Eupatilin Ameliorates Hepatic Fibrosis and Hepatic Stellate Cell Activation by Suppressing beta-catenin/PAI-1 Pathway

作者全名："Hu, Jinyuan; Liu, Yuanyuan; Pan, Zheng; Huang, Xuekuan; Wang, Jianwei; Cao, Wenfu; Chen, Zhiwei"

作者地址："[Hu, Jinyuan; Pan, Zheng; Huang, Xuekuan; Wang, Jianwei; Cao, Wenfu; Chen, Zhiwei] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing 400016, Peoples R China; [Liu, Yuanyuan] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Huang, Xuekuan; Wang, Jianwei; Chen, Zhiwei] Chongqing Coll Tradit Chinese Med, Dept Tradit Chinese Med, Chongqing 402760, Peoples R China"

通信作者："Cao, WF; Chen, ZW (通讯作者)，Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing 400016, Peoples R China.; Chen, ZW (通讯作者)，Chongqing Coll Tradit Chinese Med, Dept Tradit Chinese Med, Chongqing 402760, Peoples R China."

来源：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

ESI学科分类：CHEMISTRY

WOS号：WOS:000958396200001

JCR分区：Q2

影响因子：5.6

年份：2023

卷号：24

期号：6

开始页：　

结束页：　

文献类型：Article

关键词：eupatilin; hepatic fibrosis; HSC; EMT; beta-catenin; PAI-1

摘要："The activation of hepatic stellate cells (HSCs) has proved to be pivotal in hepatic fibrosis. Therefore, the suppression of HSC activation is an effective anti-fibrotic strategy. Although studies have indicated that eupatilin, a bioactive flavone found in Artemisia argyi, has anti-fibrotic properties, the effect of eupatilin on hepatic fibrosis is currently unclear. In this study, we used the human hepatic stellate cell line LX-2 and the classical CCl4-induced hepatic fibrosis mouse model for in vitro and vivo experiments. We found that eupatilin significantly repressed the levels of the fibrotic markers COL1 alpha 1 and alpha-SMA, as well as other collagens in LX-2 cells. Meanwhile, eupatilin markedly inhibited LX-2 cell proliferation, as verified by the reduced cell viability and down-regulation of c-Myc, cyclinB1, cyclinD1, and CDK6. Additionally, eupatilin decreased the level of PAI-1 in a dose-dependent manner, and knockdown of PAI-1 using PAI-1-specific shRNA significantly suppressed the levels of COL1 alpha 1, alpha-SMA, and the epithelial-mesenchymal transition (EMT) marker N-cadherin in LX-2 cells. Western blotting indicated that eupatilin reduced the protein level of beta-catenin and its nuclear translocation, while the transcript level of beta-catenin was not affected in LX-2 cells. Furthermore, analysis of histopathological changes in the liver and markers of liver function and fibrosis revealed that hepatic fibrosis in CCl4-treated mice was markedly alleviated by eupatilin. In conclusion, eupatilin ameliorates hepatic fibrosis and hepatic stellate cell activation by suppressing the beta-catenin/PAI-1 pathway."

基金机构："National Natural Science Foundation of China [82004168, 81973567]; Natural Science Foundation Project of Chongqing [cstc2019jcyj-msxmX0180]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202215101]; Program of Chongqing Health Commission [2019ZY3503]; CQMU Program for Youth Innovation in Future Medicine [W0066]; Xinglin program of Chongqing TCM/TCM-integrated Key discipline [2021-ZDXK-yc03]"

基金资助正文："This work was supported by grants from the National Natural Science Foundation of China (Grant No.: 82004168, 81973567), Natural Science Foundation Project of Chongqing (Grant No.: cstc2019jcyj-msxmX0180), Science and Technology Research Program of Chongqing Municipal Education Commission (Grant No.: KJQN202215101), Program of Chongqing Health Commission (Grant No.: 2019ZY3503), CQMU Program for Youth Innovation in Future Medicine (Grant No.: W0066), and Xinglin program of Chongqing TCM/TCM-integrated Key discipline (Grant No.: 2021-ZDXK-yc03)."