Myricanol attenuates sepsis-induced inflammatory responses by nuclear factor erythroid 2-related factor 2 signaling and nuclear factor kappa B/mitogen-activated protein kinase pathway via upregulating Sirtuin 1.
Inflammopharmacology
; 32(3): 1887-1901, 2024 Jun.
Article
em En
| MEDLINE
| ID: mdl-38526770
ABSTRACT
Sepsis, a life-threatening condition characterized by dysregulated immune responses, remains a significant clinical challenge. Myricanol, a natural compound, plays a variety of roles in regulating lipid metabolism, anti-cancer, anti-neurodegeneration, and it could act as an Sirtuin 1 (SIRT1) activator. This study aimed to explore the therapeutic potential and underlying mechanism of myricanol in the lipopolysaccharide (LPS)-induced sepsis model. In vivo studies revealed that myricanol administration significantly improved the survival rate of LPS-treated mice, effectively mitigating LPS-induced inflammatory responses in lung tissue. Furthermore, in vitro studies demonstrated that myricanol treatment inhibited the expression of pro-inflammatory cytokines, attenuated signal pathway activation, and reduced oxidative stress in macrophages. In addition, we demonstrated that myricanol selectively enhances SIRT1 activation in LPS-stimulated macrophages, and all of the protective effect of myricanol were reversed through SIRT1 silencing. Remarkably, the beneficial effects of myricanol against LPS-induced sepsis were abolished in SIRT1 myeloid-specific knockout mice, underpinning the critical role of SIRT1 in mediating myricanol's therapeutic efficacy. In summary, this study provides significant evidence that myricanol acts as a potent SIRT1 activator, targeting inflammatory signal pathways and oxidative stress to suppress excessive inflammatory responses. Our findings highlight the potential of myricanol as a novel therapeutic agent for the treatment of LPS-induced sepsis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Regulação para Cima
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Lipopolissacarídeos
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NF-kappa B
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Camundongos Knockout
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Sepse
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Fator 2 Relacionado a NF-E2
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Sirtuína 1
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Inflamação
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Camundongos Endogâmicos C57BL
Limite:
Animals
Idioma:
En
Revista:
Inflammopharmacology
Assunto da revista:
FARMACOLOGIA
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TERAPIA POR MEDICAMENTOS
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China