In vitro inhibition of UGT1A3, UGT1A4 by ursolic and oleanolic acid and drug-drug interaction risk prediction.
In vitro inhibition of UGT1A3, UGT1A4 by ursolic and oleanolic acid and drug-drug interaction risk prediction.
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熊果酸和齐墩果酸对 UGT1A3、UGT1A4 的体外抑制及药物相互作用风险预测。
DOI：
10.1080/00498254.2016.1234087
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发表时间：
2016
期刊：
影响因子：
1.8
通讯作者：
Xia Chunhua
中科院分区：
文献类型：
--
作者：
Xie Hongbo;Wu Jie;Liu Dan;Liu Mingyi;Zhang Hong;Huang Shibo;Xiong Yuqing;Xia Chunhua
1. 熊果酸（UA）和齐墩果酸（OA）可能具有与健康和疾病预防相关的重要活性。因此，我们研究了UA和OA对UDP-葡萄糖醛酸基转移酶(UGT)的活性，并使用三氟拉嗪作为探针底物来测试UGT1A4活性。重组UGT催化的4-甲基伞形酮(4-MU)葡萄糖醛酸化被用作其他UGT亚型的探针反应。2． UA和OA抑制UGT1A3和UGT1A4活性，但不抑制其他测试的UGT亚型。3． UA介导的UGT1A3催化4-MU-β-d-葡萄糖醛酸化的抑制是通过竞争性抑制实现的（IC500.391±0.013μM；Ki0.185±0.015μM）。 UA还竞争性抑制UGT1A4介导的三氟拉嗪-N-葡萄糖醛酸化(IC502.651±0.201μM；Ki1.334±0.146μM)。4． OA 对 UGT1A3 介导的 4-MU-β-d-葡萄糖醛酸化提供混合抑制 (IC500.336 ± 0.013 μM;Ki0.176 ± 0.007 μM) 并竞争性抑制 UGT1A4 介导的三氟拉嗪-N-葡萄糖醛酸化(IC505.468 ± 0.697 μM;Ki6.298 ± 0.891 μM).5. 将 OA 或 UA 与 UGT1A3 或 UGT1A4 底物的药物或产品共同给药可能会产生药物介导的副作用。
1. Ursolic acid (UA) and oleanolic acid (OA) may have important activity relevant to health and disease prevention. Thus, we studied the activity of UA and OA on UDP-glucuronosyltransferases (UGTs) and used trifluoperazine as a probe substrate to test UGT1A4 activity. Recombinant UGT-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used as a probe reaction for other UGT isoforms.2. UA and OA inhibited UGT1A3 and UGT1A4 activity but did not inhibit other tested UGT isoforms.3. UA-mediated inhibition of UGT1A3 catalyzed 4-MU-β-d-glucuronidation was via competitive inhibition (IC500.391 ± 0.013 μM;Ki0.185 ± 0.015 μM). UA also competitively inhibited UGT1A4-mediated trifluoperazine-N-glucuronidation (IC502.651 ± 0.201 μM;Ki1.334 ± 0.146 μM).4. OA offered mixed inhibition of UGT1A3-mediated 4-MU-β-d-glucuronidation (IC500.336 ± 0.013 μM;Ki0.176 ± 0.007 μM) and competitively inhibited UGT1A4-mediated trifluoperazine-N-glucuronidation (IC505.468 ± 0.697 μM;Ki6.298 ± 0.891 μM).5. Co-administering OA or UA with drugs or products that are substrates of UGT1A3 or UGT1A4 may produce drug-mediated side effects.