Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Mar 7, 2018; 24(9): 992-1003
Published online Mar 7, 2018. doi: 10.3748/wjg.v24.i9.992
Autophagy activation by Jiang Zhi Granule protects against metabolic stress-induced hepatocyte injury
Yi-Yuan Zheng, Miao Wang, Xiang-Bing Shu, Pei-Yong Zheng, Guang Ji
Yi-Yuan Zheng, Miao Wang, Xiang-Bing Shu, Pei-Yong Zheng, Guang Ji, Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Author contributions: Zheng YY and Wang M contributed equally as co-first authors; Zheng YY and Wang M performed the majority of experiments and drafted the article; Shu XB established the animal model; Zheng PY analyzed the data; Ji G designed the research; all authors approved the final version of the article to be published.
Supported by the National Natural Science Foundation of China, No. 81370092.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Institute of Digestive Disease, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Shanghai University of Traditional Chinese Medicine (IACUC protocol number Approval number: SZY201508004).
Conflict-of-interest statement: All authors declare that they have no conflicts of interest.
Data sharing statement: No additional data are available.
Open-Access: 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/
Correspondence to: Guang Ji, PhD, Chief Doctor, Professor, Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No. 725 South Wanping Road, Shanghai 200032, China. jiliver@vip.sina.com
Telephone: +86-21-64385700 Fax: +86-21-64385700
Received: November 9, 2017
Peer-review started: November 10, 2017
First decision: December 13, 2017
Revised: December 22, 2017
Accepted: January 1, 2018
Article in press: January 1, 2018
Published online: March 7, 2018
Processing time: 116 Days and 1.2 Hours
ARTICLE HIGHLIGHTS
Research background

Non-alcoholic fatty liver disease (NAFLD), as the leading cause of chronic liver disease, can result in serious liver-related complications and an increase in overall mortality. However, the pathogenesis of NAFLD is still unknown and no effective therapeutic strategy has been accepted as the standard treatment option. In previous studies, the authors found that JZG had beneficial effects in improving hepatic fat accumulation, metabolic disorder and associated liver injury, and its efficacy in patients with NAFLD was also confirmed.

Research motivation

Autophagy is important in liver diseases, and research has demonstrated that autophagy regulators can improve hepatic function. However, no effective therapeutic strategy has been accepted as the standard option for NAFLD and its complications. Thus, novel treatments are still urgently needed to prevent or delay the onset as well as the progression of NAFLD.

Research objectives

NAFLD, as the leading cause of chronic liver disease, could result in serious liver-related complications and an increase in overall mortality. And traditional Chinese medicine, as an alternative and complementary medicine, may be an effective addition to the current standardized intervention strategy.

Research methods

The process of autophagy was detected by the expressions of LC3 and SQSTM1/p62. The upstream event of autophagy induction was presented by LC3-II/actin expression and the downstream event of autophagic flux was presented by the expressions of LC3-II/LC3-I and SQSTM1/p62. Stable fluorescence-expressing cell lines were established with mRFP-GFP-LC3 and mCherry-p62 lentivirus to visualize the whole progression of autophagic flux.

Research results

In previous research, the authors had demonstrated that the Chinese herbal formula JZG had beneficial effects in improving hepatic fat accumulation. In this study, autophagy was demonstrated to be critically involved in this process.

Research conclusions

The authors confirmed that metabolic stress-induced hepatocyte injury exhibited dual effects on autophagy, while JZG activated the whole process to provide beneficial effects in NAFLD.

Research perspectives

The exact compounds contained in this prescription are still unknown and the complex compounds might have led to multitarget effects. A systems pharmacology approach to determine the active compounds and action mechanisms might be a good method for the future research.