A Comparative Research of the Flavonoid Metabolites From Viscum coloratum in Normal and RA Rats by an Integrated Analytical Strategy

Viscum coloratum (Kom.) Nakai has been demonstrated to be an effective treatment for rheumatoid arthritis (RA), but the pharmacodynamic substances are still unclear. In this study, a four-step strategy integrated nontargeted metabolomics, multivariate statistical analysis, and UNIFI software. An ultrahigh-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was employed to characterize 56 flavonoids from V. coloratum, 25 prototypes and 133 metabolites in biological samples of rats following oral administration of V. coloratum. The endogenous interference peaks in plasma, urine, and feces were reduced by 83.79%, 91.60%, and 86.02%, respectively, through the application of nontargeted metabolomics approaches. The distinctions and commonalities in the flavonoid metabolic pathways of V. coloratum under normal and RA conditions were summarized. Phase II metabolism was significantly affected in the RA rats, especially the prototype exposure and its metabolites in plasma and excreted by urine and feces. Utilizing the aforementioned methods, we identified 109 differential metabolites, including 17 RA-specific metabolites. Twenty-two flavonoid prototypes and their metabolites were identified as potential pharmacodynamic substances in plasma. All the information gained from this study will significantly contribute to elucidating the potential biological and pharmacological mechanisms of flavonoids in V. coloratum, thereby opening new avenues for drug development.