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

Abstract
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 H2O2-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.
AuthorsShihong Zheng, Peichang Cao, Zequn Yin, Xuerui Wang, Yuanli Chen, Maoyun Yu, Baocai Xu, Chenzhong Liao, Yajun Duan, Shuang Zhang, Jihong Han, Xiaoxiao Yang
JournalFood & function (Food Funct) Vol. 12 Issue 5 Pg. 2323-2334 (Mar 15 2021) ISSN: 2042-650X [Electronic] England
PMID33620063 (Publication Type: Journal Article)
Chemical References
  • 3,5-diethoxycarbonyl-1,4-dihydrocollidine
  • Bile Acids and Salts
  • Protective Agents
  • Pyridines
  • Apigenin
Topics
  • Animals
  • Apigenin (pharmacology)
  • Bile Acids and Salts (metabolism)
  • Cell Line, Tumor
  • Cholestasis (chemically induced, metabolism)
  • Humans
  • Liver (drug effects)
  • Liver Cirrhosis (metabolism)
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Oxidative Stress (drug effects)
  • Protective Agents (pharmacology)
  • Pyridines (adverse effects)
  • Signal Transduction (drug effects)

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