L Pla-Pagà1,2, A Pedret1,2, R M Valls1,2, L Calderón-Pérez1,2, E Llauradó2, J Companys1,2, F Martín-Luján2,3,4, A Moragas2,3,5, N Canela1,6, F Puiggròs1, A Caimari1, J M Del Bas1, L Arola1, R Solà1,2,7, J Mayneris-Perxachs1,8. 1. Eurecat, Centre Tecnològic de Catalunya, Unitat de Nutrició i Salut, Reus, Spain. 2. Facultat de Medicina i Ciències de la Salut, Functional Nutrition, Oxidation and Cardiovascular Disease Group (NFOC-Salut), Universitat Rovira i Virgili, Reus, Spain. 3. Institut Universitari d'Investigació en Atenció Primària-IDIAP Jordi Gol, Tarragona, Spain. 4. Primary Care Centre Sant Pere, Institut Català de la Salut, Tarragona, Spain. 5. Primary Care Centre Jaume I, Institut Català de la Salut, Tarragona, Spain. 6. Eurecat, Centre Tecnològic de Catalunya, Centre for Omic Science, Reus, Spain. 7. Hospital Universitari Sant Joan, Reus, Spain. 8. Department of Endocrinology, Diabetes and Nutrition, Dr Josep Trueta University Hospital, Girona Biomedical Research Institute (IDIBGI), Girona, Spain.
Abstract
SCOPE: The aim of the present work is to determine new biomarkers of the biological effects of hesperidin in orange juice (OJ) applying a non-targeted metabolomics approach validated by targeted metabolomics analyses of compliance biomarkers. METHODS AND RESULTS: Plasma/serum and urine targeted (HPLC-MS/MS) and untargeted (1 H-NMR) metabolomics signatures are explored in a subsample with pre- and stage-1 hypertension subjects of the CITRUS study (N = 159). Volunteers received 500 mL day-1 of control drink, OJ, or hesperidin-enriched OJ (EOJ) for 12-weeks. A 6-h postprandrial study is performed at baseline. Targeted analyses reveals plasma and urine hesperetin 7-O-β-d-glucuronide as the only metabolite differing between OJ and EOJ groups after 12-weeks consumption, and in urine is correlated with a decreased systolic blood pressure level. The non-targeted approach shows that after single dose and 12-weeks consumption of OJ and EOJ change several metabolites related with an anti-inflammatory and antioxidant actions, lower blood pressure levels and uremic toxins. CONCLUSIONS: Hesperetin 7-O-β-d-glucuronide can be a candidate marker for distinguishing between the consumption of different hesperidin doses at 12-weeks consumption as well as a potential agent mediating blood pressure reduction. Moreover, changes in different endogenous metabolites can explain the mechanisms of action and the biological effects of hesperidin consumption.
SCOPE: The aim of the present work is to determine new biomarkers of the biological effects of hesperidin in orange juice (OJ) applying a non-targeted metabolomics approach validated by targeted metabolomics analyses of compliance biomarkers. METHODS AND RESULTS: Plasma/serum and urine targeted (HPLC-MS/MS) and untargeted (1 H-NMR) metabolomics signatures are explored in a subsample with pre- and stage-1 hypertension subjects of the CITRUS study (N = 159). Volunteers received 500 mL day-1 of control drink, OJ, or hesperidin-enriched OJ (EOJ) for 12-weeks. A 6-h postprandrial study is performed at baseline. Targeted analyses reveals plasma and urine hesperetin 7-O-β-d-glucuronide as the only metabolite differing between OJ and EOJ groups after 12-weeks consumption, and in urine is correlated with a decreased systolic blood pressure level. The non-targeted approach shows that after single dose and 12-weeks consumption of OJ and EOJ change several metabolites related with an anti-inflammatory and antioxidant actions, lower blood pressure levels and uremic toxins. CONCLUSIONS: Hesperetin 7-O-β-d-glucuronide can be a candidate marker for distinguishing between the consumption of different hesperidin doses at 12-weeks consumption as well as a potential agent mediating blood pressure reduction. Moreover, changes in different endogenous metabolites can explain the mechanisms of action and the biological effects of hesperidin consumption.