Budzinski J W, Foster B C, Vandenhoek S, Arnason J T
Ottawa-Carleton Institute of Biology, University of Ottawa, Ontario, Canada.
Phytomedicine. 2000 Jul;7(4):273-82. doi: 10.1016/S0944-7113(00)80044-6.
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 pure 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.
通过荧光微量滴定板分析法，对21种市售乙醇草药提取物和酊剂以及13种相关纯植物化合物的系列稀释液进行了体外细胞色素P450 3A4（CYP3A4）抑制能力分析。大约75%的市售产品和50%的纯化合物对CYP3A4代谢物形成表现出显著抑制作用。对于每种呈现剂量依赖性的草药产品和纯化合物，使用线性回归将抑制值用于生成半数抑制浓度（IC50）曲线。在市售提取物中，加拿大升麻（白毛茛）、贯叶连翘（圣约翰草）和绒毛钩藤（猫爪草）在全强度<1%时IC50值最低，其次是狭叶松果菊根、红车轴草（野樱桃）、母菊（洋甘菊）和光果甘草（甘草），其IC50值范围为全强度的1%-2%。莳萝脑、金丝桃素和柚皮素在纯植物化合物中IC50值最低，<0.5 mM；莳萝脑是最有效的抑制剂，其浓度为阳性CYP3A4抑制剂酮康唑浓度的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物具有重要意义。
