Abstract

Qushi Huayu Decoction (QHD), an important clinically proved herbal formula, has been reported to be effective in treating fatty liver induced by high-fat diet in rats. However, the mechanism of action has not been clarified at the metabolic level. In this study, a urinary metabolomic method based on gas chromatography-mass spectrometry (GC-MS) coupled with pattern recognition analysis was performed in three groups (control, model, and QHD group), to explore the effect of QHD on fatty liver and its mechanism of action. There was obvious separation between the model group and control group, and the QHD group showed a tendency of recovering to the control group in metabolic profiles. Twelve candidate biomarkers were identified and used to explore the possible mechanism. Then, a pathway analysis was performed using MetaboAnalyst 3.0 to illustrate the pathways of therapeutic action of QHD. QHD reversed the urinary metabolite abnormalities (tryptophan, uridine, and phenylalanine, etc.). Fatty liver might be prevented by QHD through regulating the dysfunctions of phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and tryptophan metabolism. This work demonstrated that metabolomics might be helpful for understanding the mechanism of action of traditional Chinese medicine for future clinical evaluation.

Highlights

  • Nonalcoholic fatty liver disease (NAFLD) refers to the liver parenchymal cytoplasmic steatosis and fat storage as characteristics of the clinical pathological syndrome excluding alcohol and other determinants of liver damage [1]

  • According to the MetPA analysis (Figure 11), phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and tryptophan metabolism were significantly associated with effect of Qushi Huayu Decoction (QHD) on rat model of fatty liver induced by high-fat diet (Figure 11)

  • The present study describes a urine metabolomic evaluation of rat model of fatty liver induced by high-fat diet and the treatment of QHD based on a gas chromatography-mass spectrometry (GC-mass spectrometry (MS)) metabolomics approach combined with univariate and multivariate analyses

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Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) refers to the liver parenchymal cytoplasmic steatosis and fat storage as characteristics of the clinical pathological syndrome excluding alcohol and other determinants of liver damage [1]. With the improvement of living standards and lifestyle changes, the prevalence of diseases such as obesity, insulin resistance (IR), hyperlipidemia, diabetes, and metabolic syndrome contributes to the development of NAFLD. NAFLD has become the most common cause of chronic liver disease and hepatic enzyme abnormality in western developed countries such as Europe and the United States. The incidence of NAFLD is significantly higher than that of hepatitis B, hepatitis C, and alcoholic liver disease, and it has become one of the most common diseases [6, 7]. The prevalence of NAFLD in China and the Asia Pacific region has increased year by year, and the adult incidence in developed areas of China can reach 15% or BioMed Research International even higher [8].

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