Thujone is an organic compound found in various plants, including wormwood (Artemisia absinthium), cedar, and juniper. This terpenoid is known for its medicinal properties but also for its potential toxicity when used in high doses. There are two main isomeric forms of thujone: α-thujone and β-thujone, each with slightly different characteristics. In cosmetics, thujone is used for its antimicrobial, aromatic, and stimulating properties.
Chemical Composition and Structure
It is a terpenoid with the chemical formula C10H16O. Its structure includes a cyclic ring with a ketone group (-C=O), making it a volatile and aromatic compound. The two main isomers, α-thujone and β-thujone, differ slightly in their spatial configuration.
Physical Properties
Thujone is a colorless or yellowish liquid, insoluble in water but soluble in organic solvents such as ethanol and essential oils. It has a distinctive, pungent odor reminiscent of absinthe. It is highly volatile and easily released into the air.
Production Process
Thujone is primarily extracted via steam distillation from the essential oils of plants containing it, such as wormwood and juniper. This process allows for the isolation of thujone along with other volatile components present in the plants.
Applications
- Medical: It is studied for its anti-inflammatory potential and as a possible antitumor agent.
- Cosmetics: Thujone is primarily used in perfumes and some personal care products due to its aromatic and stimulating properties. It is also present in certain formulations for its antimicrobial and preservative effects, enhancing the shelf life of products. However, due to its potential toxicity, its use is regulated and limited in some countries.
Health and Safety Considerations
Safety in Use
Thujone is known for its potential toxicity, especially when used in high concentrations. In cosmetics, its concentrations are carefully regulated to ensure product safety. It is considered an irritant for the skin and mucous membranes, so it is recommended for use in low concentrations and only in controlled formulations. Prolonged and unregulated use may lead to adverse reactions.
Allergic Reactions
Allergic reactions to thujone are possible, particularly in individuals sensitive to essential oils containing this compound. It is advisable to patch test products containing thujone before use.
Toxicity and Carcinogenicity
Thujone is considered toxic if ingested in large amounts and can cause seizures, confusion, and other neurological effects. Historically, it has been linked to the toxicity of absinthe, a liquor that contained it. However, when used in controlled concentrations in cosmetics, there is no evidence suggesting that thujone is carcinogenic. European and American regulations strictly limit the allowed concentrations of thujone in products.
Environmental Considerations
As a volatile component of essential oils, thujone can be released into the air during the production and use of products containing it. However, due to its natural origin and biodegradability, the environmental impact is generally low when used properly.
Regulatory Status
The use of thujone is regulated by various authorities, including the European Union and the FDA in the United States. In Europe, the thujone content in foods and cosmetic products is restricted to very low concentrations due to its toxicity.
References__________________________________________________________________________
Lee JY, Park H, Lim W, Song G. α,β-Thujone suppresses human placental choriocarcinoma cells via metabolic disruption. Reproduction. 2020 Jun;159(6):745-756. doi: 10.1530/REP-20-0018.
Abstract. α,β-Thujone is a natural terpenoid found in many medicinal herbs, such as Artemisia absinthium (wormwood), that exhibits antioxidant, anti-diabetic, and anti-tumorigenic effects. α,β-Thujone has numerous functions; it serves as a food ingredient, cosmetic additive, and medicinal remedy. Although the therapeutic properties of α,β-thujone were previously revealed, a comprehensive description of the mechanisms of its anti-cancer potential in choriocarcinoma is yet to be provided. To our knowledge, this study is the first to demonstrate that α,β-thujone attenuates JEG3 and JAR choriocarcinoma cells through a caspase-dependent intrinsic apoptotic pathway. Moreover, α,β-thujone was demonstrated to induce a global mitochondrial defect and ER stress in choriocarcinoma by causing mitochondrial depolarization, calcium overload, and metabolic alterations, thereby leading to energy deprivation, which eventually contributes to the increase in apoptosis of choriocarcinoma cells. Herein, we also revealed the synergistic anti-cancer activity of α,β-thujone via its sensitization effect on paclitaxel in choriocarcinoma cells. Altogether, our findings suggest that α,β-thujone is a novel, natural pharmacological compound that can be used to treat human placental choriocarcinoma.
Lachenmeier DW, Walch SG. The choice of thujone as drug for diabetes. Nat Prod Res. 2011 Dec;25(20):1890-2. doi: 10.1080/14786419.2011.622279.
Abstract. The use of thujone, a monoterpene ketone often present in sage (Salvia officinalis L.) or wormwood (Artemisia absinthium L.), for the treatment of diabetes mellitus was recently suggested in a study published in this journal. Evidence was based on the findings obtained in a diabetic rat model. After oral treatment with thujone (5 mg/kg bodyweight (bw)/day for 28 days), the cholesterol and triglyceride levels were significantly adjusted to normal levels when compared to diabetic, untreated rats. While these results sound promising and worthy of further investigation, the well-defined profile of the adverse properties of thujone demands a cautious interpretation of these results. The therapeutic margin of thujone appears to be small, as a dose-related incidence of seizures was noted in 2-year National Toxicology Program studies in rats and mice. The dose level in the diabetic rat study is also considerably higher than a daily intake that is acceptable for humans (0.1 mg/kg bw/day).
Siveen KS, Kuttan G. Thujone inhibits lung metastasis induced by B16F-10 melanoma cells in C57BL/6 mice. Can J Physiol Pharmacol. 2011 Oct;89(10):691-703. doi: 10.1139/y11-067.
Abstract. The antimetastatic potential of thujone, a naturally occurring monoterpene, was evaluated. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Administration of thujone (1 mg·(kg body weight)(-1)), prophylactically and simultaneously with tumor induction, inhibited tumor nodule formation in the lungs by 59.45% and 57.54%, respectively, with an increase in the survival rate (33.67% and 32.16%) of the metastatic tumor bearing animals. These results correlated with biochemical parameters such as lung collagen hydroxyproline, hexosamine and uronic acid contents, serum sialic acid and γ-glutamyl transpeptidase levels, and histopathological analysis. Treatment with thujone downregulated the production of proinflammatory cytokines such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and granulocyte-monocyte colony-stimulating factor. Thujone administration downregulated the expression of matrix metalloproteinase (MMP)-2, MMP-9, extracellular signal-regulated kinase (ERK)-1, ERK-2, and vascular endothelial growth factor (VEGF) and also upregulated the expression of nm-23, tissue inhibitor of metalloproteinase (TIMP)-1, and TIMP-2 in the lung tissue of metastasis-induced animals. Treatment with thujone inhibited the activity of MMP-2 and MMP-9 in gelatin zymographic analysis. Thujone treatment significantly inhibited the invasion of B16F-10 melanoma cells across the collagen matrix in a Boyden chamber. Thujone also inhibited the adhesion of tumor cells to collagen-coated microtire plate wells and the migration of B16F-10 melanoma cells across a polycarbonate filter in vitro. These results indicate that Thujone can inhibit the lung metastasis of B16F-10 cells through inhibition of tumor cell proliferation, adhesion, and invasion, as well as by regulating expression of MMPs, VEGF, ERK-1, ERK-2, TIMPs, nm23, and levels of proinflammatory cytokines and IL-2 in metastatic animals.
Pelkonen O, Abass K, Wiesner J. Thujone and thujone-containing herbal medicinal and botanical products: toxicological assessment. Regul Toxicol Pharmacol. 2013 Feb;65(1):100-7. doi: 10.1016/j.yrtph.2012.11.002. Epub 2012 Nov 28. PMID: 23201408.
Thujone 
