Limonin Attenuates LPS-Induced Hepatotoxicity by Inhibiting Pyroptosis via NLRP3/Gasdermin D Signaling Pathway.
J Agric Food Chem
; 69(3): 982-991, 2021 Jan 27.
Article
en En
| MEDLINE
| ID: mdl-33427450
Lipopolysaccharide (LPS)-induced liver injury is the main factor in acute liver failure. The current study aims to investigate the protection of limonin, an antioxidant compound from citrus fruit, against LPS-induced liver toxicity and elucidate the potential mechanisms. We found that limonin elevated cell viability and reduced LDH release in LPS-treated HepG2 cells. Limonin also inhibited LPS-induced pyroptosis by inhibiting membrane rupture, reducing ROS generation, and decreasing gasdermin D activation. Moreover, limonin inhibited the formation of a NOD-like receptor protein 3 (NLRP3)/Apoptosis-associated speck-like protein containing a CARD (ASC) complex by reducing the related protein expression and the colocalization cytosolic of NLRP3 and caspase-1 and then suppressed IL-1ß maturation. Ultimately, we established LPS-induced hepatotoxicity in vivo by using C57BL/6 mice administrated LPS (10 mg/kg) intraperitoneally and limonin (50 and 100 mg/kg) orally. We found that limonin dereased the serum ALT and AST activity and LDH release and increased the hepatic GSH amount in LPS-treated mice. Additionally, the liver histological evaluation revealed that limonin protects against LPS-induced liver damage. We further demonstrated that limonin ameliorated LPS-induced hepatotoxicity by inhibiting pyroptosis via the NLRP3/gasdermin D signaling pathway. In summary, this study uncovered the mechanism whereby limonin mitigated LPS-induced hepatotoxicity and documented that limonin might be a promising candidate drug for LPS-induced hepatotoxicity.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Proteínas de Unión a Fosfato
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Péptidos y Proteínas de Señalización Intracelular
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Enfermedad Hepática Inducida por Sustancias y Drogas
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Piroptosis
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Proteína con Dominio Pirina 3 de la Familia NLR
Tipo de estudio:
Etiology_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Agric Food Chem
Año:
2021
Tipo del documento:
Article