Fisetin disposition and metabolism in mice: Identification of geraldol as an active metabolite

Fisetin's anticancer activity in mice was well documented by 2011, but nobody had characterised what actually happens to it in the body — how fast it's cleared, and what it turns into.

This French team gave mice a single anticancer-effective dose of fisetin and tracked it and its breakdown products in blood and in Lewis lung tumours, then tested the main new metabolite they found, called geraldol, side-by-side with fisetin itself.

Fisetin was cleared from plasma very quickly (terminal half-life about 3.1 hours) and extensively converted to glucuronide conjugates, but one previously uncharacterised metabolite — geraldol, a methoxylated form of fisetin — reached higher concentrations than fisetin itself inside the tumours, and turned out to be more cytotoxic to cancer cells and better at blocking endothelial cell migration than the parent compound.

Bottom line: this reframes fisetin's anticancer activity in mice as partly mediated by an active metabolite rather than fisetin alone — relevant to interpreting any oral fisetin pharmacokinetics or dosing claims, though this is a single-dose mouse study.