Abstract

Pattern classification is a key approach in Traditional Chinese Medicine (TCM), and it is used to classify the patients for intervention selection accordingly. TCM cold and heat patterns, two main patterns of rheumatoid arthritis (RA) had been explored with systems biology approaches. Different regulations of apoptosis were found to be involved in cold and heat classification in our previous works. For this study, the metabolic profiling of plasma was explored in RA patients with typical TCM cold or heat patterns by integrating liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) platforms in conjunction with the Ingenuity Pathway Analysis (IPA) software. Three main processes of metabolism, including amino acid, carbohydrate and lipid were focused on for function analysis. The results showed that 29 and 19 differential metabolites were found in cold and heat patterns respectively, compared with healthy controls. The perturbation of amino acid metabolism (increased essential amino acids), carbohydrate metabolism (galactose metabolism) and lipid metabolism, were found to be involved in both cold and heat pattern RA. In particular, more metabolic perturbations in protein and collagen breakdown, decreased glycolytic activity and aerobic oxidation, and increased energy utilization associated with RA cold pattern patients. These findings may be useful for obtaining a better understanding of RA pathogenesis and for achieving a better efficacy in RA clinical practice.

Highlights

  • Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that affects different parts of the body, inevitably causing multi-organ disorders

  • The information of Traditional Chinese Medicine (TCM) pattern differentiation based on, such as color of tongue, pulse feelings, which is judged by clinical practitioner with subjective factor in part, and our previous studies showed that more understandable symptoms and related signs can be used for TCM pattern differentiation which judged by modern biological techniques [7,8]

  • Utilizing liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) platforms, we investigated the metabolic changes in plasma of RA patients with cold pattern compared with healthy controls and changes in RA patients with heat pattern compared with healthy controls

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Summary

Introduction

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that affects different parts of the body, inevitably causing multi-organ disorders. According to TCM theory, pattern differentiation is one of the most important concepts in the practice of TCM, and the clinical efficacy would increase if right TCM pattern is chosen during the treatment process [2,3]. It consists of a series of diagnostic information including symptoms, tongue appearance and pulse feelings of patients [4]. Recent evidence has demonstrated that a metabolomics approach can be an effective tool in characterizing the metabolic changes of RA [20,21], maybe in deciphering RA patients with cold and heat TCM patterns in our conjecture. We conducted the analysis of bio-functions and canonical pathways using the Ingenuity Pathway Analysis (IPA) software (Ingenuity, Redwood City, CA, USA) for the differential metabolites to gain insight into the typical metabolic perturbations network associated with the given patterns of RA

Results
Comparison Analysis between Cold and Heat Patterns in Amino Acids Metabolism
Comparison Analysis between Cold and Heat Patterns in Lipid Metabolism
Fatty acid metabolism
Discussion
Chemicals
Patients and Sample Preparation
Data Analysis
Pathway Analysis Using Ingenuity Pathways Analysis Software
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