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Updated: Jun 25, 2025

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Exploring Acute Liver Damage: Slimming Health Foods and CYP3A4 Induction.

Makiko Adachi1, Takeshi Kumagai2, Keiko Hosho3

  • 1Department of Pharmacy, Tottori University Hospital, Yonago 683-8504, Japan.

Yonago Acta Medica
|May 28, 2024
PubMed
Summary

Certain health foods, like Coleus forskohlii, can induce cytochrome P450 3A4 (CYP3A4) enzyme activity. This induction is linked to severe liver injury in patients taking multiple medications and supplements.

Keywords:
CYP3A4 inductionColeus forskohliiDILIacetaminophenslimming health foods

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Area of Science:

  • Pharmacology
  • Hepatology
  • Toxicology

Background:

  • Drug-drug and supplement-drug interactions can cause acute hepatitis in patients using multiple medications and health foods.
  • Investigating the role of health food and drug metabolism interactions is crucial for understanding severe liver injury.
  • Cytochrome P450 (CYP) enzymes play a key role in drug metabolism and potential toxicity.

Purpose of the Study:

  • To investigate the impact of slimming health food extracts on drug-metabolizing enzyme activity, specifically CYP.
  • To elucidate the molecular mechanisms underlying drug-induced liver injury.
  • To evaluate the hepatotoxicity of various health food components.

Main Methods:

  • Cytotoxicity assays using HepG2 cells were performed to assess cell viability upon exposure to health food extracts.
  • CYP3A4 induction was evaluated using reporter gene assays in engineered 3-1-10 cells.
  • A humanized CYP3A/pregnane X receptor (PXR) mouse model was used to confirm CYP3A4 induction in vivo.

Main Results:

  • Niacinamide and Gymnema sylvestre extracts demonstrated significant inhibition of HepG2 cell viability.
  • Dietary supplements A and Coleus forskohlii extract markedly induced CYP3A4 reporter activity.
  • Forskolin treatment in humanized mice led to a 3.9-fold increase in CYP3A4 mRNA expression.

Conclusions:

  • Coleus forskohlii extract exhibits potent transcriptional activation of the CYP3A4 gene.
  • Forskolin, a component related to Coleus forskohlii, induces CYP3A4 transcription in a relevant animal model.
  • CYP3A4 induction by Coleus forskohlii is implicated as a cause of hepatocellular injury, potentially via acetaminophen metabolism.