Abstract

Thalictrum glandulosissimum (TG) is traditionally used for treating ulcerative colitis (UC). Given the continuously increasing global incidence of UC and the limitations of current therapeutic options, there is an urgent need for safer treatments. However, most existing studies have focused on single component. Studies on the multi-component profile of TG's active alkaloids, particularly systematic pharmacokinetic investigations under pathological conditions, remain insufficient. Without a systematic understanding of which components are absorbed into the bloodstream and how their disposition is altered under UC pathology, the clinical translation of TG is significantly hindered. This research first established a UPLC-Q-TOF-MS/MS method to characterize TG's chemical composition, identifying 58 constituents including 16 prototypes. Integrating network pharmacology and in vitro assays, we predicted berberine, coptisine, cryptopine, and berlambine as core components, with STAT3, EGFR, and SRC as key targets. Molecular docking, qRT-PCR, and Western blot were used for validation. Furthermore, a rapid UPLC-MS/MS method was developed and validated to quantify five major bioactive alkaloids in rat plasma. Pharmacokinetic comparisons between normal and UC model rats revealed that UC significantly shortened Tmax (0.5-1.0 h) and increased the Cmax of berberine, coptisine, and columbamine by 1.19- to 1.67-fold (p < 0.05), suggesting enhanced intestinal absorption under inflammation. This study completes a "prediction-verification-application" workflow, laying a solid foundation for further pharmacokinetic-pharmacodynamic investigations into the therapeutic effects of TG in UC.