Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 7, 2015; 21(13): 3893-3903
Published online Apr 7, 2015. doi: 10.3748/wjg.v21.i13.3893
Caffeic acid phenethyl ester inhibits liver fibrosis in rats
Mei Li, Xiu-Fang Wang, Juan-Juan Shi, Ya-Ping Li, Ning Yang, Song Zhai, Shuang-Suo Dang
Mei Li, Xiu-Fang Wang, Juan-Juan Shi, Ya-Ping Li, Ning Yang, Song Zhai, Shuang-Suo Dang, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi’an Jiaotong University, Xi’an 710004, Shannxi Province, China
Author contributions: Li M and Wang XF contributed equally to this work; Li M, Wang XF and Dang SS designed the research; Li M, Wang XF, Shi JJ, Li YP, Yang N and Zhai S performed the research; Li M, Wang XF and Li YP analyzed the data; and Li M and Wang XF wrote the paper.
Supported by Liver Fibrosis Foundation of Wang Bao-En, China, No. 20100033; and Science and Technology Foundation of Shaanxi Province, China, No. 2010K01-199.
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: Shuang-Suo Dang, PhD, MD, Department of Infectious Diseases, the Second Affiliated Hospital of Medical School of Xi’an Jiaotong University, No. 157 Xi’wu Road, Xi’an 710004, Shaanxi Province, China. dang212@126.com
Telephone: +86-29-87679688 Fax: +86-29-87679688
Received: August 24, 2014
Peer-review started: August 24, 2014
First decision: September 27, 2014
Revised: October 25, 2014
Accepted: December 5, 2014
Article in press: December 8, 2014
Published online: April 7, 2015
Processing time: 226 Days and 6.9 Hours
Abstract

AIM: To investigate the hepatoprotective effects and antioxidant activity of caffeic acid phenethyl ester (CAPE) in rats with liver fibrosis.

METHODS: A total of 75 male Sprague-Dawley rats were randomly assigned to seven experimental groups: a normal group (n = 10), a vehicle group (n = 10), a model group (n = 15), a vitamin E group (n = 10), and three CAPE groups (CAPE 3, 6 and 12 mg/kg, n = 10, respectively). Liver fibrosis was induced in rats by injecting CCl4 subcutaneously, feeding with high fat forage, and administering 30% alcohol orally for 10 wk. Concurrently, CAPE (3, 6 and 12 mg/kg) was intraperitoneally administered daily for 10 wk. After that, serum total bilirubin (TBil), aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured to assess hepatotoxicity. To investigate antioxidant activity of CAPE, malondialdehyde (MDA), glutathione (GSH) levels, catalase (CAT) and superoxide dismutase (SOD) activities in liver tissue were determined. Moreover, the effect of CAPE on α-smooth muscle actin (α-SMA), a characteristic hallmark of activated hepatic stellate cells (HSCs), and NF-E2-related factor 2 (Nrf2), a key transcription factor for antioxidant systems, was investigated by immunohistochemistry.

RESULTS: Compared to the model group, intraperitoneal administration of CAPE decreased TBil, ALT, and AST levels in liver fibrosis rats (P < 0.05), while serum TBil was decreased by CAPE in a dose-dependent manner. In addition, the liver hydroxyproline contents in both the 6 and 12 mg/kg CAPE groups were markedly lower than that in the model group (P < 0.05 and P < 0.001, respectively). CAPE markedly decreased MDA levels and, in turn, increased GSH levels, as well as CAT and SOD activities in liver fibrosis rats compared to the model group (P < 0.05). Moreover, CAPE effectively inhibited α-SMA expression while increasing Nrf2 expression compared to the model group (P < 0.01).

CONCLUSION: The protective effects of CAPE against liver fibrosis may be due to its ability to suppress the activation of HSCs by inhibiting oxidative stress.

Keywords: Caffeic acid phenethyl ester; Liver fibrosis; Oxidative stress; NF-E2-related factor 2; α-smooth muscle actin

Core tip: It has been demonstrated that caffeic acid phenethyl ester (CAPE) has several biological and pharmacological properties. The aim of this study was to evaluate the hepatoprotective effects and antioxidant activity of CAPE in rats with liver fibrosis, as well as the underlying mechanism.