Pi-Wei Institute, Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.
School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, China.
Biomed Chromatogr. 2021 Mar;35(3):e5003. doi: 10.1002/bmc.5003. Epub 2020 Nov 12.
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.
大黄牡丹汤(DMD)是一种被广泛用于治疗炎症性肠病(IBD)的补充疗法的配方。然而,DMD 在 IBD 中的作用机制尚未明确。因此,我们开发了一种基于代谢组学的方法来评估 DMD 在 2,4,6-三硝基苯磺酸(TNBS)诱导的结肠炎模型中的作用和潜在机制。采用超高效液相色谱/四极杆飞行时间质谱(UPLC/QTOF-MS)方法结合主成分分析、偏最小二乘判别分析和正交偏最小二乘判别分析等多种分析方法,研究不同的尿代谢物。我们鉴定出 29 个 TNBS 诱导的结肠炎的潜在生物标志物,这些标志物在 DMD 给药后恢复正常。途径分析表明,这些代谢物的变化与半胱氨酸和蛋氨酸代谢、柠檬酸循环、糖酵解和糖异生、丙酮酸代谢、缬氨酸、亮氨酸和异亮氨酸生物合成、初级胆汁酸生物合成、甘氨酸、丝氨酸和苏氨酸代谢、咖啡因代谢、精氨酸和脯氨酸代谢以及苯丙氨酸代谢有关。值得注意的是,DMD 对 TNBS 诱导的结肠炎具有潜在的治疗作用,其功能是通过恢复多个失调途径的平衡来实现正常状态。本研究表明基于代谢组学的方法识别生物标志物和途径的可靠性,这有助于进一步研究 DMD 的潜在机制。