Nontargeted urine metabolomics analysis of the protective and therapeutic effects of Citri Reticulatae Chachiensis Pericarpium on high-fat feed-induced hyperlipidemia in rats

Biomed Chromatogr. 2020 Apr;34(4):e4795. doi: 10.1002/bmc.4795. Epub 2020 Feb 12.


In this study, we focused on studying the changes in urine metabolites in hyperlipidemic rats using ultra-performance liquid chromatography coupled with quadrupole time-of-fight mass spectrometry (UPLC-Q-TOF/MS) and metabolomics, as well as the effect of Citri Reticulatae Chachiensis Pericarpium (CRCP) on hyperlipidemia. These urine samples were examined by UPLC-Q-TOF/MS to obtain MS data. The MS data were analyzed by principal component analysis and partial least squares-discriminant analysis to identify the differential metabolites. CRCP reduced the body weight and levels of triglycerides, total cholesterol and low-density lipoprotein cholesterol and abnormally decreased high-density lipoprotein cholesterol in hyperlipidemic rats, which were significantly raised by a high-fat diet. Twenty-seven potential biomarkers were identified within the complex sample matrix of urine. Fourteen biomarkers increased in the hyperlipidemia rats compared with normal rats. Meanwhile, 13 biomarkers decreased. CRCP reversed abnormal changes in biomarkers, including 5-l-glutamyl-taurine, 5-aminopentanoic acid, cis-4-octenedioic acid and 2-octenedioic acid. These biomarkers show that hyperlipidemia is related to the metabolic pathways of taurine and hypotaurine metabolism, fatty acid biosynthesis, and arginine and proline metabolism. CRCP mainly prevents hyperlipidemia by intervening in these metabolic pathways.

Keywords: Citri Reticulatae Chachiensis Pericarpium; UPLC-Q-TOF/MS; hyperlipidemia; metabolomics; urine.

MeSH terms

  • Animals
  • Biomarkers / urine
  • Citrus / chemistry*
  • Diet, High-Fat*
  • Fruit / chemistry
  • Male
  • Metabolome / drug effects*
  • Metabolomics
  • Plant Preparations* / chemistry
  • Plant Preparations* / pharmacology
  • Protective Agents* / chemistry
  • Protective Agents* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results


  • Biomarkers
  • Plant Preparations
  • Protective Agents