Kavalactones yangonin and methysticin induce apoptosis in human hepatocytes (HepG2) in vitro

J. Tang, R. A. Dunlop, A. Rowe, K. J. Rodgers, Iqbal Ramzan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

While cases of severe kava hepatotoxicity have been reported, studies examining the toxicity of individual kavalactones are limited. The present study examined the in vitro hepatotoxicity of kavain, methysticin and yangonin on human hepatocytes (HepG2) and the possible mechanism(s) involved. Cytotoxicity was assessed using lactate dehydrogenase (LDH) and ethidium bromide (EB) assays. The mode of cell death was analysed with acridine orange/ethidium bromide dual staining with fluorescence microscopy. Glutathione oxidation was measured using the ortho-phthalaldehyde (OPT) fluorescence assay. Kavain had minimal cytotoxicity, methysticin showed moderate concentration-dependent toxicity and yangonin displayed marked toxicity with ∼40% reduction in viability in the EB assay. Acridine orange/ethidium bromide staining showed the predominant mode of cell death was apoptosis rather than necrosis. No significant changes were observed in glutathione levels, excluding this as the primary mechanism of cell death in this model. Further studies may elucidate the precise apoptotic pathways responsible and whether toxic kavalactone metabolites are involved.

Original languageEnglish
Pages (from-to)417-423
Number of pages7
JournalPhytotherapy Research
Volume25
Issue number3
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

Keywords

  • Apoptosis
  • Cytotoxicity
  • Hepatocyte
  • HepG2
  • Kavain
  • Kavalactone
  • Methysticin
  • Yangonin

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