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Limonin Attenuates LPS-Induced Hepatotoxicity by Inhibiting Pyroptosis via NLRP3/Gasdermin D Signaling Pathway
- Source :
- Journal of Agricultural and Food Chemistry. 69:982-991
- Publication Year :
- 2021
- Publisher :
- American Chemical Society (ACS), 2021.
-
Abstract
- 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-1β 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.
- Subjects :
- 0106 biological sciences
Liver injury
Antioxidant
Lipopolysaccharide
Limonin
medicine.medical_treatment
010401 analytical chemistry
Pyroptosis
General Chemistry
Glutathione
Pharmacology
medicine.disease
01 natural sciences
0104 chemical sciences
chemistry.chemical_compound
chemistry
medicine
Viability assay
Signal transduction
General Agricultural and Biological Sciences
010606 plant biology & botany
Subjects
Details
- ISSN :
- 15205118 and 00218561
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Journal of Agricultural and Food Chemistry
- Accession number :
- edsair.doi...........3359ed8654e55c966711854073a8a1e2