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Corylin Attenuates CCl4-Induced Liver Fibrosis in Mice by Regulating the GAS6/AXL Signaling Pathway in Hepatic
Chin-Chuan Chen1,2, Chi-Yuan Chen1,3, Chau-Ting Yeh4
1Biobank, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan.
Abstract:
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.
Insights
Corylin, a flavonoid, demonstrates anti-inflammatory effects and inhibits liver fibrosis by reducing inflammatory factors and hepatic stellate cell activation. This natural compound shows promise as an adjuvant therapy for liver fibrosis.
Area of Science:
- Pharmacology
- Hepatology
- Immunology
Background:
- Liver fibrosis is a reversible condition in early stages, often linked to inflammation.
- Limited research exists on corylin, a flavonoid from Psoralea corylifolia L., for liver fibrosis treatment.
- Investigating natural compounds for liver fibrosis offers potential therapeutic avenues.
Purpose of the Study:
- To evaluate the anti-inflammatory activity of corylin.
- To investigate corylin's efficacy in ameliorating liver fibrosis.
- To elucidate the mechanism of action of corylin in liver fibrosis.
Main Methods:
- Assessed corylin's effect on inflammatory signaling pathways (MAPK) and cytokine expression (IL-1β, IL-6, TNF-α) in macrophages.
- Examined corylin's impact on growth arrest-specific gene 6 (GAS6) and PI3K/Akt pathway in hepatic stellate cells (HSCs).
- Evaluated corylin's role in HSC activation, extracellular matrix (ECM) protein expression, and apoptosis induction (caspase 9/3).
- Confirmed in vivo effects using a carbon tetrachloride-induced liver fibrosis mouse model.
Main Results:
- Corylin significantly inhibited inflammatory responses in macrophages by suppressing MAPK activation and key inflammatory cytokines.
- Corylin reduced GAS6 expression and inhibited the PI3K/Akt pathway in HSCs, thereby reducing HSC activation and ECM production (α-SMA, collagen I).
- Corylin induced apoptosis in HSCs via caspase 9 and caspase 3 activation.
- In vivo studies demonstrated corylin's efficacy in alleviating carbon tetrachloride-induced liver fibrosis symptoms in mice.
Conclusions:
- Corylin exhibits significant anti-inflammatory properties.
- Corylin effectively inhibits hepatic stellate cell activation and promotes their apoptosis.
- Corylin demonstrates therapeutic potential as an adjuvant treatment for liver fibrosis.
