Corylin Attenuates CCl 4 -Induced Liver Fibrosis in Mice by Regulating the GAS6/AXL Signaling Pathway in Hepatic Stellate Cells

• Published in: International journal of molecular sciences Vol. 24; no. 23
• 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: Journal Article
• Language: English
• Published: Switzerland 29.11.2023
• Subjects: Animals; Anti-Inflammatory Agents - adverse effects; Carbon Tetrachloride; Flavonoids - pharmacology; Flavonoids - therapeutic use; Hepatic Stellate Cells - metabolism; Humans; Liver - metabolism; Liver Cirrhosis - chemically induced; Liver Cirrhosis - drug therapy; Liver Cirrhosis - metabolism; Mice; Phosphatidylinositol 3-Kinases - metabolism; Signal Transduction; liver fibrosis; growth arrest-specific gene 6/AXL signaling pathway; anti-inflammation; hepatic stellate cell; corylin
• ISSN: 1422-0067

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 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.