An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures
An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures
复制标题
DOI：
10.1016/s0944-7113(00)80044-6
复制
发表时间：
2000-07-01
期刊：
影响因子：
7.9
通讯作者：
Arnason, JT
中科院分区：
文献类型：
--
作者：
Budzinski, JW;Foster, BC;Arnason, JT
通过荧光微量滴定板测定，分析了 21 种商业乙醇草药提取物和酊剂以及 13 种相关纯植物化合物的连续稀释液的体外细胞色素 P450 3A4 (CYP3A4) 抑制能力。大约 75% 的商业产品和 50% 的纯化合物显示出对 CYP3A4 代谢物形成的显着抑制。对于每种草药产品和双关语：表现出剂量依赖性的化合物，抑制值用于使用线性回归生成中值抑制浓度 (IC50) 曲线。在商业提取物中，加拿大水螅（金丝瓜）、贯叶金丝桃（圣约翰草）和毛钩藤（猫爪草）的 IC50 值最低（< 1% 全强度），其次是紫锥菊根、红车轴草（野樱桃）、洋甘菊（洋甘菊）和光果甘草（甘草），其 IC50 值范围为全浓度的 1%-2%。在纯植物化合物中，Dillapiol、金丝桃素和柚皮素的 IC50 值最低，为 < 0.5 mM； dillapiol 是最有效的抑制剂，浓度是阳性 CYP3A4 抑制剂酮康唑的 23.3 倍。利用高通量筛选方法评估天然产物对 CYP3A4 的抑制作用，对于预测潜在草药-药物相互作用的可能性以及确定进一步深入分析的候选药物具有重要意义。
Serial dilutions of 21 commercial ethanolic herbal extracts and tinctures, and 13 related pure plant compounds have been analyzed for their in vitro cytochrome P450 3A4 (CYP3A4) inhibitory capability via a fluorometric microtitre plate assay. Roughly 75% of the commercial products and 50% of the pure compounds showed significant inhibition of CYP3A4 metabolite formation. For each herbal product and pun: compound exhibiting dose-dependency, the inhibition values were used to generate median inhibitory concentration (IC50) curves using linear regression. Among the commercial extracts, Hydrastis canadensis (goldenseal), Hypericum perforatum (St. John's wort), and Uncaria tomentosa (cat's claw) had the lowest IC50 values at < 1% full strength, followed by Echinacea angustifolia roots, Trifolium pratense (wild cherry), Matricaria chamomilla (chamomile), and Glycyrrhiza glabra (licorice), which had IC50 values ranging from 1%-2% of full strength. Dillapiol, hypericin, and naringenin had the lowest IC50 values among the pure plant compounds at < 0.5 mM; dillapiol was the most potent inhibitor at 23.3 times the concentration of the positive CYP3A4 inhibitor ketoconazole.Utilizing high-throughput screening methodologies for assessing CYP3A4 inhibition by natural products has important implications for predicting the likelihood of potential herbal-drug interactions, as well as determining candidates for further in-depth analyses.