Absorption, Metabolism, and Excretion of Cajaninstilbene Acid

Cajaninstilbene acid (CSA), an active stilbene isolated from the leaves of pigeon pea (Cajanus cajan), exhibits several bioactivities. To develop CSA as a potential nutraceutical and provide pharmacokinetic foundations for its further <i>in vivo</i> bioactivity studies, this study aims to explore its absorption, metabolism, and excretion systematically. Human colon adenocarcinoma (Caco-2) cell monolayers were utilized to investigate the CSA transport mechanism. CSA metabolites were identified in rat biological samples and quantified to explore their excretion routes. CSA exhibited a high permeability and was transported across Caco-2 monolayers mainly by passive transport via the transcellular process. Four new CSA metabolites were found <i>in vivo</i>, namely, CSA-2-<i>COO</i>-glucuronide, 6,12-dihydroxy CSA, 3-hydroxy-5-methoxystilbene-3-<i>O</i>-glucuronide, and 6-hydroxy CSA-3-<i>O</i>-glucuronide, in addition to our previously reported metabolite CSA-3-<i>O</i>-glucuronide. These metabolites were mainly excreted in bile. Our results indicate that metabolism but not absorption is the major barrier limiting the oral bioavailability of CSA.