Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2016; 22(8): 2558-2565
Published online Feb 28, 2016. doi: 10.3748/wjg.v22.i8.2558
Improved prescription of taohechengqi-tang alleviates D-galactosamine acute liver failure in rats
Yang Zhang, Jian-Xing Luo, Xiao-Yu Hu, Fang Yang, Sen Zhong, Wu Lin
Yang Zhang, Jian-Xing Luo, Xiao-Yu Hu, Sen Zhong, Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
Fang Yang, Department of Neurology, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
Wu Lin, Department of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, Sichuan Province, China
Author contributions: Zhang Y and Luo JX contributed equally to this work; Hu XY and Zhong S designed the study; Hu XY, Zhang Y, Luo JX, Yang F and Lin W performed study; Zhang Y and Yang F analyzed data; and Zhang Y wrote the paper.
Supported by National Key Technology R and D Program, No. 2008ZX10005 and No. 2009ZX10005.
Institutional review board statement: This study was approved by the Institutional Review Board of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Institutional animal care and use committee statement: All animal experiments were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and approved by the Institutional Animal Care and Use Committee of Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Conflict-of-interest statement: The authors declare that there is no conflict of interest related to this study.
Data sharing statement: There are no additional data 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: Dr. Xiao-Yu Hu, Department of Infectious Diseases, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shierqiao Street, Chengdu 610072, Sichuan Province, China. xiaoyuhu@aliyun.com
Telephone: +86-28-87766041 Fax: +86-28-87732407
Received: July 8, 2015
Peer-review started: July 9, 2015
First decision: September 29, 2015
Revised: October 13, 2015
Accepted: November 24, 2015
Article in press: November 24, 2015
Published online: February 28, 2016
Abstract

AIM: To investigate the hepatoprotective effect of improved prescription of Taohechengqi-tang (IPTT) against acute liver failure (ALF) in rats.

METHODS: Seventy specific pathogen free male Wistar rats were randomly divided into four groups: control group (normal rats, n = 10), ALF group (ALF model, n = 20), Stronger Neo-Minophagen C (SNMC) group (ALF model + SNMC, n = 20), and IPTT group (ALF model + IPTT, n = 20). The ALF model group was administered an intraperitoneal injection of D-galactosamine (1.4 g/kg), and the control group received normal saline intraperitoneally. The SNMC and IPTT groups were treated with SMMC (15.6 mg/kg) or IPTT (28.6 g/kg) by gavage at 24 h intervals, and the ALF and control groups were treated with normal saline. At 36 h after injection, serum alanine aminotransferase, aspartate aminotransferase, total bilirubin, albumin, and cholinesterase and prothrombin time were determined, and liver histopathological scores were observed by microscopy after hematoxylin and eosin staining. mRNA expression of high mobility group box (HMGB) 1, toll-like receptor (TLR) 4, nuclear factor kappa B (NF-κB) and caspase-3 were analyzed via fluorescence quantitative reverse transcriptase polymerase chain reaction. Proliferating cell nuclear antigen (PCNA) immunohistochemistry in liver tissue was also performed.

RESULTS: D-galactosamine notably decreased the biochemical and coagulation profiles in serum. IPTT not only improved liver function and histopathology but also normalized the gene expression levels in liver tissue. Compared with the model group, in the IPTT and SNMC groups, HMGB1 mRNA/β-actin (0.06 ± 0.03, 0.11 ± 0.04 vs 0.25 ± 0.04, P < 0.05); TLR4 mRNA/β-actin (0.07 ± 0.02, 0.22 ± 0.08 vs 0.41 ± 0.22, P < 0.05); NF-κB mRNA/β-actin (0.74 ± 0.41, 1.78 ± 0.64 vs 2.68 ± 1.35, P < 0.05); and caspase-3 mRNA/β-actin levels were all significantly reduced (1.61 ± 0.45, 2.57 ± 1.04 vs 3.41 ± 0.85, P < 0.05). The gene expression levels were significantly lower in the IPTT group than in the SNMC group (P < 0.05). Compared with the model group, the PCNA expression in liver tissue was significantly enhanced in the IPTT and SNMC groups (36.34 ± 4.91, 25.57 ± 2.94 vs 17.55 ± 2.40, P < 0.05).

CONCLUSION: IPTT attenuates inflammation in ALF via inhibition of HMGB1 production, which may contribute to limited liver regeneration.

Keywords: Acute liver failure, Traditional Chinese medicine, Taohechengqi-tang, High mobility group box 1, Inflammation

Core tip: Acute liver failure (ALF) is a life-threatening condition. Our prospective cohort study demonstrated that high doses of herbs for clearing heat and resolving stasis have a protective effect on LF. However, the curative mechanism is unclear. Our evidence showed that improved prescription of Taohechengqi-tang attenuated the inflammatory reaction of ALF in rats via inhibition of high mobility group box 1 production, which may contribute to recovery of limited liver regeneration. We provide evidence for the clinical application of Chinese herbs for clearing heat and resolving stasis.