Corylin Attenuates CCl4-Induced Liver Fibrosis in Mice by Regulating the GAS6/AXL Signaling Pathway in Hepatic Stellate Cells

Liver fibrosis is reversible when treated in its early stages and when liver inflammatory factors are inhibited. Limited studies have investigated the therapeutic effects of corylin, a flavonoid extracted from Psoralea corylifolia L. (Fabaceae), on liver fibrosis. Therefore, we evaluated the anti-in...

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Published in:International journal of molecular sciences 2023-12, Vol.24 (23), p.16936
Main Authors: Chen, Chin-Chuan, Chen, Chi-Yuan, Yeh, Chau-Ting, Liu, Yi-Tsen, Leu, Yann-Lii, Chuang, Wen-Yu, Shih, Yin-Hwa, Chou, Li-Fang, Shieh, Tzong-Ming, Wang, Tong-Hong
Format: Article
Language:English
Subjects:
anti-inflammation
Bacterial infections
Cancer therapies
Collagen
corylin
Cytokines
Flavonoids
growth arrest-specific gene 6/AXL signaling pathway
hepatic stellate cell
Hepatitis
Infections
Inflammation
Kinases
Liver cancer
Liver cirrhosis
liver fibrosis
Natural products
Physiology
Proteins
Tumor necrosis factor-TNF
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Summary:Liver fibrosis is reversible when treated in its early stages and when liver inflammatory factors are inhibited. Limited studies have investigated the therapeutic effects of corylin, a flavonoid extracted from Psoralea corylifolia L. (Fabaceae), on liver fibrosis. Therefore, we evaluated the anti-inflammatory activity of corylin and investigated its efficacy and mechanism of action in ameliorating liver fibrosis. Corylin significantly inhibited inflammatory responses by inhibiting the activation of mitogen-activated protein kinase signaling pathways and the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha in human THP-1 and mouse RAW264.7 macrophages. Furthermore, corylin inhibited the expression of growth arrest-specific gene 6 in human hepatic stellate cells (HSCs) and the activation of the downstream phosphoinositide 3-kinase/protein kinase B pathway. This inhibited the activation of HSCs and the expression of extracellular matrix proteins, including α-smooth muscle actin and type I collagen. Additionally, corylin induced caspase 9 and caspase 3 activation, which promoted apoptosis in HSCs. Moreover, in vivo experiments confirmed the regulatory effects of corylin on these proteins, and corylin alleviated the symptoms of carbon tetrachloride-induced liver fibrosis in mice. These findings revealed that corylin has anti-inflammatory activity and inhibits HSC activation; thus, it presents as a potential adjuvant in the treatment of liver fibrosis.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms242316936