Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Pharmacol. Jun 9, 2015; 4(2): 227-235
Published online Jun 9, 2015. doi: 10.5497/wjp.v4.i2.227
Protective effect of fu-qi granule on carbon tetrachloride-induced liver fibrosis in rats
Lin Zhong, Yan-Ling Sun, Wen-Li Shi, Xiao Ma, Zhe Chen, Jia-Bo Wang, Rui-Sheng Li, Xue-Ai Song, Hong-Hong Liu, Yan-Ling Zhao, Xiao-He Xiao
Lin Zhong, Xiao Ma, Zhe Chen, Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan Province, China
Yan-Ling Sun, Division I, Second Hepatobiliary Surgery Center, 302 Military Hospital of China, Beijing 100039, China
Wen-Li Shi, Xue-Ai Song, Hong-Hong Liu, Department of Integrative Medical Center, 302 Military Hospital of China, Beijing 100039, China
Jia-Bo Wang, Yan-Ling Zhao, Xiao-He Xiao, China Military Institute of Chinese Medicine, 302 Military Hospital of China, Beijing 100039, China
Rui-Sheng Li, Research and Technology Service Center, 302 Military Hospital of China, Beijing 100039, China
Author contributions: In the study, Zhao YL and Xiao XH paraticipated in research design and professional guidance; Zhong L, Ma X and Chen Z perfomed the majority of experiments, and also involved in editing the manuscript entitled; Sun YL, Shi WL, Li RS, Song XA and Liu HH provided vital reagents and analytical tools; Wang JB interpreted the data and revised the manuscript; all authors read and approved the final version of the manuscript.
Supported by The National Natural Sciences Foundation, No. 81173571; National Basic Research Program of China, No. 2007CB512607; The Major Projects of the National Science and Technology, No. 2012ZX10005010-002-002.
Ethics approval: The study entitle “Protective Effect of Fu-qi Granule on CCl4-induced Liver Fibrosis in Rat” was reviewed and approved by the Institutional Review Board of China Military Institute of Chinese Medicine, 302 Military Hospital of China. This study has authenticity and reliability.
Institutional animal care and use committee: In the study entitled “Protective Effect of Fu-qi Granule on CCl4-induced Liver Fibrosis in Rat”, all procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Human and Animal Subjects in Teaching and Research (HASC) of the 302 Military Hospital of China. (IACUC protocol number: DWFL-2013-D018). Sixty Sprague-Dawley male rats (180-200 g) were obtained from Experimental Animal Center of Medical Sciences of Chinese People’s Liberation Army of Beijing, China. Animal certificate was SCXK-(Army) 2012-0004.
Conflict-of-interest: The authors declared that they have no competing interests.
Data sharing: Technical appendix, statistical code, and dataset are stored and available at China Military Institute of Chinese Medicine, 302 Military Hospital of China. E-mail: zhaoyl2855@126.com. Participants gave informed consent for data sharing.
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: Yan-Ling Zhao, Professor, China Military Institute of Chinese Medicine, 302 Military Hospital of China, 100#, the 4th Ring Road, Beijing 100039, China. zhaoyl2855@126.com
Telephone: +86-10-66933320 Fax: +86-10-66933320
Received: October 12, 2014
Peer-review started: October 13, 2014
First decision: December 26, 2014
Revised: January 9, 2015
Accepted: April 8, 2015
Article in press: April 9, 2015
Published online: June 9, 2015
Processing time: 250 Days and 4.6 Hours
Abstract

AIM: To investigate the efficacy of fu-qi granule (FQG) on carbon tetrachloride (CCl4) induced liver fibrosis in rats and the underlying mechanisms.

METHODS: Sixty rats were randomly divided into six groups: normal control group, CCl4 induced liver fibrosis group, AnluoHuaxianWan group and three treatment groups of FQG. Treatment of rats with intraperitoneal injection of carbon tetrachloride solution at 0.3 mL per 100 g body weigh twice a week for 8 wk. The normal control group the rats were given the media (olive oil) at the same time. In the first 2 wk, rats were raised with feedstuff (80% corn meal, 20% lard, 0.5% cholesterol). Serum samples were collected for alanine transaminase, aspartate aminotransferase, alkaline phosphatase, albumin, total protein assay and typical histopathological changes was observed in Hematoxylin-eosin staining sections. Smooth muscle alpha actin (α-SMA) was analyzed with immunohistochemistry. Mammalian target of rapamycin (mTOR) and hypoxia-inducible factor-1 (HIF-1α) expressions were detected by Western blotting. Tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) and matrix metalloproteinases-9 (MMP-9) were measured with semi-quantitative reverse transcriptase-polymerase chain reaction.

RESULTS: FQG significantly reduced the serum levels of alanine transaminase, aspartate aminotransferase, alkaline phosphatase and increased the serum contents of albumin, total protein in rats with liver fibrosis. Moreover, FQG promoted extracellular matrix degradation by increasing MMP-9 and inhibiting TIMP-1 and α-SMA. mTOR and HIF-1α expression in liver significantly decreased in the rats treated with FQG.

CONCLUSION: The results indicated that FQG significantly reverse fibrosis induced by CCl4, which should be developed as a new and promising preparation for the prevention of liver fibrosis.

Keywords: Protective effect; Fu-qi granule; Carbon tetrachloride; Mammalian target of rapamycin/p70S6K signal pathway; Liver fibrosis

Core tip: Fu-qi granule (FQG) is traditional Chinese medicine preparation to prove the antifibrotic properties of traditional Chinese drug composed of six medicinal herbs in rats treated with carbon tetrachloride. we checked activities of liver enzymes, histopathological changes within the liver as well as the expression of mammalian target of rapamycin (mTOR) and hypoxia-inducible factor-1 and tissue inhibitor of matrix metalloproteinases-1 and matrix metalloproteinases-9. FQG can attenuate liver fibrosis induced by carbon tetrachloride via mTOR/p70S6K signal transduction pathway.