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

Author:

Chen Chin-Chuan12,Chen Chi-Yuan13,Yeh Chau-Ting4,Liu Yi-Tsen1,Leu Yann-Lii12ORCID,Chuang Wen-Yu56,Shih Yin-Hwa7ORCID,Chou Li-Fang8,Shieh Tzong-Ming9ORCID,Wang Tong-Hong1234ORCID

Affiliation:

1. Biobank, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan

2. Graduate Institute of Natural Products, Chang Gung University, Tao-Yuan 33303, Taiwan

3. Graduate Institute of Health Industry and Technology, Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, Chang Gung University of Science and Technology, Tao-Yuan 33303, Taiwan

4. Liver Research Center, Department of Hepato-Gastroenterology, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan

5. Department of Anatomic Pathology, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan

6. College of Medicine, Chang Gung University, Tao-Yuan 33303, Taiwan

7. Department of Healthcare Administration, Asia University, Taichung 41354, Taiwan

8. Kidney Research Center, Chang Gung Memorial Hospital, Tao-Yuan 33305, Taiwan

9. School of Dentistry, China Medical University, Taichung 40402, 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.

Funder

National Science and Technology Council

the Chang Gung Medical Research Program

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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