title: Rapid-resolution liquid chromatography TOF-MS for urine metabolomic analysis of collagen-induced arthritis in rats and its applications.
abstract: OBJECTIVE
  Rheumatoid arthritis (RA) is a kind of autoimmune diseases characterized by persistent synovitis, systemic inflammation and autoantibodies. Huang-Lian-Jie-Du-Tang (HLJDT) is a traditional Chinese medicine (TCM) with anti-inflammatory activity. In the present study, a rapid-resolution liquid chromatography tandem time-of-flight mass spectrometry (RRLC-TOF-MS) based metabolomic study was developed to obtain a systematic view of the progression of RA and assess the efficacy of HLJDT and its components in collagen-induced arthritis (CIA) rats.
  
  
  METHODS
  Forty male Wistar rats were randomly divided into five groups, including model group, normal control group, dexamethasone group, HLJDT group and the mixture of 13 components of HLJDT group after immunized with bovine type II collagen. Urine samples for metabolomic study were collected on 8, 15, 22 day during the animal experiment.
  
  
  RESULTS
  The pharmacological changes (swelling paws and arthritis scores) showed that prophylactic treatment with HLJDT and its components significantly suppressed the swelling of rats' paws. By combining with partial least squares discriminant analysis, 24 potential biomarkers were identified and primarily involved in 12 metabolism pathways, such as tricarboxylic acids cycle metabolism, lipid metabolism, tryptophan metabolism and phenylalanine metabolism, which revealed a new insight into the RA network in vivo. These potential metabolites identified in CIA model need to be further investigated to prove their diagnostic and/or prognostic values for RA. Taking potential biomarkers found in the study as screening indexes, it revealed that HLJDT and its components could reverse the pathological process of RA through partly regulating the disturbed metabolic pathways.
  
  
  CONCLUSIONS
  This study indicated that the metabolomic strategy based on RRLC-TOF-MS is a useful tool to search potential biomarkers related to RA and to dissect the underlying mechanisms of TCM in treating RA.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
authors.forename: Rongcai
authors.initials: R
authors.lastname: Yue
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.forename: Yaohua
authors.initials: Y
authors.lastname: Hu
authors.forename: Peng
authors.initials: P
authors.lastname: Jiang
authors.forename: Shuping
authors.initials: S
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Xiang
authors.forename: Wencong
authors.initials: W
authors.lastname: Liu
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.forename: Runhui
authors.initials: R
authors.lastname: Liu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D002853:Chromatography, Liquid / Q000379:methods; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D055432:Metabolomics; D008517:Phytotherapy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D004365:Drugs, Chinese Herbal; C045607:huang-lien-chieh-tu-tang