Feng Baodong, Su Linqi, Yang Yang, Liu Renyan, Zhang Yu, Xin Lingyi, Wang Li, Yang Zhiming, Wei Xuemei, Chen Qinhua
Key Laboratory of TCM Clinical Pharmacy, Shenzhen Baoan Authentic TCM Therapy Hospital, Shenzhen, China.
School of Pharmaceutical Sciences, Hubei University of Medicine, Shiyan, China.
Front Chem. 2024 Dec 11;12:1518110. doi: 10.3389/fchem.2024.1518110. eCollection 2024.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) influenced by multiple factors. Berberine, an isoquinoline alkaloid derived from the root and bark of Franch., has shown promise in managing UC, but its underlying mechanisms remain unclear.
To elucidate the relationship between berberine, ulcerative colitis (UC), and the organism's metabolome, we established a dextran sulfate sodium (DSS)-induced UC model in rats. Colonic tissue was collected for histopathological examination, while plasma samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with dynamic Multiple Reaction Monitoring (dMRM). This approach, characterized by its short analysis time of 20 min per sample, excellent reproducibility, and straightforward data processing, allowed for the comprehensive detection of a wide array of metabolites, including amino acids, lipids, and organic acids, many of which are implicated in the pathophysiology of UC.
Our results showed that berberine modulated the metabolic disturbances of 33 compounds in the plasma of UC rats, primarily including amino acids, pyrimidines, organic phosphoric acids, fatty acyls, and organonitrogen compounds. These altered metabolites were associated with various pathways, such as amino acid metabolism, glutathione metabolism, nicotinate and nicotinamide metabolism, taurine and hypotaurine metabolism, pyrimidine metabolism, glyoxylate and dicarboxylate metabolism, and the citrate cycle (TCA cycle). Notably, 3-hydroxyproline, homocysteic acid, -threonine, -lysine, carbamoyl phosphate, -phosphoethanolamine, taurine, leucine, and phosphorylcholine exhibited significant differences between the Treatment and Model groups, with levels reverting to those of the Control group ( < 0.001). These findings suggested that these compounds may serve as potential plasma biomarkers for UC.
This study provided valuable insights into the mechanism by which berberine exerted its therapeutic effects on UC through metabolomics. Our results highlighted berberine's potential to modulate key metabolic pathways and restore the levels of several metabolites, suggesting its utility as a therapeutic agent for UC. These findings underscored the importance of metabolomics in understanding the pathophysiology and treatment of UC.
溃疡性结肠炎（UC）是一种受多种因素影响的慢性炎症性肠病（IBD）。小檗碱是一种从黄连的根和树皮中提取的异喹啉生物碱，在治疗UC方面显示出前景，但其潜在机制仍不清楚。
为了阐明小檗碱、溃疡性结肠炎（UC）与机体代谢组之间的关系，我们在大鼠中建立了葡聚糖硫酸钠（DSS）诱导的UC模型。收集结肠组织进行组织病理学检查，同时使用液相色谱 - 串联质谱（LC-MS/MS）结合动态多反应监测（dMRM）对血浆样本进行分析。这种方法的特点是每个样本分析时间短，仅20分钟，重现性好，数据处理简单，能够全面检测多种代谢物，包括氨基酸、脂质和有机酸，其中许多与UC的病理生理学有关。
我们的结果表明，小檗碱调节了UC大鼠血浆中33种化合物的代谢紊乱，主要包括氨基酸、嘧啶、有机磷酸、脂肪酰基和有机氮化合物。这些改变的代谢物与各种途径相关，如氨基酸代谢、谷胱甘肽代谢、烟酸和烟酰胺代谢、牛磺酸和亚牛磺酸代谢、嘧啶代谢、乙醛酸和二羧酸代谢以及柠檬酸循环（TCA循环）。值得注意的是，3-羟基脯氨酸、高半胱氨酸、苏氨酸、赖氨酸、氨基甲酰磷酸、磷酸乙醇胺、牛磺酸、亮氨酸和磷酸胆碱在治疗组和模型组之间表现出显著差异，其水平恢复到对照组水平（<0.001）。这些发现表明这些化合物可能作为UC潜在的血浆生物标志物。
本研究通过代谢组学为小檗碱对UC发挥治疗作用的机制提供了有价值的见解。我们的结果突出了小檗碱调节关键代谢途径和恢复几种代谢物水平的潜力，表明其作为UC治疗剂的效用。这些发现强调了代谢组学在理解UC病理生理学和治疗中的重要性。
