狼毒大戟中4种二萜类成分在大鼠肝微粒体中的代谢

目的 研究狼毒大戟中4种二萜类成分在大鼠肝微粒体中的代谢产物并探讨其代谢规律.方法 运用大鼠肝微粒体体外孵育法,将岩大戟内酯A、岩大戟内酯B、17-羟基岩大戟内酯A、17-羟基岩大戟内酯B加至由还原型烟酰胺腺嘌呤二核苷酸磷酸启动的大鼠肝微粒体孵育体系中,于37℃条件下孵育30 min,再用乙腈终止反应.以阴性组(先加乙...

Metabolism of four diterpenoids of Euphorbia fischeriana in liver microsomes of rats

OBJECTIVE To study the metabolites of four diterpenoids of Euphorbia fischeriana in liver microsomes of rats and to investigate its metabolic regularity.METHODS In vitro incubation system of liver microsomes of rats was built.The jolkinolide A,jolkinolide B,17-hydroxyl jolkinolide A and 17-hydroxyl jolkinolide B were added into incubation system of liver microsomes in rats activated by reduced nicotinamide adenine dinucleotide phosphate,incubated at 37℃for 30 min,and then terminated the reaction with acetonitrile.Taking the negative group(adding acetonitrile firstly and then starting incubation for 30 min)as the reference,the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used;Anaylyst^■TF 1.7.1、PeakView^■2.2,MetabolitePilot 1.5 and MasterView 1.2 software were used to speculate and identify the fragmentation law of mass spectrometry and metabolites.RESULTS Four diterpenoids were easy to lose neutral fragments such as H₂O and CO in secondary mass spectrometry.Jolkinolide A and 17-hydroxyl jolkinolide A showed similar metabolism pathway,including dihydroxylation,dehydrogenation,and monohydroxylation;six and five metabolites were identified respectively.Jolkinolide B and 17-hydroxyl jolkinolide B showed similar metabolism pathway,including monohydroxylation,hydration and isomerization.Five metabolites were identified.CONCLUSIONS Both jolkinolide A and 17-hydroxyl jolkinolide A produce the metabolites of hydroxylation and dehydrogenation in liver microsomes of rats;both jolkinolide B and 17-hydroxyl jolkinolide B produce the metabolites of hydroxylation,hydration and isomerization in liver microsomes of rats.The metabolites of four diterpenoids are phaseⅠmetabolites.