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Metabolism-mediated drug interaction potential of HS-23, a new herbal drug for the treatment of sepsis in human hepatocytes and liver microsomes

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Abstract

HS-23, an extract of the dried flower buds of Lonicera japonica, is a new botanical drug currently being evaluated in a phase I clinical study in Korea for the treatment of sepsis. The in vitro induction and inhibition potentials of HS-23 on the drug-metabolizing enzymes using human hepatocytes and liver microsomes were assessed to evaluate herb–drug interaction according to botanical drug guideline and drug interaction guidance of FDA. HS-23 slightly inhibited CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4 enzyme activities in human liver microsomes with IC50 values of 80.6, 160.7, 169.5, 85.4, and 76.6 μg/mL, respectively. HS-23 showed negligible inhibition of CYP1A2, CYP2C8, CYP2D6, UGT1A1, UGT1A4, UGT1A9, and UGT2B7 activities in human liver microsomes. Based on these results, HS-23 may not inhibit the metabolism of CYP2A6, CYP2B6, CYP2C9, CYP2C19, and CYP3A4-catalyzed drugs in humans. HS-23 did not affect the mRNA expression of CYP1A2, CYP2B6, and CYP3A4 after 48 h treatment at three concentrations (0.5, 5, and 50 μg/mL) in three independent human hepatocytes, indicating that HS-23 has no effect on herb–drug interactions that up- or down-regulate CYP1A2, CYP2B6, and CYP3A4. These results indicate that the administration of HS-23 in human may not cause clinically relevant inhibition and induction of these cytochrome P450 (CYP) and UDP-glucuronosyltransferase (UGT) enzymes and HS-23 may be promising therapeutic agent for treatment of sepsis.

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Acknowledgments

This study was supported by a Grant (A121826) from health technology from Health Technology Development Program through the Ministry of Health and Welfare of Korea to Huons and The Catholic University of Korea, 2012 (M-2012-B0002-00024).

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The authors declared no conflict of interest.

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Authors and Affiliations

  1. College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi-do, 420-743, Republic of Korea

    Hyeon-Uk Jeong, Ji Young Lee, Soon-Sang Kwon, Ju Hyun Kim, Yong-Yeon Cho & Hye Suk Lee

  2. Department of New Drug Development, Huons Co., Ltd., Ansan, 426-791, Republic of Korea

    Young-Mok Kim & Sung-Woon Hong

  3. Botanical Drug Research Team, Huons Co., Ltd., Ansan, 426-791, Republic of Korea

    Sung Hum Yeon

  4. School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea

    Sun-Mee Lee

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  1. Hyeon-Uk Jeong
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Jeong, HU., Lee, J.Y., Kwon, SS. et al. Metabolism-mediated drug interaction potential of HS-23, a new herbal drug for the treatment of sepsis in human hepatocytes and liver microsomes. Arch. Pharm. Res. 38, 171–177 (2015). https://doi.org/10.1007/s12272-014-0453-y

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