Metabolites Identification of Two Novel Chemical Constituents From Melia. Toosendan Sieb.et Zucc. in Rats by UPLC/ESI/qTOF-MS Analysis

Melia. toosendan Sieb.et Zucc., a potent herbal medicine, boasts diverse therapeutic properties. As the main components, the isotoosendanin blocks protective autophagy in chemotherapy-induced cultured cancer cells and xenograft tumor tissue to significantly enhancing anticancer activity, and the fraxinellone contributes to pesticidal activity, anti-inflammatory and immunomodulatory effects. Until now, the metabolic profiles remained unknown. In the present study, 13 metabolites of isotoosendanin and 13 metabolites of fraxinellone were characterized in the blood, urine, and feces of rats by UPLC/ESI/qTOF-MS analysis. Five metabolites (F-M3, F-M5, I-M1, I-M5, I-M8) were fully characterized. The isotoosendanin and fraxinellone were mainly involved in hydrogenation, acetylation, and methylenation metabolic reactions. This is the first study illuminates the two components in vivo metabolism, laying the foundation for future pharmacodynamic and mechanistic investigations. It is necessary to deeply understand the process of drug activation, and deactivation, rationally design new drugs, and guide the research and development of new drugs.