogation of inflammatory and pyroptotic activity, underscoring its promise as a novel lead compound for the therapeutic treatment of IS.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Traumatismo por Reperfusão
/
Isquemia Encefálica
/
Acidente Vascular Cerebral
/
Proteína HMGB1
/
Polifenóis
/
AVC Isquêmico
/
Glucosídeos
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article