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.

Rocío García-Villalba,Francisco Tomás-Barberán,María-Teresa García-Conesa,Pilar Zafrilla,Nicolas Issaly,Pascale Fança-Berthon,Marc Roller

doi:10.3390/molecules201219845

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.

Highlights

We confirmed that the two major polyphenolic components, the secoiridoid glucosides nuzhenide and GL3, were present and amounted up to 5.92% ̆ 0.14% and 4.75% ̆ 0.09%, respectively
Various other compounds were detected in the extract based on their mass [M H] ́, the MS/MS fragmentation pattern and data available in the literature (Table 1) [1,4]
These compounds contain as part of their molecular structure: tyrosol (4-hydroxyphenyl ethylalcohol), elenolic acid and elenolic acid linked to tyrosol (Figure 1)

Summary

Introduction

The genus Fraxinus (Oleaceae) which contains a wide range of phytochemicals, mostly secoiridoid glucosides, coumarins and phenylethanoids, and some flavonoids, benzoquinones, indole derivatives and simple phenolics has been commonly used in traditional medicine against various inflammatory diseases, infections, constipation, as a diuretic and as a hepatoprotective agent [M1o]l.ecuAlesd20d1i5t,i2o0,npaalgley–,paagne extract produced from the seeds/fruits of Fraxinus has been shown to moderate body weight gain, body fat, glucose and insulin levels, fatty liver incidence as well as blood pressudreiseinasevsa, riinofuecstioannsi,mcaonl smtipoadtieolns, oafs oabedsiuitrye,tidc iaanbdetaess aanhdephaytopperrotteecntsivioe nag[e2n–t5][1s].upApdodrittiionngalplyo, tential beneficainalexptrroacpteprrtoiedsucoefdFfrroaxminthues saegedasin/fsrut imtseotfaFbroaxliincudsihsaosrdbeeerns.shTohwensetobmenodefiercaitaelbeofdfeycwtseiwghetregaoinb,served with dbmoosodedyselfsraato,nfgoglbuinecsogistyeb,aedntiwadbeienetesnus lai1nn0d0lehvayenplsed,rftae2nt0tsy0iolmniv[eg2r–ip5n]ecsirudpeknpgcoerotaifnsgbwopedoltlyeanswtibaelloibgoehdntepfpirceeisarslupdrreaoypin,ercvtoiaerrsirooeufssFpraoanxniimdnuiansl g to a HumanagaEiqnustivmaelteanbot liDc odsiseor(dHeErsD.

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