Basic Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 7, 2019; 25(41): 6205-6221
Published online Nov 7, 2019. doi: 10.3748/wjg.v25.i41.6205
Yinchenhao decoction attenuates obstructive jaundice-induced liver injury and hepatocyte apoptosis by suppressing protein kinase RNA-like endoplasmic reticulum kinase-induced pathway
Yan-Li Wu, Zhong-Lian Li, Xi-Bo Zhang, Hao Liu
Yan-Li Wu, Graduate School of Tianjin Medical University, Tianjin 300070, China
Zhong-Lian Li, Xi-Bo Zhang, Department of Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, Tianjin 300100, China
Hao Liu, Graduate School of Tianjin Medical University, Tianjin 300070, China.
Author contributions: Wu YL and Li ZL designed the research; Wu YL and Liu H performed the research; Wu YL and Zhang XB analyzed the data; Wu YL and Li ZL composed the paper.
Supported by the National Natural Science Foundation of China, No. 81273952.
Institutional animal care and use committee statement: The experimental protocol was approved by the Animal Research Committee of Tianjin Nankai Hospital.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines and prepared the manuscript accordingly.
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/
Corresponding author: Zhong-Lian Li, MD, PhD, Chief Doctor, Doctor, Professor, Surgeon, Department of Hepatobiliary and Pancreatic Surgery, Tianjin Nankai Hospital, No. 6, Changjiang Street, Nankai District, Tianjin 300100, China. nkyylzl@163.com
Telephone: +86-22-27435237 Fax: +86-22-27435237
Received: August 8, 2019
Peer-review started: August 8, 2019
First decision: September 18, 2019
Revised: September 26, 2019
Accepted: October 17, 2019
Article in press: October 17, 2019
Published online: November 7, 2019
ARTICLE HIGHLIGHTS
Research background

Biliary obstruction can cause damage to all organs of the body, especially the liver. Chronic biliary obstruction results in ischaemia and hypoxia of hepatocytes and leads to apoptosis. Apoptosis is very important in regulating the homeostasis of the hepatobiliary system. Endoplasmic reticulum (ER) stress induced apoptosis is a hot research topic worldwide. However, there are few studies on liver injury and hepatocyte apoptosis induced by obstructive jaundice (OJ) through activating the ER stress pathway. Previous studies have confirmed that Yinchenhao decoction (YCHD) can effectively alleviate liver function injury and inhibit liver cell apoptosis, but the main mechanism of YCHD has not been clarified.

Research motivation

To provide scientific evidence for clinical application of YCHD in OJ treatment.

Research objectives

This study aimed to clarify the molecular mechanism of YCHD in alleviating OJ-induced liver injury and hepatocyte apoptosis.

Research methods

In this study, the expression levels of protein kinase RNA-like endoplasmic reticulum-resident protein kinase (PERK), CCAAT/enhancer-binding protein homologous protein (CHOP), growth arrest- and DNA damage-inducible gene 34 (GADD34), B cell lymphoma/leukemia-2 gene (Bcl-2), and Bcl-2 related X protein (Bax) were detected in rats and BRL-3A rat hepatocytes, and the changes of PERK, CHOP, GADD34, Bax, and Bcl-2 were detected after the application of YCHD.

Research results

We found that OJ induced liver injury and hepatocyte apoptosis by activating the PERK-CHOP-GADD34 pathways and upregulating Bax/Bcl-2 ratio, and YCHD attenuated these changes by inhibiting the PERK-CHOP-GADD34 pathways and downregulating Bax/Bcl-2 ratio.

Research conclusions

YCHD can attenuate OJ-induced liver injury and hepatocyte apoptosis by inhibiting the PERK-CHOP-GADD34 pathways and downregulating Bax/Bcl-2 ratio. These findings support the clinical use of YCHD for OJ treatment.

Research perspectives

YCHD is a traditional Chinese medicine (TCM) formula that has thousands of years of history for OJ treatment. The combination of TCM and modern medicine can effectively treat OJ.