Abstract

Nonalcoholic steatohepatitis (NASH) is the most severe and progressive form of nonalcoholic fatty liver disease (NAFLD), which can lead to life-threatening conditions, however, there is still no approved drug for the treatment of NASH. In this study we used human-like NASH mouse model and treated orally with isorhamnetin at a dose of 50 mg/kg to analyze the effect of isorhamnetin on the progression of NASH. NASH-induced mice represented severe steatosis with inflammation, and fibrosis in liver accompanied with high level of liver injury markers in serum. Isorhamnetin treatment reduced intrahepatic lipid accumulation and TG content by inhibiting de novo lipogenic pathway in NASH-induced mice. Consistent with this, isorhamnetin-treated NASH mice showed improved liver injury markers, reduced collagen deposition as well as decreased gene expression of fibrogenic markers. Taken together, here we showed for the first time that synthesized isorhamnetin alleviates pathologic features of NASH and thus can potentially contribute to NASH drug development.

Details

Title
Isorhamnetin Alleviates Steatosis and Fibrosis in Mice with Nonalcoholic Steatohepatitis
Author
Ganbold, Munkhzul 1 ; Owada, Yohei 2 ; Ozawa, Yusuke 2 ; Shimamoto, Yasuhiro 3 ; Ferdousi, Farhana 4 ; Tominaga, Kenichi 3 ; Yun-Wen, Zheng 2   VIAFID ORCID Logo  ; Ohkohchi, Nobuhiro 2 ; Isoda, Hiroko 5 

1  School of Integrative and Global Majors (SIGMA), University of Tsukuba, Tsukuba, Ibaraki, Japan 
2  Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan 
3  Interdisciplinary Research Center for Catalytic Chemistry, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan 
4  Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki, Japan 
5  School of Integrative and Global Majors (SIGMA), University of Tsukuba, Tsukuba, Ibaraki, Japan; Interdisciplinary Research Center for Catalytic Chemistry, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan; Alliance for Research on the Mediterranean and North Africa (ARENA), University of Tsukuba, Tsukuba, Ibaraki, Japan; Faculty of Life and Environment Science, University of Tsukuba, Tsukuba, Japan 
Pages
1-11
Publication year
2019
Publication date
Nov 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-52736-y
ProQuest document ID
2312795545
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.