In vitro inhibition of CYP3A4 by the multiherbal commercial product Sambucus Force and its main constituents Echinacea purpurea and Sambucus nigra

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.