Evaluation of in vitro Cytochrome P450 inhibition and hepatotoxicity potential of a herbal formula (Xiang Bei Yang Rong Tang) for treatment of cancer-related fatigue

Background: The modified Xiang Bei Yang Rong Tang (XBYRT) is a Chinese herbal medicine formulated to mitigate symptoms of cancer-related fatigue. XBYRT comprises of 15 herbal components which are commonly used in traditional Chinese medicine. Objectives: In this study, the in vitro inhibition of cytochrome P450 3A4 (CYP3A4) and cytochrome P450 2D6 (CYP2D6) activities, along with the in vitro liver cell toxicity were evaluated for XBYRT and the individual herbal components. Materials and Methods: CYP3A4 and CYP2D6 inhibitions were assayed using the Vivid^® CYP450 screening kits and liver cell toxicity in L-02 cells was analyzed using the 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) -2-(4-sulfophenyl)-2H-tetrazolium cell viability kit. The half maximal inhibitory concentrations (IC₅₀) for CYP450 inhibition and cell viability were determined using the non-linear regression from GraphPad Prism. Results: The IC₅₀ for CYP3A4 and CYP2D6 activities were 980 (942–1019) μg/ml and 1159 (1066–1261) μg/ml, respectively, for the XBYRT. The herbal components with the lowest IC₅₀ values for CYP3A4 activity were Radix Paeoniae Alba (144 μg/ml) and Rhizoma Cyperi (278 μg/ml), while herbal components with the lowest IC₅₀ values for CYP2D6 activity were Radix Codonopsis pilosulae (437 μg/ml) and Fructus Ligustri Lucidi (447 μg/ml). At the concentration of 256 μg/ml, XBYRT did not exhibit liver cell toxicity, with a 100% cell viability. Conclusion: The herbal components assessed did not demonstrate potent inhibitions of CYP3A4 and CYP2D6; however, precaution is recommended for breast cancer patients taking tamoxifen as the long-term impact of the herb-drug interaction is unclear. Further, in vivo and pharmacokinetic studies are required to ascertain the actual clinical significance of potential herb–drug interactions.