Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice.
Curcumin inhibits the activity of ABCG2/BCRP1, a multidrug resistance-linked ABC drug transporter in mice.
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DOI：
10.1007/s11095-008-9735-8
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发表时间：
2009-02
影响因子：
3.7
通讯作者：
Ambudkar, Suresh V.
中科院分区：
文献类型：
--
作者：
Shukla, Suneet;Zaher, Hani;Hartz, Anika;Bauer, Bjorn;Ware, Joseph A.;Ambudkar, Suresh V.
评估姜黄素作为多药耐药ATP结合盒（ABC）药物转运体ABCG2抑制剂的体内疗效。用[125I]-碘arylazidoprazosin进行光亲和标记，表征小鼠ABCG2的底物磺胺嘧啶与人ABCG2的相互作用。此外，我们还观察了姜黄素对大鼠脑毛细血管中ABCG2的抑制作用。此外，还测定了姜黄素对口服给药磺胺氮嗪在野生型和abcg2-/-小鼠体内吸收的影响。柳氮磺胺吡啶在人ABCG2的药物-底物位点相互作用。在离体实验中，姜黄素以纳摩尔浓度在大鼠血脑屏障处抑制ABCG2活性。通过对野生型和abcg2-/-小鼠的研究，我们发现口服姜黄素通过选择性抑制abcg2的功能，提高了Cmax和磺胺氮嘧啶的相对生物利用度。本研究验证了我们之前在人ABCG2的体外实验结果（Mol. Cancer Ther. 2006; 5:95 -2006），并首次提供了姜黄素抑制ABCG2介导的磺胺嘧啶在小鼠体内外排的体内证据。基于这些研究，我们提出，当药物吸收和/或组织分布的限速步骤受到ABCG2的影响时，无毒浓度的姜黄素可以用来增强药物暴露。
To evaluate the in vivo efficacy of curcumin as an inhibitor of the multidrug-resistance-linked ATP Binding Cassette (ABC) drug transporter, ABCG2. Photoaffinity labeling with [125I]-iodoarylazidoprazosin was used to characterize the interaction of sulfasalazine, a substrate of the mouse ABCG2, with human ABCG2. In addition, the inhibitory effect of curcumin on ABCG2 was evaluated in brain capillaries from rats. Furthermore, the effect of curcumin on absorption of orally administered sulfasalazine in wild-type and abcg2-/- mice was also determined. Sulfasalazine interacted at the drug-substrate site(s) of human ABCG2. Curcumin inhibited ABCG2 activity at nanomolar concentrations at the rat blood-brain barrier in the ex vivo assay. Based on studies in wild type and abcg2-/- mice, we observed that oral curcumin increased Cmax and relative bioavailability of sulfasalazine by selectively inhibiting ABCG2 function. This study validates our previous in vitro results with human ABCG2 (Mol. Cancer Ther. 2006; 5:1995-2006) and provides the first in vivo evidence for the inhibition by curcumin of ABCG2-mediated efflux of sulfasalazine in mice. Based on these studies, we propose that non-toxic concentrations of curcumin may be used to enhance drug exposure when the rate-limiting step of drug absorption and/or tissue distribution is impacted by ABCG2.
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影响因子：
4.3
作者：
Limtrakul, Pornngarm;Chearwae, Wanida;Ambudkar, Suresh V.
通讯作者：
Ambudkar, Suresh V.
影响因子：
3.6
作者：
Bauer, Bjoern;Hartz, Anika M. S.;Potschka, Heidrun
通讯作者：
Potschka, Heidrun
影响因子：
3.6
作者：
Choi, Hyunsung;Chun, Yang-Sook;Park, Jong-Wan
通讯作者：
Park, Jong-Wan
影响因子：
10.3
作者：
Jonker, JW;Smit, JW;Schinkel, AH
通讯作者：
Schinkel, AH
影响因子：
5.8
作者：
Chearwae, W;Anuchapreeda, S;Limtrakul, P
通讯作者：
Limtrakul, P