Potential modulation on BCRP and MRP 4 by onion: in vivo and ex-vivo studies

Onion skin contains quercetin, kaempferol and their glycosides. Methotrexate (MTX), an immunosuppressant with narrow therapeutic window, is used as a probe substrate of BCRP and MRP 4. This study investigated the effect of onion skin powder (OSP) on MTX pharmacokinetics. Rats were orally administered MTX with and without OSP. The serum concentration of MTX was determined by fluorescence polarization immunoassay. Our results showed that after coadministration of 0.5 g/kg of OSP the AUC0-3600 and MRT of MTX were significantly increased by 222% and 101%, whereas 1.0 g/kg of OSP significantly increased them by 126% and 82%, respectively. Cell studies showed that OSP metabolites inhibited the functions of BCRP and MRP 4, whereas OSP activated BCRP. Thus concomitant intake of onion skin increased the systemic exposure and toxicity of MTX through inhibition on BCRP and MRP 4.