The Oral Bioavailability of 8-Prenylnaringenin from Hops (Humulus Lupulus L.) in Healthy Women and Men is Significantly Higher than that of its Positional Isomer 6-Prenylnaringenin in a Randomized Crossover Trial

Abstract

Scope: Prenylated chalcones and flavonoids from hop (Humulus lupulus L.), such as 6-prenylnaringenin (6-PN) and 8-prenylnaringenin (8-PN), are investigated for their health beneficial and anticancer activities. We, thus, compare the oral bioavailability and safety of 6-PN and 8-PN in healthy young women and men, and investigated their effects on peripheral blood mononuclear cells (PBMC).

Methods and results: A double-blind, placebo-controlled, crossover trial is conducted with 16 healthy volunteers (eight women, eight men) given a single oral dose of 500 mg 6-PN, 8-PN, or placebo in random order. Maximum total concentrations of 6-PN and 8-PN in plasma (C_max ; 543 and 2834 nmol L^-1 ) and their respective area under the plasma concentration-time curve (AUC; 3635 and 15801 nmol L^-1 × h) are significantly (5.2- and 4.3-fold) higher for 8-PN than for 6-PN (p ˂ 0.05). PBMC for ex vivo experiments are isolated from blood sampled before and 6 h after intake of 6-PN, 8-PN, or placebo. Despite the single-treatment regime and low blood concentrations, both 6-PN and 8-PN increase the survival of PBMC relative to control.

Conclusion: 8-PN is significantly more bioavailable in healthy humans than its isomer 6-PN. Interestingly, 6-PN, despite being less bioavailable, is similarly effective as 8-PN in enhancing PBMC viability.

Trial registration: ClinicalTrials.gov NCT03140397.

Keywords: human study; immune cells; peripheral blood mononuclear cells; pharmacokinetics; prenylflavonoids.