Salvianolic acid B improves mitochondrial dysfunction of septic cardiomyopathy via enhancing ATF5-mediated mitochondrial unfolded protein response.
Toxicol Appl Pharmacol
; 491: 117072, 2024 Oct.
Article
em En
| MEDLINE
| ID: mdl-39153513
ABSTRACT
AIMS:
Septic cardiomyopathy is characterized by impaired contractile function and mitochondrial activity dysregulation. Salvianolic acid B (Sal B) is a potent therapeutic compound derived from the traditional Chinese medicine Salvia miltiorrhiza. This study explored the protective effects of Sal B on septic heart injury, emphasizing the mitochondrial unfolded protein response (UPRmt). MATERIALS ANDMETHODS:
An in vivo mouse model of lipopolysaccharide (LPS)-induced heart injury was utilized to assess Sal B's protective role in septic cardiomyopathy. Additionally, cell models stimulated by LPS were developed to investigate the mechanisms of Sal B on UPRmt. Quantitative polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence were employed for molecular analysis.RESULTS:
Sal B, administered at doses of 10, 30, and 60 mg/kg, demonstrated protective effects on cardiac contractile function, reduced heart inflammation, and mitigated cardiac injury in LPS-exposed mice. In cardiomyocytes, LPS induced apoptosis, elevated mitochondrial ROS levels, promoted mitochondrial fission, and decreased mitochondrial membrane potential, all of which were alleviated by Sal B. Mechanistically, Sal B was found to induce UPRmt both in vivo and in vitro. ATF5, identified as a UPRmt activator, was modulated by LPS and Sal B, resulting in increased ATF5 expression and its translocation from the cytosol to the nucleus. ATF5-siRNA delivery reversed UPRmt upregulation, exacerbating mitochondrial dysfunction in LPS-stimulated cardiomyocytes and counteracting the mitochondrial function enhancement in Sal B-treated cardiomyocytes.CONCLUSIONS:
This study provides evidence that Sal B confers cardiac protection by enhancing UPRmt, highlighting its potential as a therapeutic approach for mitigating mitochondrial dysfunction in septic cardiomyopathy.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Benzofuranos
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Miócitos Cardíacos
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Resposta a Proteínas não Dobradas
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Camundongos Endogâmicos C57BL
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Mitocôndrias Cardíacas
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Cardiomiopatias
Limite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article