Metabolic Profile Changes of CCl₄-Liver Fibrosis and Inhibitory Effects of Jiaqi Ganxian Granule.

Zehao Li,Jian Li,Lidan Li,Changyuan Yu,Hao Li,Ge Wang

doi:10.3390/molecules21060698

Abstract

Jiaqi Ganxian Granule (JGG) is a famous traditional Chinese medicine, which has been long used in clinical practice for treating liver fibrosis. However, the mechanism underlying its anti-hepatic fibrosis is still not clear. In this study, an Ultra-Performance Liquid Chromatography-Time-Of-Flight Mass Spectrometry (UPLC-TOF-MS)-based metabolomics strategy was used to profile the metabolic characteristic of serum obtained from a carbon tetrachloride (CCl4)-induced hepatic fibrosis model in Sprague-Dawley (SD) rats with JGG treatment. Through Principal Component Analysis (PCA) and Partial Least Square Discriminant Analysis (PLS-DA), it was shown that metabolic perturbations induced by CCl4 were inhibited after treatment of JGG, for 17 different metabolites related to CCl4. Among these compounds, the change tendency of eight potential drug targets was restored after the intervention with JGG. The current study indicates that JGG has a significant anti-fibrosis effect on CCl4-induced liver fibrosis in rats, which might be by regulating the dysfunction of sphingolipid metabolism, glycerophospholipid metabolism, N-acylethanolamine biosynthesis, fat digestion and absorption, while glycerophospholipid metabolism played vital roles in the inhibitory effects of JGG on hepatic fibrosis according to Metabolic Pathway Analysis (MetPA). Our findings indicated that the metabolomics approach may provide a useful tool for exploring potential biomarkers involved in hepatic fibrosis and elucidate the mechanisms underlying the action of therapies used in traditional Chinese medicine.

Highlights

Hepatic fibrosis, caused by the imbalance of synthesis and degradation of Extracellular Matrix (ECM) [1], represents the wound healing response of the liver to repeated injury and involves a series of cell types and mediators [2]
Our findings indicated that the metabolomics approach may provide a useful tool for exploring potential biomarkers involved in hepatic fibrosis and elucidate the mechanisms underlying the action of therapies used in traditional
The CCl4 -induced hepatic fibrosis model was constructed in SD rats to investigate the anti-fibrosis effects of Jiaqi Ganxian Granule (JGG)

Summary

Introduction

Hepatic fibrosis, caused by the imbalance of synthesis and degradation of Extracellular Matrix (ECM) [1], represents the wound healing response of the liver to repeated injury and involves a series of cell types and mediators [2]. It is a critical state in chronic liver disease, which remains a major medical problem with significant morbidity and mortality and can eventually develop into irreversible cirrhosis or liver cancer [3]. Antimalarials and related drugs (quinidine), sulfonamides (co-trimoxazole), analgesics and local anesthetics (aspirin) can cause hemolysis in patients with

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Conclusion