Pharmacokinetics and tissue disposition of urolithin A, an ellagitannin‐derived metabolite, in mice

Ellagitannins (ETs) are bioactive polyphenols present in some fruits (pomegranates, strawberries, red and black raspberries) and nuts (almonds, walnuts). Once consumed, ETs hydrolyze and are absorbed as ellagic acid which rapidly clears from plasma over 5 h. Ellagic acid is further metabolized by liver enzymes and gut microflora into 1,6-hydroxybenzopyran derivatives (or urolithins). However the pharmacokinetics and tissue disposition of urolithins has not been reported. Therefore we synthesized and intraperitoneally (i.p.) or orally administered urolithin A (UA) to B6 mice. Blood (over 24 h) and tissues (prostate, liver, kidney, lung, colon, intestine, brain) were collected and analyzed for UA and its conjugates by high performance liquid chromatography mass spectrometry. Metabolite levels were UA >UA-sulphate>UA-glucuronide>methylated-UA; all metabolites cleared by 24 h. UA concentration was highest in mouse prostate tissues by the oral route, and in colon and prostate tissues by the i.p. route. Only methlyated-UA was detected in brain tissues. Administration by i.p. resulted in shorter Tmax (2 h) and higher concentrations than oral administration (Tmax, 4 h). Given that the mouse prostate gland was a main target tissue of concentration by UA, and the previous report of the effects of pomegranate juice on prostate cancer patients, further human bioavailability studies are warranted.