Urine metabolic profile changes of CCl4-liver fibrosis in rats and intervention effects of Yi Guan Jian Decoction using metabonomic approach

Xiaojun Gou,Yongyu Zhang,Qing Tao,Wenyu Wang,Jianye Dai,Yiyang Hu,Qin Feng,Yu Zhao,Jinghua Peng,Ping Liu

doi:10.1186/1472-6882-13-123

Abstract

BackgroundYi Guan Jian Decoction (YGJD), a famous Chinese prescription, has long been employed clinically to treat liver fibrosis. However, as of date, there is no report on the effects of YGJD from a metabonomic approach. In this study, a urine metabonomic method based on gas chromatography coupled with mass spectrometry (GC/MS) was employed to study the protective efficacy and metabolic profile changes caused by YGJD in carbon tetrachloride (CCl4)-induced liver fibrosis.MethodsUrine samples from Wistar rats of three randomly divided groups (control, model, and YGJD treated) were collected at various time-points, and the metabolic profile changes were analyzed by GC/MS with principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA). Furthermore, histopathology and biochemical examination were also carried out to ensure the success of CCl4-induced liver fibrosis model.ResultsUrine metabolic profile studies suggested distinct clustering of the three groups, and YGJD group was much closer to the control group by showing a tendency of recovering towards the control group. Fourteen significantly changed metabolites were found, and YGJD treatment could reverse the levels of these metabolites to normal levels or close to normal levels.ConclusionsThe current study indicates that the YGJD has significant anti-fibrotic effects on CCl4-induced liver fibrosis in rats, which might be by regulating the dysfunction of energy metabolism, amino acid metabolism, tryptophan metabolism, cytochrome P450 metabolism, and gut microflora metabolism. The metabonomic approach can be recommended to study the pharmacological effect and mechanism of complex Chinese medicines.

Highlights

Yi Guan Jian Decoction (YGJD), a famous Chinese prescription, has long been employed clinically to treat liver fibrosis
Urine sample preparation and gas chromatography coupled with mass spectrometry (GC/MS) analysis The urine sample preparation and GC/MS analysis were performed as described by Qiu Y et al [26], which were shown in the Additional file 1
The present study demonstrated that YGJD, a standardized extract of a Traditional Chinese Medicine (TCM) formula, had therapeutic effects on Carbon tetrachloride (CCl4)-induced liver fibrosis in rats

Summary

Introduction

Yi Guan Jian Decoction (YGJD), a famous Chinese prescription, has long been employed clinically to treat liver fibrosis. YGJD suppressed the elevation of serum glutamate oxaloacetate transaminase (GOT) and serum glutamic pyruvic transaminase (GPT) and significantly reduce the accumulation of collagen α1-I, tissue inhibitor of metalloproteinase −1 (TIMP)-1 and alpha-smooth muscle actin (α-SMA) in liver tissues [9] It significantly inhibited carbon tetrachloride (CCl4)-induced liver fibrosis and cirrhosis in rats, which might be associated with decrease in the liver content of hydroxyproline, α-SMA mRNA and Afamin mRNA expression [10,11]. The major active constituents of YGJD, ferulic acid and catalpol, significantly inhibited the progression of CCl4-induced hepatic fibrosis induced in rats [12] These constituents may contribute to understand the protective efficacy and therapeutic mechanism of YGJD

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Discussion

Conclusion