Evaluation of the effect of Dahuang-Mudan decoction on TNBS-induced colitis using UPLC-QTOF/MS-based metabolomic analysis.

ABSTRACT

Dahuang-Mudan decoction (DMD) is a formula that has been widely used as a complementary treatment for inflammatory bowel disease (IBD). However, the mechanism of action of DMD in IBD has not been clearly elucidated. Therefore, we developed a metabolomics-based method to evaluate the effects and potential mechanisms of DMD in a 2,4,6-trinitobenzene sulfonic acid (TNBS)-induced colitis model. The ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/QTOF-MS) method combined with multiple analysis approaches including principal component analysis, partial least square discriminant analysis and orthogonal partial least square discriminant analysis were used to investigate the different urinary metabolites. We identified 29 potential biomarkers of TNBS-induced colitis that returned to normal conditions after DMD administration. Pathway analysis indicated that changes in these metabolites were associated with cysteine and methionine metabolism, citric acid cycle, glycolysis and glycolic regeneration, pyruvate metabolism, biosynthesis of valine, leucine and isoleucine, biosynthesis of primary bile acids, glycine, serine and threonine metabolism, caffeine metabolism, arginine and proline metabolism and phenylalanine metabolism. It is worth noting that DMD has potential therapeutic effects on TNBS-induced colitis, which functions by restoring the balance of multiple disturbed pathways to a normal condition. This study suggests the reliability of metabolomics-based approaches to identifying biomarkers and pathways, which facilitate further investigation of the potential mechanisms of DMD.