Background: Damp retention in the middle-jiao syndrome (DRMS), a common manifestation in Traditional Chinese Medicine (TCM), results from stagnation of damp pathogens in the middle jiao and impaired transport of food and fluids. Given the complex pathogenesis of DRMS, this study aimed to investigate its biological mechanisms using an advanced analytical approach. Methods: A DRMS rat model was established based on three etiological factors: dietary disorders, depletion of vital qi, and excessive external dampness. Model validity was assessed via small intestinal carbon propulsion rate and histopathological examination. Urine metabolomics, using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS), systematically characterized metabolic profile changes and potential biomarkers. Results: DRMS rats exhibited significantly reduced small intestinal propulsion, along with varying degrees of edema, disorganized tissue structures, and inflammatory cell infiltration in gastric, renal, and small intestinal tissues. Metabolomic analysis identified 52 differential metabolites as potential DRMS biomarkers, primarily involved in phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine and tyrosine metabolism, the citrate cycle, and cysteine and methionine metabolism pathways. Metabolic correlation networks further validated the model’s accuracy. Discussion: The identified metabolites and pathways provide insight into the mechanisms underlying DRMS, complement existing TCM research, and offer a foundation for further studies. However, the findings are currently limited to the rat model and require human validation. Conclusions: This study successfully established a DRMS animal model under clinically relevant TCM conditions and demonstrated the utility of metabolomics in elucidating DRMS mechanisms, providing experimental evidence for TCM syndrome characterization and advancing understanding of its etiology.
Li et al. (Mon,) studied this question.