title: Targeted and Untargeted Metabolomics to Explore the Bioavailability of the Secoiridoids from a Seed/Fruit Extract (Fraxinus angustifolia Vahl) in Human Healthy Volunteers: A Preliminary Study.
abstract: The bark, seeds, fruits and leaves of the genus Fraxinus (Oleaceae) which contain a wide range of phytochemicals, mostly secoiridoid glucosides, have been widely used in folk medicine against a number of ailments, yet little is known about the metabolism and uptake of the major Fraxinus components. The aim of this work was to advance in the knowledge on the bioavailability of the secoiridoids present in a Fraxinus angustifolia Vahl seed/fruit extract using both targeted and untargeted metabolomic analyses. Plasma and urine samples from nine healthy volunteers were taken at specific time intervals following the intake of the extract and analyzed by UPLC-ESI-QTOF. Predicted metabolites such as tyrosol and ligstroside-aglycone glucuronides and sulfates were detected at low intensity. These compounds reached peak plasma levels 2 h after the intake and exhibited high variability among the participants. The ligstroside-aglycone conjugates may be considered as potential biomarkers of the Fraxinus secoiridoids intake. Using the untargeted approach we additionally detected phenolic conjugates identified as ferulic acid and caffeic acid sulfates, as well as hydroxybenzyl and hydroxyphenylacetaldehyde sulfate derivatives which support further metabolism of the secoiridoids by phase I and (or) microbial enzymes. Overall, the results of this study suggest low uptake of intact secoiridoids from a Fraxinus angustifolia Vahl extract in healthy human volunteers and metabolic conversion by esterases, glycosidases, and phase II sulfo- and glucuronosyl transferases to form smaller conjugated derivatives.
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department Food Science and Technology, Centro de Edafología y Biología Aplicada del Segura (CEBAS)-Consejo Superior de Investigaciones Científicas (CSIC), P. O. Box 164, Campus de Espinardo, Murcia 30100, Spain. rgvillalba@cebas.csic.es.
authors.forename: Rocío
authors.initials: R
authors.lastname: García-Villalba
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department Food Science and Technology, Centro de Edafología y Biología Aplicada del Segura (CEBAS)-Consejo Superior de Investigaciones Científicas (CSIC), P. O. Box 164, Campus de Espinardo, Murcia 30100, Spain. fatomas@cebas.csic.es.
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Tomás-Barberán
authors.affiliation: Naturex SA, Site d'AgroParc, BP 1218, 84911 Avignon Cedex 9, France. p.fancaberthon@naturex.com.
authors.forename: Pascale
authors.initials: P
authors.lastname: Fança-Berthon
authors.affiliation: Naturex SA, Site d'AgroParc, BP 1218, 84911 Avignon Cedex 9, France. m.roller@naturex.com.
authors.forename: Marc
authors.initials: M
authors.lastname: Roller
authors.affiliation: Department of Food Technology and Nutrition, Catholic University of San Antonio, Campus de los Jerónimos, N° 135, Guadalupe, Murcia 30107, Spain. mpzafrilla@ucam.edu.
authors.forename: Pilar
authors.initials: P
authors.lastname: Zafrilla
authors.affiliation: Naturex Spain SL, Autovia A3, Salida343, Camino de Torrent s/n, Quart de Poblet, Valencia 46930, Spain. n.issaly@naturex.com.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Issaly
authors.affiliation: Research Group on Quality, Safety and Bioactivity of Plant Foods, Department Food Science and Technology, Centro de Edafología y Biología Aplicada del Segura (CEBAS)-Consejo Superior de Investigaciones Científicas (CSIC), P. O. Box 164, Campus de Espinardo, Murcia 30100, Spain. mtconesa@cebas.csic.es.
authors.forename: María-Teresa
authors.initials: MT
authors.lastname: García-Conesa
mesh_terms: D000328:Adult; D001682:Biological Availability; D001711:Biotransformation; D002109:Caffeic Acids / Q000302:isolation & purification; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003373:Coumaric Acids / Q000302:isolation & purification; D005260:Female; D031661:Fraxinus / Q000737:chemistry*; D005638:Fruit / Q000737:chemistry*; D005960:Glucosides / Q000097:blood* / Q000652:urine; D020719:Glucuronides / Q000097:blood* / Q000652:urine; D064368:Healthy Volunteers; D006801:Humans; D062385:Hydroxybenzoates; D039823:Iridoids / Q000097:blood* / Q000652:urine; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry; D011714:Pyrans / Q000097:blood* / Q000652:urine; D012639:Seeds / Q000737:chemistry*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013431:Sulfates
chemical_list: D002109:Caffeic Acids; D003373:Coumaric Acids; D005960:Glucosides; D020719:Glucuronides; D062385:Hydroxybenzoates; D039823:Iridoids; D010936:Plant Extracts; D011714:Pyrans; D013431:Sulfates; C445380:ligstroside; C004999:ferulic acid; C040048:caffeic acid
keywords: UPLC-ESI-QTOF; absorption; ligstroside-aglycone; metabolism; phase II conjugation; tyrosol