{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:46:59Z","timestamp":1792802819739,"version":"4.5.0"},"reference-count":32,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mahidol University","award":["BRF1-048\/2565"],"award-info":[{"award-number":["BRF1-048\/2565"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>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\u2013Darby 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 \u223c2 \u03bcM. 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.<\/jats:p>","DOI":"10.3390\/ph18010042","type":"journal-article","created":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T11:24:19Z","timestamp":1735730659000},"page":"42","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Potential Interaction of Pinocembrin with Drug Transporters and Hepatic Drug-Metabolizing Enzymes"],"prefix":"10.3390","volume":"18","author":[{"given":"Sirima","family":"Sangkapat","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology, College of Pharmacy, Rangsit University, Pathumthani 12000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rattiporn","family":"Boonnop","sequence":"additional","affiliation":[{"name":"Research Center of Transport Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeerawat","family":"Pimta","sequence":"additional","affiliation":[{"name":"Research Center of Transport Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Napason","family":"Chabang","sequence":"additional","affiliation":[{"name":"School of Bioinnovation and Bio-based Product Intelligence (SCIN), Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bodee","family":"Nutho","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8475-8921","authenticated-orcid":false,"given":"Promsuk","family":"Jutabha","sequence":"additional","affiliation":[{"name":"Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bang Phli, Samut Prakan 10540, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunhapas","family":"Soodvilai","sequence":"additional","affiliation":[{"name":"Research Center of Transport Protein for Medical Innovation, Department of Physiology, Faculty of Science, Mahidol University, Ratchathewi, Bangkok 10400, Thailand"},{"name":"Excellent Center for Drug Discovery, Mahidol University, Ratchathewi, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Elbatreek, M.H., Mahdi, I., Ouchari, W., Mahmoud, M.F., and Sobeh, M. 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