Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 7, 2015; 21(17): 5271-5280
Published online May 7, 2015. doi: 10.3748/wjg.v21.i17.5271
Glycyrrhizic acid inhibits apoptosis and fibrosis in carbon-tetrachloride-induced rat liver injury
Bo Liang, Xiao-Ling Guo, Jing Jin, Yong-Chun Ma, Zheng-Quan Feng
Bo Liang, Zheng-Quan Feng, Department of Oncology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
Xiao-Ling Guo, Yong-Chun Ma, Department II of Psychosomatics, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang Province, China
Jing Jin, Department of Ophthalmology, First People’s Hospital of Shanghai Jiaotong University, Shanghai 200080, China
Author contributions: Liang B and Guo XL contributed equally to this work; Liang B and Guo XL performed the majority of experiments and wrote the manuscript; Jin J revised the manuscript and offered vital analytical tools; Ma YC and Feng ZQ designed the study and provided financial support for this work.
Supported by Medical and Health Science and Technology Planning Project of Zhejiang Province in 2012, China, Grant No.2012RCB007.
Ethics approval: The study was reviewed and approved by (Zhongshan Hospital, Fudan University) Institutional Review Board.
Institutional animal care and use committee: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the (Zhongshan Hospital, Fudan University) (IACUC protocol number: SYXK2008-0039).
Data sharing: 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: Yong-Chun Ma, MD, Department II of Psychosomatics, Tongde Hospital of Zhejiang Province, No. 234 Gucui Road, Hangzhou 310012, Zhejiang Province, China. tdxsk2015@163.com
Telephone: +86-571-89972114 Fax: +86-571-88853199
Received: October 29, 2014
Peer-review started: October 29, 2014
First decision: December 26, 2014
Revised: January 27, 2015
Accepted: February 11, 2015
Article in press: February 11, 2015
Published online: May 7, 2015
Processing time: 196 Days and 3.7 Hours
Abstract

AIM: To investigate anti-apoptotic effects of glycyrrhizic acid (GA) against fibrosis in carbon tetrachloride (CCl4)-induced liver injury and its contributing factors.

METHODS: Liver fibrosis was induced by administration of CCl4 for 8 wk. Pathological changes in the liver of rats were examined by hematoxylin-eosin staining. Collagen fibers were detected by Sirius red staining. Hepatocyte apoptosis was determined by TUNEL assay and the expression levels of cleaved caspase-3, Bax, α-SMA, connective tissue growth factor (CTGF), matrix metalloproteinase (MMP) 2 and MMP9 proteins were evaluated by western blot analysis, and α-SMA mRNA, collagen type I and III mRNA were estimated by real-time PCR.

RESULTS: Treatment with GA significantly improved the pathological changes in the liver and markedly decreased the positive area of Sirius red compared with rats in the CCl4-treated group. TUNEL assay showed that GA significantly reduced the number of TUNEL-positive cells compared with the CCl4-treated group. The expression levels of cleaved caspase-3, Bax, α-SMA, CTGF, MMP2 and MMP9 proteins, and α-SMA mRNA, collagen type I and III mRNA were also significantly reduced by GA compared with the CCl4-treated group (P < 0.05).

CONCLUSION: GA treatment can ameliorate CCl4-induced liver fibrosis by inhibiting hepatocyte apoptosis and hepatic stellate cell activation.

Keywords: Glycyrrhizic acid; Hepatocyte apoptosis; Liver fibrosis; Hepatic stellate cell; Matrix metalloproteinase

Core tip: This study showed that glycyrrhizic acid (GA) had inhibitory effects on hepatocyte apoptosis and liver fibrosis, which were mainly associated with down-regulation of hepatic stellate cell (HSC) activation, thus regulating fibrotic-related factors, such as expression levels of connective tissue growth factor, MMP2 and MMP9 proteins, and collagen type I and III mRNA. Collectively, these results demonstrate that GA treatment significantly ameliorated CCl4-induced liver fibrosis by inhibiting hepatocyte apoptosis and HSC activation, which may provide potential therapeutic strategies for anti-fibrosis.