Effect of Flavonoid and Triterpenoid Compounds on the Function of Organic Anion Transporting Polypeptide 1B3 / 中国药学杂志

ABSTRACT

OBJECTIVEP To investigate the effect of flavonoids and triterpenoids on the function of organic anion transporting polypeptide 1B3. METHODS: Natural products such as flavonoids and triterpenoids are widely present in traditional Chinese medicine and daily diets. In the present study, CHO cells stably expressing OATP1B3 and its fluorescent substrate fluorescein methotrexate were employed to investigate the effect of 21 natural products on the function of OATP1B3. RESULTS: Mulberrin, glycyrrhetinic acid, glycyrrhizic acid, quercitrin, quercetin, and chrysanthemum stem-leaf flavonoids showed significant inhibitory effects on OATP1B3-mediated uptake of fluorescein methotrexate, with IC50 values being of 3.6, 3.8, 7.5, 9.0, 10.1 μmol•L-1, and 4.1 μg•mL-1, respectively. The IC50 value of glycyrrhetinic acid on OATP1B3 was comparable to its blood concentration in clinics, indicating an OATP1B3-mediated drug-drug interaction could occur. CONCLUSION: Some flavonoids and triterpenoids are OATP1B3 inhibitors. When patients take medications of OATP1B3 substrates, care should be taken to avoid coadmistration of drugs or food containing these inhibitors to circumvent the occurrence of adverse drug interactions.