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

Molecules. 2016 May 30;21(6):698. 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.

Keywords: Jiaqi Ganxian granule; liver fibrosis; metabolomics pathway; serum; ultra-performance liquid chromatography-time-of-flight mass spectrometry.

MeSH terms

  • Animals
  • Biomarkers
  • Carbon Tetrachloride / adverse effects*
  • Chromatography, Liquid
  • Disease Models, Animal
  • Drugs, Chinese Herbal / pharmacology*
  • Energy Metabolism / drug effects
  • Liver Cirrhosis / chemically induced*
  • Liver Cirrhosis / drug therapy
  • Liver Cirrhosis / metabolism*
  • Liver Cirrhosis / pathology
  • Male
  • Medicine, Chinese Traditional
  • Metabolic Networks and Pathways / drug effects
  • Metabolome*
  • Metabolomics* / methods
  • Rats
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • Biomarkers
  • Drugs, Chinese Herbal
  • Carbon Tetrachloride