Gentiopicroside improves NASH and liver fibrosis by suppressing TLR4 and NLRP3 signaling pathways.
Biomed Pharmacother
; 177: 116952, 2024 Aug.
Article
in En
| MEDLINE
| ID: mdl-38917754
ABSTRACT
BACKGROUND:
Non-alcoholic steatohepatitis (NASH) and liver fibrosis are progressive conditions associated with non-alcoholic fatty liver disease (NAFLD), characterized by hepatocyte pyroptosis and hepatic stellate cell (HSC) activation. Gentiopicroside (GPS) has emerged as a potential treatment for NASH, yet its underlying mechanism remains unclear.AIM:
To confirm that GPS can improve NASH and liver fibrosis by blocking the NLRP3 signaling pathway STUDYDESIGN:
Initially, different animal models were used to study the effects and mechanisms of GPS on NASH and fibrosis. Subsequent in vitro experiments utilized co-cultures and other techniques to delve deeper into its mechanism, followed by validation of the findings in mouse liver tissues.METHODS:
C57BL/6 mice were fed high-fat, high-cholesterol (HFHC), or methionine-choline-deficient (MCD) diets to induce NASH and fibrosis. RAW264.7 cells and born marrow bone marrow-derived macrophages (BMDMs) were stimulated with LPS and ATP to induce inflammation, then co-cultured with primary hepatocytes and HSCs, treated with GPS, and its efficacy and mechanism were analyzed.RESULTS:
In vivo, GPS alleviated NASH and liver fibrosis by inhibiting the NLRP3 pathway. In vitro, GPS attenuated inflammation induced by BMDMs by inhibiting TLR4 and NLRP3 signaling pathways, and Co-culture studies suggested that GPS reduced hepatocyte pyroptosis and HSC activation, which was also confirmed in liver tissuesCONCLUSION:
GPS improves NASH and liver fibrosis by inhibiting the TLR4 and NLRP3 signaling pathways. The specific mechanism may be related to the suppression of macrophage-mediated inflammatory responses, thereby reducing hepatocyte pyroptosis and HSC activation.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
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Iridoid Glucosides
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Non-alcoholic Fatty Liver Disease
/
Liver Cirrhosis
Limits:
Animals
Language:
En
Journal:
Biomed Pharmacother
/
Biomed. pharmacother
/
Biomedicine & pharmacotherapy
Year:
2024
Type:
Article
Affiliation country:
China