Potential Interaction of Pinocembrin with Drug Transporters and Hepatic Drug-Metabolizing Enzymes
Issued Date
2025-01-01
Resource Type
eISSN
14248247
Scopus ID
2-s2.0-85216130639
Journal Title
Pharmaceuticals
Volume
18
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Pharmaceuticals Vol.18 No.1 (2025)
Suggested Citation
Sangkapat S., Boonnop R., Pimta J., Chabang N., Nutho B., Jutabha P., Soodvilai S. Potential Interaction of Pinocembrin with Drug Transporters and Hepatic Drug-Metabolizing Enzymes. Pharmaceuticals Vol.18 No.1 (2025). doi:10.3390/ph18010042 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/103144
Title
Potential Interaction of Pinocembrin with Drug Transporters and Hepatic Drug-Metabolizing Enzymes
Corresponding Author(s)
Other Contributor(s)
Abstract
Background/Objectives: Pinocembrin is a promising drug candidate for treating ischemic stroke. The interaction of pinocembrin with drug transporters and drug-metabolizing enzymes is not fully revealed. The present study aims to evaluate the interaction potential of pinocembrin with cytochrome P450 (CYP450: CYP2B6, CYP2C9, and CYP2C19) and drug transporters including organic anion transporters (OAT1 and OAT3), organic cation transporters (OCT1 and OCT2), multidrug and toxin extrusion (MATE1 and MATE2, P-glycoprotein (P-gp), and breast cancer resistance protein (BCRP). Methods: The interactions of pinocembrin on drug transporters were determined in the Madin–Darby canine kidney (MDCK) cells overexpressing human (h)OAT1 or hOAT3 and in the Chinese hamster ovary (CHO-K1) cells overexpressing hOCT1, hOCT2, hMATE1, or hMATE2. The interactions of pinocembrin with BCRP and P-glycoprotein were determined in Caco-2 cells. The CYP450 enzyme inhibitory activity was assessed by a cell-free CYP450 screening assay. Results: Pinocembrin effectively inhibited the function of OAT1 and OAT3 with a half-inhibitory concentration (IC50) and inhibitory constant (Ki) of ∼2 μM. In addition, it attenuated the toxicity of tenofovir, a substrate of hOAT1, in cells overexpressing hOAT1. Based on the kinetic study and molecular docking, pinocembrin inhibited OAT1 and OAT3 via a competitive inhibition. In contrast to hOAT1 and hOAT3, pinocembrin did not significantly inhibit the function of OCT1, OCT2, MATE1, MATE2, BCRP, and P-glycoprotein. In addition, pinocembrin potently inhibited the activity of CYP2C19, whereas it exhibited low inhibitory potency on CYP2B6 and CYP2C9. Conclusions: The present study reveals the potential drug interaction of pinocembrin on OAT1, OAT3, and CYP2C19. Co-administration with pinocembrin might affect OAT1-, OAT3-, and CYP2C19-mediated drug pharmacokinetic profiles.