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Study On Metabolism Of Main Flavonoids From Epimedium

Posted on:2020-05-29Degree:MasterType:Thesis
Country:ChinaCandidate:L GaoFull Text:PDF
GTID:2404330602960945Subject:Pharmacy
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Objective:1.Using human hepatocyte microsomal incubation system to investigate the metabolism of Epimedin A?Epimedin B?Epimedin C and Icariin in vitro:2.To study the metabolic pathways of Epimedin B in rat' s feces and urine;3.To explore the difference metabolism of Epimedin B between in vivo and in vitro;Methods:1.Identified of metabolites in vitro:ThermoQ-Exactive was applied to systemically analyze the Epimedin A?Epimedin B?Epimedin C and Icari in metabolism in the liver microsomes of human.2.Identified of metabolitesin in vivo;12 Sprague Dawley rats were classed to 2 groups,corresponding to a blank control group,an intermuscular administration and an oral administration group.Rat feces and urine sample were collected at 24 h after administration.All samples were pretreated and analyzed by LC-LTQ Orbitrap MSn.Results:1.Analyzed by the accurate relative molecular mass and fragment ion information,Twenty-eight metabolites were obtained from in vitro experiments samples,four new metabolites were identified.Their possible metabolic pathways and possible chemical structures were elucidated.2.By comparison with the total ion chromatogram of samples from the blank control group,the possible metabolites in the samples of drug-treated group could be preliminarily screened.These metabolites were further analyzed by multistage product ion scanning and comparison with the retention time with those of reference substances.As a result eleven metabolites epimedin B were identified in rat,and four of them were fist indentified as new metabolites.Their main possible metabolic pathways and possible structures were elucidated.Conclusion:1.First report of Epimedium Metabolism in vitro,metabolic pathways of four compounds are similar in vitro.Hydrolysis,oxidation,methylation and demethylation were found to be the major metabolic pathway of epimedin A?epimedin B?epimedin C and icariin in Human Liver Microsomes.2.Combination,hydrolysis,oxydation and demethylation were found to be the major metabolic pathway of epimedin B in rats.3.The metabolic pathways of epimedin B were difference between in vitro and in vivo,Metabolites are also different.
Keywords/Search Tags:Epimedium, liquid chromatography tandem mass spectrometry, metabolic transformation in vivo, Human Liver Microsomes, metabolic transformation in vitro
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