Interactions of the active components ofPunica granatum(pomegranate) with the essential renal and hepatic human Solute Carrier transporters
| Autor: | Ting Chan, Ling Zhu, Florence S.G. Cheung, Fanfan Zhou, Ke Wang, Jian Zheng, Zhen Li |
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| Rok vydání: | 2014 |
| Předmět: |
Drug
Organic Cation Transport Proteins media_common.quotation_subject Herb-Drug Interactions Active components Organic Anion Transporters Pharmaceutical Science Context (language use) Kidney Inhibitory Concentration 50 Gallic Acid Drug Discovery Humans Oleanolic Acid media_common Lythraceae Pharmacology Dose-Response Relationship Drug biology Chemistry Transporter General Medicine biology.organism_classification Triterpenes Solute carrier family HEK293 Cells Liver Complementary and alternative medicine Biochemistry Membrane protein Punica Molecular Medicine |
| Zdroj: | Pharmaceutical Biology. 52:1510-1517 |
| ISSN: | 1744-5116 1388-0209 |
| DOI: | 10.3109/13880209.2014.900809 |
| Popis: | Context: Solute carrier transporters (SLCs) are membrane proteins responsible for cellular influx of various substances including many pharmaceutical agents; therefore, they largely impact on drug disposition and elimination in body. Punica granatum Linnaeus (Lythraceae), pomegranate, is a fruit with antidiabetic potential. Oleanolic acid (OA), ursolic acid (UA), and gallic acid (GA) are the major bioactive components of pomegranate. Co-administration of these compounds with other drugs could result in altered drug pharmacokinetics, possibly due to competing for transporter proteins.We investigated the interactions of these three compounds with the essential hepatic and renal SLC transporters.Uptake of radiolabeled transporter model substrates was assessed in HEK293 cells over-expressing SLC transporters including the organic anion transporters (OATs), organic anion transporting polypeptides (OATPs) and organic cation transporters (OCTs), in the presence or absence of 10.0 µM UA, OA, or GA. Their IC50 values on specific SLC transporters were also evaluated using varying concentrations of the particular compound (ranging from 0.10 nM to 80.0 µM).Our results demonstrated UA could significantly inhibit OAT3 and OATP2B1 uptake (IC50: 18.9 ± 8.20 µM and 11.0 ± 5.00 µM, respectively) and GA has a pronounced inhibitory effect on OATP1B3 uptake (IC50: 1.60 ± 0.60 μM).Our study reports the interactions of OA, UA, and GA with the essential SLC transporters. This information may contribute to elucidating the drug-drug/herb interactions involved with these three compounds and form the basis of therapeutic optimization when drugs are co-administered. |
| Databáze: | OpenAIRE |
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