Apigenin protects mice against 3,5-diethoxycarbonyl-1,4-dihydrocollidine-induced cholestasis

• Published in: Food & function 2021-03, Vol.12 (5), p.2323-2334
• Main Authors: Zheng, Shihong, Cao, Peichang, Yin, Zequn, Wang, Xuerui, Chen, Yuanli, Yu, Maoyun, Xu, Baocai, Liao, Chenzhong, Duan, Yajun, Zhang, Shuang, Han, Jihong, Yang, Xiaoxiao
• Format: Article
• Language: English
• Subjects: Actin; Antioxidants; Atrophy; Bile; Bile ducts; Biotechnology; Catalase; Cholestasis; Cirrhosis; Collagen; Collagen (type I); Fibrosis; Gallbladder; Gallbladder diseases; Glutathione; Glutathione peroxidase; Growth factors; Hydrogen peroxide; Inflammation; Liver; Liver cirrhosis; Metabolism; Muscles; Oxidants; Oxidative stress; Oxidizing agents; Peroxidase; Receptors; Signal transduction; Smooth muscle; TLR4 protein; Toll-like receptors; Transforming growth factor-b; Tumor necrosis factor-α
• ISSN: 2042-6496; 2042-650X
• DOI: 10.1039/d0fo02910f

Cholestasis can induce liver fibrosis and cirrhosis. Apigenin has anti-oxidant and anti-inflammatory effects. Herein, we determined whether apigenin can protect mice against cholestasis. In vitro , apigenin protected TFK-1 cells (a human bile duct cancer cell line) against H 2 O 2 -induced ROS generation and inhibited transforming growth factor-β-activated collagen type 1 alpha 1 and α-smooth muscle actin in LX2 cells (a human hepatic stellate cell line). In vivo , cholestatic mice induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) were treated with apigenin. Apigenin potently blocked DDC-induced gallbladder atrophy and associated liver injury, fibrosis and collagen accumulation. Moreover, apigenin relieved the DDC-caused abnormality of bile acid metabolism and restored the balance between bile secretion and excretion by regulating the farnesoid X receptor signaling pathway. Furthermore, apigenin reduced inflammation or oxidative stress in the liver by blocking the DDC-activated Toll-like receptor 4, nuclear factor κB and tumor necrosis factor α, or DDC-suppressed superoxidase dismutase 1/2, catalase and glutathione peroxidase. Taken together, apigenin improves DDC-induced cholestasis by reducing inflammation and oxidative damage and improving bile acid metabolism, indicating its potential application for cholestasis treatment. Apigenin prevented the DDC-induced abnormal lipid metabolism, liver damage and liver fibrosis by reducing inflammation and oxidative stress. Apigenin might be a potential drug for the treatment of cholestatic liver diseases.