- Article
16 Pages
Background: Silymarin is widely used as a hepatoprotective and nephroprotective agent. However, its potential to interact with renal organic anion transporters (OATs) remains poorly understood. This study investigated the effects of silymarin and its major constituent, silybin, on the transport functions of human (h) OAT1 and hOAT3 and transporter-mediated drug accumulation. Methods: Interactions and mechanisms of silymarin with hOAT1 and hOAT3 were studied using MDCK cells stably expressing hOAT1 or hOAT3. Results: Silymarin significantly inhibited hOAT1- and hOAT3-mediated transport in a concentration-dependent manner, with IC50 values of 0.32 and 0.65 µg/mL, respectively. Silybin also inhibited both transporters but exhibited lower potency, with IC50 values of 3.02 µg/mL for hOAT1 and 8.5 µg/mL for hOAT3. Kinetic studies demonstrated increased Kt values without changes in Jmax, indicating competitive inhibition. Molecular docking revealed strong binding affinities of multiple silymarin constituents toward the substrate-binding pockets of both transporters, supporting a competitive interaction mechanism. Functionally, silymarin significantly reduced accumulation of tenofovir, an OAT substrate drug. Consistently, silymarin attenuated tenofovir-induced cytotoxicity in hOAT1- and hOAT3-expressing cells, with a greater protective effect observed in hOAT1 cells. Conclusions: These findings indicate that silymarin inhibits hOAT1 and hOAT3 and highlight the potential for both transporter-mediated silymarin–drug interactions.
J. Xenobiotics
23 October 2026






![Traffic light plot for the included studies [7,18,19,20,21,22,23,24,25,26,27,28,29,30] assessed using the ROBINS-E tool [14,15].](https://mdpi-res.com/jox/jox-16-00131/article_deploy/html/images/jox-16-00131-g001-550.jpg)

