Chemical and in vitro toxicity analysis of a supercritical fluid extract of Kava kava (Piper methysticum)

Abstract

Ethnopharmacological relevance: Kava and kava extracts have shown great potential as a way to minimize anxiety-associated symptoms and to help alleviate pain. Hepatoxicity has been associated with the consumption of kava products. The chemical compounds, kavalactones (KL) and flavokavains (FK) have been implicated in kava's psychotropic and possible hepatotoxic properties.

Aim of the study: To investigate the kavalactone and flavokavain content and in vitro toxicity of KAVOA™, a supercritical carbon dioxide extraction (SFE) of kava.

Materials and methods: Kavalactone and flavokavain content of SFE kava and noble kava root were determined following extraction in acetone, cell culture media, and water using ultra high-performance liquid chromatography (UHPLC). Using water extractions of the kava products, the cell viability and toxicity on the human hepatocellular carcinoma cell line (HepG2) were determined using luminescent and fluorescent assays, respectively. The half maximal inhibitory concentration (IC₅₀) of the SFE kava and noble kava root, extracted in cell culture media, were determined utilizing a luminescent cell viability assay.

Results: Quantification of the KAVOA™, a SFE extract of kava and kava root showed similar profiles of kavalactone and flavokavain content. Water extracted SFE and root kava did not show a negative impact on cell viability and toxicity when compared to the vehicle control treated cells. IC₅₀ values were determined for the SFE kava and kava root extracted in cell culture media in respect to cell viability, 78.63 and 47.65 µg/mL, respectively.

Conclusions: KAVOA™, a supercritical carbon dioxide extract of kava displays a similar kavalactone profile to a noble variety of kava. In relation to total kavalactone content, KAVOA™ also has a lower content of the cytotoxic compound FKB. Aqueous extractions of KAVOA™ and noble kava root had no significant negative impact on cell viability and toxicity on HepG2 cells when compared to vehicle controlled treated cells. Results indicate KAVOA™ demonstrates a similar in vitro safety profile to that of noble kava root when experiments are normalized to kavalactone content.