Cheng QC, Fan J, Deng XW, Liu HC, Ding HR, Fang X, Wang JW, Chen CH, Zhang WG. Dihydromyricetin ameliorates chronic liver injury by reducing pyroptosis. World J Gastroenterol 2020; 26(41): 6346-6360 [PMID: 33244197 DOI: 10.3748/wjg.v26.i41.6346]
Corresponding Author of This Article
Wei-Guang Zhang, MD, PhD, Professor, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China. zhangwg@bjmu.edu.cn
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Quan-Cheng Cheng, Xin-Wei Deng, Huai-Cun Liu, Hui-Ru Ding, Xuan Fang, Jian-Wei Wang, Chun-Hua Chen, Wei-Guang Zhang, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China
Jing Fan, Xin Hua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 202155, China
Author contributions: Cheng QC and Fan J performed the majority of experiments and analyzed the data; Fang X and Chen CH typeset the figures; Deng XW, Liu HC, Wang JW and Ding HR participated equally in treatment of the animals; Zhang WG designed and coordinated the research; Cheng QC wrote the paper.
Supported byNational Natural Science Foundation of China, No. 81873769; and Beijing Municipal Natural Science Foundation, No. 7162098.
Institutional review board statement: The study was reviewed and approved by the Biomedical Ethics Committee of Peking University Institutional Review Board, No. LA2017100.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Peking University, No. SCXK 2016-0010.
Conflict-of-interest statement: There is no conflict of interest in this study.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Wei-Guang Zhang, MD, PhD, Professor, Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, No. 38 Xueyuan Road, Haidian District, Beijing 100191, China. zhangwg@bjmu.edu.cn
Received: May 19, 2020 Peer-review started: May 19, 2020 First decision: July 29, 2020 Revised: July 30, 2020 Accepted: August 29, 2020 Article in press: August 29, 2020 Published online: November 7, 2020 Processing time: 170 Days and 20.8 Hours
ARTICLE HIGHLIGHTS
Research background
Chronic liver injury (CLI) is the beginning of many serious liver diseases. If not timely managed CLI can seriously threaten human health. It has been reported that pyroptosis occurs in CLI. However, there is no drug that reduces CLI by regulating pyroptosis.
Research motivation
To explore the therapeutic effect and mechanism of dihydromyricetin (DHM) on CLI from a new perspective of the pathogenesis of CLI-pyroptosis.
Research objectives
We mainly focused on the regulatory effect of DHM on pyroptosis in CLI. The effect of DHM on pyroptosis was evaluated at the following three levels: Morphology, protein and mRNA. The related mechanism of DHM treatment for CLI was also studied.
Research methods
A CLI mouse model was established by subcutaneous injection of carbon tetrachloride (CCl4) into the back. After establishment of the model, the therapeutic effect of DHM on CLI was estimated by serological detection, HE staining and ORO staining. Western blotting, immunohistochemistry and qRT-PCR were used to detect the changes in pyroptosis-related molecules.
Research results
DHM improved liver damage caused by CCl4, reduced steatosis in hepatocytes, and inhibited the pyroptosis signal.
Research conclusions
DHM can improve CCl4-induced CLI and regulate the pyroptosis pathway in hepatocytes. DHM may be a potential therapeutic drug for CLI.
Research perspectives
As a newly discovered programmed cell death, pyroptosis provides a new direction for the study of the pathogenesis of CLI. DHM affects the mechanism of action by regulating pyroptosis to alleviate CLI. This could be a major breakthrough in the development of drugs for CLI.
