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    Article

    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

    Ning Yi Yap1, Sheela Packiaraj David1, Huang Fang Zheng2, Quan Ming Tan2, Leona Yan Peng Quek2, Tze Kiat Tan2, Han Kiat Ho1, Alexandre Chan3,4★★ Corresponding author

    1. 1Department of Pharmacy, Faculty of Science, National University of Singapore.
    2. 2Singapore Thong Chai Medical Institution.
    3. 3Department of Pharmacy, National Cancer Centre Singapore, University of Singapore, Singapore.
    4. 4Department of Clinical Pharmacy Practice, University of California, Irvine, California, USA.

    CORRESPONDENCE

    Alexandre Chan

    Department of Pharmacy, National Cancer Centre Singapore, University of Singapore, Singapore.

    a.chan@uci.edu

    Received: 03-12-2020; Revised: 09-02-2021; Accepted: 18-03-2021.

    Volume 17, Issue 75 · pp. 630–635 · PUBLISHED 11 November 2021 · DOI: 10.4103/pm.pm_522_20

    View on Pharmacogn. Mag. original site ↗

    ABSTRACT

    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.

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      Yap, N. Y., David, S. P., Zheng, H. F., Tan, Q. M., Quek, L. Y. P., Tan, T. K., Ho, H. K., & Chan, A. (2021). 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. Pharmacognosy Magazine, 17(75), 630–635. https://doi.org/10.4103/pm.pm_522_20