Interaction of five anthraquinones from rhubarb with human organic anion transporter 1 (SLC22A6) and 3 (SLC22A8) and drug-drug interaction in rats

作者 Ma, Liping; Zhao, Lei; Hu, Haihong; Qin, Yahong; Bian, Yicong; Jiang, Huidi; Zhou, Hui; Yu, Lushan; Zeng, Su

期刊 JOURNAL OF ETHNOPHARMACOLOGY , MAY 14 2014,3:153

DOI 10.1016/j.jep.2014.03.055 PubMed 24685584

摘要 Ethnopharmacological relevance: Rhubarb is a well-known traditional Chinese medicine and has been used in China for thousands of years. Anthraquinone derivatives including rhein, emodin, aloe-emodin, chrysophanol and physcion are the important components in rhubarb.Materials and methods: Here we studied the interaction of five anthraquinone derivatives with human renal organic anion transporter 1 (hOAT1) and hOAT3 stably expressed in cells, and interaction of rhein or rhubarb extract (RE) with furosemide (FS, substrate of OATs) in rats.Results: Uptake of 6-carboxyl fluorescein via hOAT1 and fluorescein via hOAT3 were markedly inhibited by rhein, emodin and aloe-emodin, and slightly inhibited by chrysophanol and physcion. The estimated IC50 values for rhein, emodin, aloe-emodin and probenecid (typical inhibitor of hOAT1 and hOAT3) were 0.23, 0.61, 2.29 and 18.34 mu M for hOAT1, and 0.08, 1.22, 537 and 5.83 mu M for hOAT3, respectively. Furthermore, the data from the cellular accumulation assay indicated that these five compounds were not substrates of hOAT1 or hOAT3. Pharmacokinetic interaction between rhein and FS in rats showed that area under the curve (AUC(o-t)) for FS was increased by 65% when coadministrated with rhein. RE was also used to interact with FS in rats and results showed that AUC(o-t) of FS was increased by 32% and by 52% when coadministrated with single-dose or multiple-dose of RE, respectively.Conclusions: These findings suggested that five anthraquinones inhibited hOAT1 and hOAT3, but these compounds were not transported by hOAT1 or hOAT3. Furthermore, rhein or RE, might cause drug-drug interaction when coadministrated with substrates of OAT1 or OAT3 in vivo. (c) 2014 Elsevier Ireland Ltd. All rights reserved.