Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay.
Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay.
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DOI：
10.3390/molecules16097344
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发表时间：
2011-08-29
期刊：
影响因子：
--
通讯作者：
Mohamed Z
中科院分区：
文献类型：
--
作者：
Kong WM;Chik Z;Ramachandra M;Subramaniam U;Aziddin RE;Mohamed Z
帽柱木提取物已被广泛用作鸦片替代品，主要是由于其具有类似吗啡的药理作用。本研究使用改良的 Crespi 方法研究了大花木生物碱提取物 (MSE) 对人重组细胞色素 P450 (CYP) 酶活性的影响。与液相色谱-质谱法相比，该方法已被证明是一种快速且经济有效的 CYP 抑制研究方法。结果表明，MSE对CYP3A4和CYP2D6具有最强的抑制作用，表观半数抑制浓度(IC50)值分别为0.78 µg/mL和0.636 µg/mL。此外，对 CYP1A2 观察到中度抑制，IC50 为 39 µg/mL，对 CYP2C19 检测到弱抑制。然而，无法确定 CYP2C19 的 IC50，因为抑制率 <50%。 MSE 处理的 CYP2D6 抑制测定发现竞争性抑制，而使用 CYP3A4、CYP1A2 和 CYP2C19 的抑制测定则显示非竞争性抑制。奎尼丁（CYP2D6）、酮康唑（CYP3A4）、反苯环丙明（CYP2C19）和呋拉茶碱（CYP1A2）在整个实验中用作阳性对照。这项研究表明，如果与 CYP3A4、CYP2D6 和 CYP1A2 底物药物同时服用，MSE 可能会导致草药与药物之间的相互作用。
The extract from Mitragyna speciosa has been widely used as an opium substitute, mainly due to its morphine-like pharmacological effects. This study investigated the effects of M. speciosa alkaloid extract (MSE) on human recombinant cytochrome P450 (CYP) enzyme activities using a modified Crespi method. As compared with the liquid chromatography-mass spectrometry method, this method has shown to be a fast and cost-effective way to perform CYP inhibition studies. The results indicated that MSE has the most potent inhibitory effect on CYP3A4 and CYP2D6, with apparent half-maximal inhibitory concentration (IC50) values of 0.78 µg/mL and 0.636 µg/mL, respectively. In addition, moderate inhibition was observed for CYP1A2, with an IC50 of 39 µg/mL, and weak inhibition was detected for CYP2C19. The IC50 of CYP2C19 could not be determined, however, because inhibition was <50%. Competitive inhibition was found for the MSE-treated CYP2D6 inhibition assay, whereas non-competitive inhibition was shown in inhibition assays using CYP3A4, CYP1A2 and CYP2C19. Quinidine (CYP2D6), ketoconazole (CYP3A4), tranylcypromine (CYP2C19) and furafylline (CYP1A2) were used as positive controls throughout the experiments. This study shows that MSE may contribute to an herb-drug interaction if administered concomitantly with drugs that are substrates for CYP3A4, CYP2D6 and CYP1A2.
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影响因子：
5.4
作者：
Chittrakarn, Somsmorn;Sawangjaroen, Kitja;Kempradub, Niwat
通讯作者：
Kempradub, Niwat
影响因子：
2.9
作者：
Crespi, CL;Miller, VP;Penman, BW
通讯作者：
Penman, BW
DOI：
10.3390/molecules15010432
发表时间：
2010-01-20
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Azizi J;Ismail S;Mordi MN;Ramanathan S;Said MI;Mansor SM
通讯作者：
Mansor SM
影响因子：
3.3
作者：
Babu, Kavita M.;McCurdy, Christopher R.;Boyer, Edward W.
通讯作者：
Boyer, Edward W.
影响因子：
3.9
作者：
Ito, K;Ogihara, K;Itoh, T
通讯作者：
Itoh, T