Absorption and biotransformation of α‐mangostin by nude mice without and with HT‐29 colon cancer xenograft

Abstract

Alpha‐mangostin (α‐MG) is the most abundant xanthone in mangosteen fruit. Anti‐cancer activities such as anti‐oxidant, anti‐proliferative/pro‐apoptotic, and anti‐inflammatory activities of α‐MG have been demonstrated in vitro and in rodents. However, the absorption and metabolism of α‐MG and other xanthones is limited. We examined in vivo absorption and metabolism of α‐MG in mice with and without HT‐29 colon cancer xenografts; mice were fed AIN‐93 diet containing 0.1% α‐MG (95% of total xanthones). Serum, liver, tumor and feces were collected after 3 and 5 weeks of feeding. Free and conjugated (glucuronides/sulfates) species of α‐MG were detected in liver (2.0 μg/g α‐MG with 50% conjugates in control liver; 3.7 μg α‐MG/g with 78% conjugates in liver of tumor bearing mice), tumor (3.6 μg α‐MG/g; 53% conjugates) and serum. Notably, the most abundant xanthone species in liver appeared to be a novel xanthone dimer according to accurate mass measurements. Apparent minor metabolites of α‐MG included methylated/demethylated, hydrated, oxidized/reduced and pyrano‐forms. Although suggestive of extensive metabolism of α‐MG, it is possible that minor xanthones were absorbed and accumulated by specific tissues. These data support the use of murine models to characterize metabolic processes relevant to the study of biological activities of xanthones in humans.Grant Funding Source : OSU Food Innovation Center, Molecular Carcinogenesis and Chemoprevention, Center for Advanced Functional Foods Research and Enterpreneurship and Nutrient and Phytochemical Analytic Shared Resource