Modulation of esterified drug metabolism by tanshinones from Salvia miltiorrhiza ("Danshen").
Modulation of esterified drug metabolism by tanshinones from Salvia miltiorrhiza ("Danshen").
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DOI：
10.1021/np300628a
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发表时间：
2013-01-25
影响因子：
5.1
通讯作者：
Potter PM
中科院分区：
文献类型：
--
作者：
Hatfield MJ;Tsurkan LG;Hyatt JL;Edwards CC;Lemoff A;Jeffries C;Yan B;Potter PM
丹参的根在传统的中药中被用来治疗许多疾病，包括心血管疾病、高血压和缺血性中风。复方丹参滴丸中丹参提取物正在美国进行临床试验，目前该材料的有效成分尚未确定。我们已经确定，由于丹参酮的存在，丹参根中含有有效的人类羧酸酯酶(CE)抑制剂。测定了NM范围内抑制肝脏和肠道CES的Ki值。研究了丹参酮类药物和丹参提取物对抗癌前体药物伊立替康(CPT-11)代谢的调节作用。我们的结果表明，与纯化合物和粗品孵育后，对人CES有明显的抑制作用，并且药物的水解度显著降低。因此，服用纯化的丹参酮或丹参提取物后，伊立替康的细胞毒性降低。结论是，当个人服用酯化药物时，应避免使用含有丹参酮的药物，并应警告患者这种材料可能发生的潜在药物-药物相互作用。
The roots of Salvia miltiorrhiza (“Danshen”) are used in traditional Chinese medicine for the treatment of numerous ailments including cardiovascular disease, hypertension, and ischemic stroke. Extracts of S. miltiorrhiza roots in formulation “Compound Danshen Dripping Pill” is undergoing clinical trials in the U.S. To date, the active components of this material have not been conclusively identified. We have determined that S. miltiorrhiza roots contain potent human carboxylesterase (CE) inhibitors, due to the presence of tanshinones. Ki values in the nM range were determined for inhibition of both the liver and intestinal CEs. As CEs hydrolyze clinically used drugs, the ability of tanshinones and S. miltiorrhiza root extracts to modulate the metabolism of the anticancer prodrug irinotecan (CPT-11) was assessed. Our results indicate that marked inhibition of human CEs occurs following incubation with both pure compounds and crude material, and that drug hydrolysis is significantly reduced. Consequently, a reduction in the cytotoxicity of irinotecan is observed following dosing with either purified tanshinones or S. miltiorrhiza root extracts. It is concluded that remedies containing tanshinones should be avoided when individuals are taking esterified agents, and that patients should be warned of the potential drug-drug interaction that may occur with this material.
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影响因子：
5.8
作者：
ELLMAN, GL;COURTNEY, KD;FEATHERSTONE, RM
通讯作者：
FEATHERSTONE, RM
影响因子：
7.3
作者：
Hyatt, JL;Stacy, V;Potter, PM
通讯作者：
Potter, PM
影响因子：
5.1
作者：
Djeridane, A.;Brunel, J. M.;Stocker, P.
通讯作者：
Stocker, P.
影响因子：
7.3
作者：
Hicks LD;Hyatt JL;Stoddard S;Tsurkan L;Edwards CC;Wadkins RM;Potter PM
通讯作者：
Potter PM
影响因子：
4.3
作者：
Lee, W. Y. W.;Chiu, L. C. M.;Yeung, J. H. K.
通讯作者：
Yeung, J. H. K.