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<p>Kava, the root of <i>Piper methysticum</i> – plants dominantly cultivated in the South Pacific Islands, is traditionally consumed in the form of an aqueous suspension for its stress-reducing benefits. Beyond its traditional use, kava has demonstrated anticancer, anti-inflammatory, anxiolytic and other potentials. These effects are largely attributed to its major components, termed kavalactones. However, clinical findings of purported hepatotoxic risk have raised its safety concerns with a few causes hypothesized, including the potential of drug-herb interactions due to kavalactone perturbation of cytochrome P450 enzymes. In order to rigorously evaluate kava in the preclinical and clinical settings for its potential benefits and risks in future studies, a critical assessment of the possible contributing factors and mechanisms behind its purported hepatotoxic risk is essential. This review examines the current data on kava and kavalactones to modulate cytochrome P450 enzymes, including biochemical, cell-based, animal, and clinical data, and assess their potential contribution to kava’s hepatotoxic risk due to drug-herb interactions.</p><p></p>

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The potential of major kavalactones in modulating cytochrome P450 enzymes

  • 期刊论文

  • 发表日期：

    2025年10月21日

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  • Allison Lynch,
  • Yifan Wang,
  • Gujie Xu,
  • Ananya Balasubramanian,
  • Chengguo Xing

摘要

Kava, the root of Piper methysticum – plants dominantly cultivated in the South Pacific Islands, is traditionally consumed in the form of an aqueous suspension for its stress-reducing benefits. Beyond its traditional use, kava has demonstrated anticancer, anti-inflammatory, anxiolytic and other potentials. These effects are largely attributed to its major components, termed kavalactones. However, clinical findings of purported hepatotoxic risk have raised its safety concerns with a few causes hypothesized, including the potential of drug-herb interactions due to kavalactone perturbation of cytochrome P450 enzymes. In order to rigorously evaluate kava in the preclinical and clinical settings for its potential benefits and risks in future studies, a critical assessment of the possible contributing factors and mechanisms behind its purported hepatotoxic risk is essential. This review examines the current data on kava and kavalactones to modulate cytochrome P450 enzymes, including biochemical, cell-based, animal, and clinical data, and assess their potential contribution to kava’s hepatotoxic risk due to drug-herb interactions.