In vitro absorption and metabolism of isoflavone C-glycosides, O-glycosides, and their aglycons

Isoflavones are a class of phytochemicals predominantly found in members of the Fabaceae family, particularly in leguminous plants such as soybeans, clover, and beans [ 1 ]. Their potential health-promoting effects have garnered considerable scientific interest in recent years, especially regarding their role as alternative therapeutic agents in the prevention and management of cancer, cardiovascular diseases, and menopausal disorders [ 2 ]. The extent of isoflavones’ biological activity in humans is critically influenced by their absorption and metabolic transformation, primarily occurring in the small intestine and liver. Accordingly, this project aimed to establish an in vitro model capable of predicting the oral bioavailability of isoflavones with special emphasis on their C -glycosides. Based on the absorption in a Caco-2 cell model, the permeability coefficients of the compounds were determined ([ Fig. 1A ]). In addition, the scaled intrinsic clearance rates were calculated based on the absorption of the compounds in the HepaRG™ cell model ([ Fig. 1B ]). By calibrating the experiments with well-investigated model substances (sulpiride, furosemide, propranolol, phenacetin, and fluphenazine), these results could be correlated to in vivo intestinal absorption and hepatic clearance. Moreover, numerous intestinal and hepatic metabolites were detected using UHPLC-DAD-MS. The formation of metabolites was verified using control substances with known in vivo metabolites. Thereby, a wide range of phase I and phase II metabolites was identified for the isoflavones. In addition, the associated aglycons could also be detected as metabolites for the C-glycosides, which indicates that both Caco-2 and HepaRG™ cells can cleave C-C bonds. Fig. 1 Apparent permeability coefficients and scaled intrinsic clearance rates of isoflavones compared to control compounds. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany