Absorption, distribution, metabolism and excretion of apigenin and its glycosides in healthy male adults

The bioavailability of apigenin and its O-glycosides in humans was investigated with apigenin-4′-glucuronide (Ap-4′-GlcUA), apigenin-7-glucuronide and apigenin-7-sulfate being identified as in vivo metabolites. Apigenin per se was poorly absorbed with metabolites equivalent to 0.5% of intake excreted in urine 0–24 h post-intake. Consumption of a parsley drink containing apigenin-7-O-(2″-O-apiosyl)glucoside resulted in the peak plasma concentration (Cmax) of Ap-4′-GlcUA occurring after 4 h, indicative of absorption in the lower gastrointestinal tract (GIT). Urinary excretion of the three metabolites corresponded to 11.2% of intake. Ingestion of dried powdered parsley leaves with yogurt extended the Cmax of Ap-4′-GlcUA to 6 h. Consumption of chamomile tea containing apigenin-7′-O-glucoside resulted in a 2 h Cmax of Ap-4′-GlcUA, in keeping with absorption in the upper GIT. Urinary excretion was equivalent to 34% of intake. Intake of the parsley drink provided information on intra- and inter-individual variations in the level of excretion of the apigenin metabolites. This trail was registered at clinicaltrials.gov as NCT03526081. [Display omitted] •Human absorption and metabolism of apigenin and its glycosides.•Identification of apigenin metabolites in plasma and urine.•Plasma pharmacokinetics and urinary excretion of apigenin metabolites.•Impact of sugar moiety on apigenin absorption.•Essential data for ex vivo tissue studies using apigenin metabolites.