Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Norway.
Phytother Res. 2012 Nov;26(11):1606-13. doi: 10.1002/ptr.4619. Epub 2012 Feb 8.
The multiherbal product Sambucus Force contains Echinacea purpurea and Sambucus nigra as its main constituents. The aims of this study were to evaluate Sambucus Force's inhibition potential and inhibition mechanisms towards CYP3A4, and to evaluate the inhibitory co-contribution of E. purpurea and S. nigra. Metabolic studies were performed with recombinant human CYP3A4, with testosterone as substrate. Sambucus Force inhibited CYP3A4 activity with a mean (95% confidence interval) half maximal inhibitory concentration (IC(50) ) value of 1192 (1091-1302) µg/mL. The inhibitory potency seems exclusively to be exerted by E. purpurea, implicating an insignificant inhibition by S. nigra. The inhibition by E. purpurea as a single herb was in agreement with mechanism-based inhibition with heterotropic positive cooperative effects. Echinacea purpurea acted differently in the multiherbal product, which showed a dual inhibition profile with both an uncompetitive (substrate-dependent) inhibition and a time-dependent (substrate-independent) inhibitory mechanism. These mechanistic differences are suggested to be caused by herb-herb interactions in the multiherbal product. The CYP3A4 inhibition of Sambucus Force in vitro is considered relatively weak, but recommended high herbal dosages might enhance the potential for clinical interactions.
该多草药产品桑菊力含有紫锥菊和黑接骨木作为其主要成分。本研究旨在评估桑菊力对 CYP3A4 的抑制潜力及其抑制机制，并评估紫锥菊和黑接骨木的抑制协同作用。代谢研究用人重组 CYP3A4 进行，以睾酮为底物。桑菊力对 CYP3A4 活性的抑制作用的半数最大抑制浓度（IC50）值为 1192（1091-1302）μg/ml。抑制作用似乎完全是由紫锥菊发挥的，黑接骨木的抑制作用微不足道。作为单一草药，紫锥菊的抑制作用与机制基础抑制作用一致，具有异质正协同效应。紫锥菊在多草药产品中的作用方式不同，表现出非竞争（底物依赖）抑制和时间依赖性（底物非依赖）抑制的双重抑制模式。这些机制差异可能是由于多草药产品中的草药-草药相互作用所致。桑菊力在体外对 CYP3A4 的抑制作用被认为相对较弱，但推荐的高草药剂量可能会增强潜在的临床相互作用。
