[The interactions between natural products and OATP1B1]
Yao Xue Xue Bao = Acta Pharmaceutica Sinica
|November 11, 2015
Summary
Natural compounds like flavonoids and triterpenoids can inhibit the liver transporter OATP1B1, potentially causing drug interactions. Their activity depends on structure and sugar modifications, highlighting the need for careful drug use.
Area of Science:
- Pharmacology
- Natural Products Chemistry
- Drug Metabolism
Background:
- Organic anion transporting polypeptide 1B1 (OATP1B1) is a crucial liver transporter for endogenous substances and drugs.
- Understanding OATP1B1 modulators from natural products is vital for predicting drug-drug and drug-food interactions.
- Natural products are widely used, necessitating investigation into their interactions with key drug transporters.
Purpose of the Study:
- To screen frequently used natural compounds for their potential to modulate OATP1B1 activity.
- To investigate the structure-activity relationships of natural compounds, particularly flavonoids, on OATP1B1.
- To explore the substrate-dependent effects of natural compounds on OATP1B1 function.
Main Methods:
- Utilized Chinese hamster ovary cells stably expressing OATP1B1 (CHO-OATP1B1) for high-throughput screening.
- Assessed OATP1B1-mediated transport of fluorescein methotrexate to identify inhibitors.
- Employed OATP1B1 substrates fluvastatin and rosuvastatin to investigate substrate-dependent interactions.
Main Results:
- Identified several flavonoids (quercetin, rutin) and triterpenoids (glycyrrhetinic acid, glycyrrhizic acid) as potent OATP1B1 inhibitors (IC50 < 16 µmol·L⁻¹).
- Found that flavonoid aglycones exhibited higher inhibitory activity than their glycosides, with sugar moiety influencing activity.
- Demonstrated that the impact of natural compounds on OATP1B1 function is substrate-dependent.
Conclusions:
- Natural compounds, including flavonoids and triterpenoids, can significantly inhibit OATP1B1, posing a risk for drug interactions.
- Structure-activity relationship analysis provides insights into designing safer natural product-based therapies.
- This research offers a basis for predicting and preventing OATP1B1-mediated drug-drug and drug-food interactions, guiding rational drug use.
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