title: R(-)-O-desmethylangolensin is the main enantiomeric form of daidzein metabolite produced by human in vitro and in vivo.
abstract: After ingestion, human intestinal bacteria transform daidzein into dihydrodaidzein, which can be further metabolised to O-desmethylangolensin. This metabolite, unlike daidzein, has a chiral centre and can therefore occur as two distinct enantiomers; however, it is unclear which enantiomer is present in humans. The aim of this study was to define in vitro and in vivo the structure of O-desmethylangolensin and then to evaluate its pharmacokinetic parameters. Daidzein metabolism was preliminarily investigated in anaerobic batch cultures inoculated with mixed faecal bacteria from O-desmethylangolensin producer volunteers. The transformation was monitored by liquid chromatography-mass spectrometry and a chiral column was used to distinguish dihydrodaidzein and O-desmethylangolensin enantiomers. These were purified, analysed by circular dichroism and the results established R(-)-O-desmethylangolensin as the main product (enantiomer excess 91%). However, both dihydrodaidzein enantiomers were detected. Similar results were obtained by in vivo trials. The in vitro formation of O-desmethylangolensin seems to be directly correlated with the number of transforming microorganisms. This correlation was found in vivo for tmax but not for other pharmacokinetic indexes. The pharmacokinetics of daidzein, dihydrodaidzein and O-desmethylangolensin were then evaluated in 11 healthy adult O-desmethylangolensin producers after the single administration of soy milk containing 100mg daidzein. The conjugated forms of daidzein, dihydrodaidzein and O-desmethylangolensin represent more than 90 and 95% of the plasmatic and urinary forms, respectively. The Cmax, tmax and half-life of O-desmethylangolensin in plasma were 62±53nM, 28±11 and 15±6h, respectively. Relevant inter-individual variations were observed as indicated by the high standard deviations.
authors.affiliation: Università degli Studi di Milano - Department of Food, Environmental and Nutritional Sciences - DeFENS, Division of Human Nutrition - Via Celoria 2, 20133 Milan, Italy. Electronic address: claudio.gardana@unimi.it.
authors.forename: Claudio
authors.initials: C
authors.lastname: Gardana
authors.affiliation: Università degli Studi di Milano - Department of Food, Environmental and Nutritional Sciences - DeFENS, Division of Microbiology - Via Celoria 2, 20133 Milan, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Canzi
authors.affiliation: Università degli Studi di Milano - Department of Food, Environmental and Nutritional Sciences - DeFENS, Division of Human Nutrition - Via Celoria 2, 20133 Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Simonetti
mesh_terms: D000328:Adult; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D006801:Humans; D007529:Isoflavones / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000652:urine; D064307:Microbiota; D008875:Middle Aged; D013237:Stereoisomerism; D053719:Tandem Mass Spectrometry
chemical_list: D007529:Isoflavones; C004742:daidzein; C050052:O-desmethylangolensin
keywords: Daidzein metabolism; Human; Microflora; ODMA enantiomers; Pharmacokinetics