Thujone Isomer: Chemistry, Natural Occurrence, Neuropharmacology and Toxicological Assessment – A Critical Review

Abstract

Thujone is a naturally occurring bicyclic monoterpene ketone found in several aromatic plants, particularly species belonging to the genera Artemisia, Salvia and Thuja. Its chemical diversity, biological activities and potential toxicological effects have attracted considerable scientific interest, particularly because of its historical association with absinthe and its neuroactive properties. This review critically examines current knowledge of thujone, focusing on its chemical structure, stereochemistry, natural occurrence, biosynthesis, extraction, analytical characterisation, neuropharmacological activities and toxicological significance. Particular attention is given to the structural differences between α- and β-thujone and their implications for biological activity and safety assessment. The review also discusses the influence of botanical sources, chemotypic variation, geographical and environmental factors, and extraction procedures on the composition of thujone-containing essential oils. Available experimental evidence indicates that thujone can modulate gamma-aminobutyric acid type A (GABA(A)) receptor activity, providing a mechanistic basis for its neuroexcitatory and convulsant effects at elevated exposure levels. Furthermore, differences in metabolic transformation and detoxification may contribute to variations in its toxicological profile. Computational approaches, including SwissADME and ProTox, are considered as complementary tools for investigating physicochemical, pharmacokinetic and toxicity-related properties, while recognising their predictive limitations. Overall, the review highlights the importance of stereoisomer-specific chemical analysis, improved understanding of biosynthetic pathways, standardised analytical procedures and integrated experimental and computational investigations. These approaches are essential for advancing the scientific understanding of thujone and supporting the quality control and safety assessment of thujone-containing botanical products.

Abstract as supplied by the indexing source. © the authors / publisher.