Thujone, a widely debated volatile compound: What do we know about it?

Thujone is a volatile monoterpene ketone of plant origin which is produced by several plants that are frequently used for flavoring foods and beverages. The use of thujone and thujone-containing plant parts for human consumption is currently regulated by the European Parliament and Council and the European Medicines Agency. The best known neurotoxic effects are connected to the GABA-gated chloride channel, where alpha-thujone is a modulator roughly two to three times as potent as the beta isomer. Based primarily on in vitro experiments, genotoxicity and carcinogenic properties of thujones have also been detected in parallel with antimutagenic and immune-modulatory effects. Some of the controversial effects seem to be strongly dose-dependent. Data on antidiabetic and antimicrobial activities of thujones may show new ways to use them. This review also describes the main steps of the biosynthetic route of thujones and their occurrence in the plant kingdom. The accumulation of these compounds seems to be more abundant in some plant families (e.g. Asteraceae or Cupressaceae) than in others. Four species (Artemisia absinthium, Salvia officinalis, Tanacetum vulgare, Thuja occidentalis), characterised by a large intraspecific chemical variability, have been evaluated in detail from chemotaxonomical aspects. Experimental results show that the phenotypic manifestation and quantity of thujones in the essential oils depend on the plant organ and its developmental phase. Besides, weather conditions and growth habitat might also influence the ratios, as well as the possibly unique responses of the individual species. Unfortunately, comparison and an exact evaluation of the references is hampered by very diverse methods of treatment and analysis; sometimes reliability itself seems questionable. In order to optimise the safe use of thujone-containing preparations, it would be necessary to do further systematic studies from the plant biological, toxicological and pharmaco-kinetic points of view.