Isoliquiritigenin alleviates the development of alcoholic liver fibrosis by inhibiting ANXA2.
Biomed Pharmacother
; 159: 114173, 2023 Mar.
Article
en En
| MEDLINE
| ID: mdl-36680814
ABSTRACT
The study aimed to investigate the effect of isoliquiritigenin (ISL) on model of alcoholic liver fibrosis (ALF). C57BL/6 mice were used to establish animal model of ALF, HSC-T6 cells were used to establish alcohol-activated cell model, and tandem mass tag (TMT) assays were used to analyze the proteome. The results showed that ISL obviously alleviated hepatic fibrosis in model mice. ISL visually improved the area of liver pathological stasis and deposition of fibrillar collagen (Sirius Red staining, Masson staining), inhibited the mRNA expression levels of interleukin 6 (IL-6), tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) in liver tissues. ISL down-regulated the mRNA expression levels of IL-6 and transforming growth factor-ß1(TGF-ß1) in activated hepatic stellate cells (HSCs). And ISL significantly reduced annexin A2 (ANXA2) in vitro detected by TMT proteomics technology. Interestingly, it was found for the first time that ISL could inhibit ANXA2 expression both in vivo and in vitro, block the sphingosine kinases (SPHKs)/sphingosine-1-phosphate (S1P)/interleukin 17 (IL-17) signaling pathway and regulate the expression of α-smooth muscle actin (α-SMA) by inhibiting the phosphorylation of signal transducer and activator of transcription 3 (STAT3) at the downstream signal to finally reverse HSCs activation and hepatic fibrosis. Thus, we demonstrated that ISL is a drug monomer with notable anti-hepatic fibrosis activity.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Interleucina-6
/
Anexina A2
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Biomed Pharmacother
Año:
2023
Tipo del documento:
Article
País de afiliación:
China