Effects of Hesperidin Consumption on the Cardiovascular System in Pre- and Stage 1 Hypertensive Subjects: Targeted and Non-Targeted Metabolomic Approaches (CITRUS Study)

Mol Nutr Food Res. 2021 Sep;65(17):e2001175. doi: 10.1002/mnfr.202001175. Epub 2021 Aug 2.

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.

Keywords: hesperidin; hypertensive; metabolomic analysis; orange juice; plasma; urine.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Biomarkers / urine
  • Citrus sinensis / chemistry*
  • Female
  • Fruit and Vegetable Juices
  • Glucuronides / blood
  • Glucuronides / urine
  • Hesperidin / analogs & derivatives
  • Hesperidin / blood
  • Hesperidin / metabolism
  • Hesperidin / pharmacology*
  • Hesperidin / urine
  • Humans
  • Hypertension / diet therapy*
  • Hypertension / metabolism
  • Male
  • Metabolomics / methods
  • Middle Aged
  • Postprandial Period

Substances

  • Biomarkers
  • Glucuronides
  • hesperetin-7-O-glucuronide
  • Hesperidin