Abstract:
UNLABELLED:Abstract 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. OBJECTIVE:We investigated the interactions of these three compounds with the essential hepatic and renal SLC transporters. MATERIALS AND METHODS: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). RESULTS: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). DISCUSSION AND CONCLUSION: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.
journal_name
Pharm Bioljournal_title
Pharmaceutical biologyauthors
Li Z,Wang K,Zheng J,Cheung FS,Chan T,Zhu L,Zhou Fdoi
10.3109/13880209.2014.900809subject
Has Abstractpub_date
2014-12-01 00:00:00pages
1510-7issue
12eissn
1388-0209issn
1744-5116journal_volume
52pub_type
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