Baodong Feng ^* Linqi Su ^* Yang Yang ^* Renyan Liu ^* Yu Zhang ^* Lingyi Xin ^* Li Wang ^* Xuemei Wei ^* Qinhua Chen ^*

• Key Laboratory of TCM Clinical Pharmacy, Shenzhen Baoan Authentic TCM Therapy Hospital, Shenzhen,Guangdong, China

Background 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 Coptis chinensis 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 minutes 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, L-threonine, L-lysine, carbamoyl phosphate, O-phosphoethanolamine, taurine, leucine, and phosphorylcholine exhibited significant differences between the Treatment and Model groups, with levels reverting to those of the Control group (p < 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.