Disease relevance of THUJONE

• The ingredient causing absinthe's toxicity is believed to be thujone [1].

High impact information on THUJONE

• Wormwood (Artemisia absinthium) was the most significant constituent because it contributed thujone [2].
• Second, a strain of Drosophila specifically resistant to chloride channel blockers is also tolerant to alpha-thujone [3].
• Four observations establish that alpha-thujone is a modulator of the gamma-aminobutyric acid (GABA) type A receptor [3].
• Third, alpha-thujone is a competitive inhibitor of [(3)H]ethynylbicycloorthobenzoate binding to mouse brain membranes [3].
• Alpha-thujone (1alpha) and beta-thujone (1beta) were used to investigate the mechanism of hydrocarbon hydroxylation by cytochromes P-450(cam) (CYP101) and P-450(BM3) (CYP102) [4].

Chemical compound and disease context of THUJONE

• The toxicity of each oil appeared to be related to the presence of terpenic ketones, camphor in sage commercial oil, camphor and thujone in sage Dalmatian oil, thujone in thuja and cedar oils, and pinocamphone in hyssop oil [5].

Biological context of THUJONE

• Seasonal variations in the oil compositions were not considerable except for the starting phase (May 25, 1995), when the content of carvone was lower and the content of alpha-thujone and sesquiterpenes higher [6].
• Terpenoid biotransformation in mammals. V. Metabolism of (+)-citronellal, (+-)-7-hydroxycitronellal, citral, (-)-perillaldehyde, (-)-myrtenal, cuminaldehyde, thujone, and (+-)-carvone in rabbits [7].

Anatomical context of THUJONE

• We report here unexpected site specificity and species differences in the metabolism of the thujone diastereomers in mouse, rat, and human liver microsomes and human recombinant P450 (P450 3A4), in orally treated mice and rats, and in Drosophila melanogaster [8].
• Radioligand receptor binding assays employing membrane preparations from rat brains containing CB1 cannabinoid receptors, and human tonsils containing CB2 receptors, demonstrated that thujone displaced [3H]CP55940, a cannabinoid agonist, only at concentrations above 10 microM [9].

Associations of THUJONE with other chemical compounds

• The major volatile constituents of the extract by SPSE were 1,8-cineole (8.12 ppm), artemisia acetate (4.22 ppm), alpha-thujone (3.20 ppm), beta-caryophyllene (2.39 ppm), bornyl acetate (2.05 ppm), borneol (1.80 ppm), and trans-beta-farnesene (1. 78 ppm) [10].
• The quantitatively most important components of yarrow were sabinene, beta-pinene, 1,8-cineole, artemisia ketone, linalool, alpha-thujone, beta-thujone, camphor, borneol, fenchyl acetate, bornyl acetate, (E)-beta-caryophyllene, germacrene D, caryophyllene oxide, beta-bisabolol, delta-cadinol, chamazulene etc [11].

Gene context of THUJONE

• HPLC analysis of oil of wormwood revealed that only the fractions having mobility close to thujone displaced [3H]CP55940 from the CB1 cannabinoid receptor [9].
• Thus, alpha-thujone in absinthe and herbal medicines is a rapid-acting and readily detoxified modulator of the GABA-gated chloride channel [3].
• Alpha-thujone reduces 5-HT3 receptor activity by an effect on the agonist-reduced desensitization [12].
• The thujone diastereomers are rapidly metabolized convulsants acting as noncompetitive blockers of the gamma-aminobutyric acid-gated chloride channel [13].

References