title: Human serum determination and in vitro anti-inflammatory activity of the vitamin E metabolite α-(13'-hydroxy)-6-hydroxychroman.
abstract: Cytochrome P450-derived long-chain metabolites are gaining increasing interest as bioactive intermediates of vitamin E. In this study we first report on the HPLC-ECD and GC-MS analysis in human serum of the earliest metabolite of this vitamin, namely α-(13'-hydroxy)-6-hydroxychroman (α-13'-OH). The two chromatographic procedure are sensitive enough (LOQ of 10nM) to measure α-13'-OH after hexane extraction of 1 ml of sample obtained from healthy volunteers supplemented for 1-week with 1000 IU/d (671 mg/d) RRR-α-tocopherol. The observed concentrations ranged between 15 and 50 nM, with minor differences between fasting and 4-hr post-meal state. Baseline (non-supplemented state) levels of 7.2 ± 1.6 nM were observed extracting higher volumes of serum. Biological effects of α-13'-OH investigated for the first time in RAW264.7 murine macrophages involved transcriptional control of inflammatory cytokines, and transcriptional and functional regulation of COX2 and iNOS enzymes in response to lipopolysaccharides. In conclusion, here we present the first quantitative evaluation of serum α-13'-OH also providing early evidence of the anti-inflammatory potential of this metabolite that is worth of further investigation in the area of functional and nutraceutical implications of vitamin E metabolism.
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Ciffolilli
authors.affiliation: Institute of Nutrition, Friedrich Schiller University Jena, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Wallert
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Italy.
authors.forename: Desirée
authors.initials: D
authors.lastname: Bartolini
authors.affiliation: Institute of Pharmacy, Friedrich Schiller University Jena, Germany.
authors.forename: Verena
authors.initials: V
authors.lastname: Krauth
authors.affiliation: Institute of Pharmacy, Friedrich Schiller University Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Piroddi
authors.affiliation: Department of Chemistry, Biology and Biotechnology, University of Perugia, Italy.
authors.forename: Bartolomeo
authors.initials: B
authors.lastname: Sebastiani
authors.affiliation: Institute of Nutrition, Friedrich Schiller University Jena, Germany; Institute of Nutrition, Friedrich Schiller University Jena, Germany.
authors.forename: Pierangelo
authors.initials: P
authors.lastname: Torquato
authors.affiliation: Institute of Nutrition, Friedrich Schiller University Jena, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Lorkowski
authors.affiliation: Department of Nutritional, Food and Consumer Studies, University of Applied Sciences Fulda, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Birringer
authors.affiliation: Department of Pharmaceutical Sciences, University of Perugia, Italy. Electronic address: francesco.galli@unipg.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Galli
mesh_terms: D000328:Adult; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000097:blood* / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D066298:In Vitro Techniques; D018836:Inflammation Mediators; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D024505:Tocopherols / Q000097:blood* / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D024505:Tocopherols
keywords: CYP4F2; Cytochrome P-450; Cytokines; Inflammation; Long-chain metabolites; Tocopherol; Vitamin E; α-13’-OH