RESUMEN
The ß-carboline alkaloids, harmaline and harmine, are present in hallucinogenic plants Ayahuasca and Peganum harmala, and in a variety of foods. In order to establish the metabolic pathway and bioactivities of endogenous and xenobiotic bioactive ß-carbolines, high-performance liquid chromatography, coupled with mass spectrometry, was used to identify these metabolites in human liver microsomes (HLMs) in vitro and in rat urine and bile samples after oral administration of the alkaloids. Three metabolites of harmaline and two of harmine were found in the HLMs. Nine metabolites for harmaline and seven metabolites for harmine, from the rat urine and bile samples, were identified. Among them, four in vivo metabolites were isolated and fully characterised by NMR analysis. For the first time, harmaline is shown transforming to harmine by oxidative dehydrogenation in rat. Five metabolic pathways were therefore proposed, namely, oxidative dehydrogenation, 7-O-demethylation, hydroxylation, O-glucuronide conjugation and O-sulphate conjugation.
Asunto(s)
Banisteriopsis/metabolismo , Carbolinas/metabolismo , Medicamentos Herbarios Chinos/metabolismo , Harmalina/metabolismo , Harmina/metabolismo , Peganum/metabolismo , Animales , Banisteriopsis/química , Carbolinas/química , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Harmalina/química , Harmina/química , Humanos , Espectroscopía de Resonancia Magnética/métodos , Masculino , Estructura Molecular , Peganum/química , Ratas , Ratas Sprague-Dawley , Espectrometría de Masa por Ionización de Electrospray/métodos , Orina/químicaRESUMEN
Two new compounds, including petasinoside A and chloridate-[N-chloromethyl-hectorine], were isolated from Senecio nemorensis. The structures of these compounds were elucidated by spectroscopic methods including 1D and 2D NMR experiments.