Abstract

Qushi Huayu Decoction (QSHY), clinically derived, consists of five crude drugs, commonly used in treating fatty liver in a clinical setting. However, little is known about its metabolomics study. Herein, the serum and liver tissue metabolomics approach, based on gas chromatography coupled to spectrometry (GC/MS), was employed to evaluate the efficacy and the mechanism underlying QSHY in a rat model of high-fat diet-induced fatty liver. With pattern recognition analysis of serum and liver tissue metabolite profile, a clear separation of model group and control group was acquired for serum and liver tissue samples, respectively. The QSHY group showed a predisposition towards recovery mimicking the control group, which was in agreement with the biochemical alterations and histological results. 23 candidate biomarkers were identified in the serum and liver tissue samples that were utilized for exploring the underlying mechanism. The present study suggests that QSHY has significant anti-fatty liver effects on high-fat diet-induced fatty liver in rats, which might be attributed to regulating the dysfunction of beta-alanine metabolism, alanine, aspartate, and glutamate metabolism, glycine, serine, and threonine metabolism, pyruvate metabolism, and citrate cycle. Thus, metabolomics is a useful tool in the evaluation of the efficacy and elucidation of the mechanism underlying the complex traditional Chinese medicine prescriptions.

Highlights

  • Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction, which represents a wide spectrum of metabolic abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and advanced hepatic fibrosis as well as cirrhosis [1, 2]

  • A metabolomics approach based on gas chromatography coupled to spectrometry (GC/mass spectrometry (MS)) has been developed to establish the metabolomic profiles of serum and liver tissue in rats in order to investigate the anti-fatty liver effect of Qushi Huayu Decoction (QSHY) and its underlying mechanism. 23 endogenous metabolites in the serum and liver tissue samples were considered as potential biomarkers for the separation of the groups

  • Combined with the result of the assay evaluating the physiological parameters and the histology, the changes in the serum and liver metabolites suggested that the disorders of beta-alanine metabolism, alanine, aspartate, and glutamate metabolism, glycine, serine, and threonine metabolism, pyruvate metabolism, and citrate cycle are related to fatty liver induced by high-fat diet and the potential effect of QSHY on some of the above metabolic pathways

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Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver dysfunction, which represents a wide spectrum of metabolic abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and advanced hepatic fibrosis as well as cirrhosis [1, 2]. It is strongly associated with the components of the metabolic syndromes including obesity, insulin resistance, dyslipidemia, and type 2 diabetes mellitus (T2DM) [3]. No specific registered drug is available for the treatment of NAFLD [5]. Traditional Chinese medicine (TCM) has been practiced widely in China for thousands of years and is such a complementary and alternative therapeutic approach

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