Drugs on the Internet,Part V: Absinthe,Return of the Emerald Mask

Absinthe, a famous liquor of the 19th century, has become immensely popular with its return to legality and mass marketing and drug culture enhancement of its purported unique effects. The electronic world of the Internet has greatly expedited the extent and depth of societal knowledge about the allure of the green fairy, absinthe. An extensive number of websites exists, representing 22 categories of topics about or using the word absinthe. Recent research has dispelled many myths about absinthe and its effects, yet beliefs about its magical powers persist, thus maintaining its reputation as an extraordinary experience within a bohemian lifestyle.     

Metabolism of α-thujone in human hepatic preparations in vitro

1. This study aims to characterize the metabolism of α-thujone in human liver preparations in vitro and to identify the role of cytochrome P450 (CYP) and possibly other enzymes catalyzing α-thujone biotransformations.

2. With a liquid chromatography–mass spectrometry (LC-MS) method developed for measuring α-thujone and four potential metabolites, it was demonstrated that human liver microsomes produced two major (7- and 4-hydroxy-thujone) and two minor (2-hydroxy-thujone and carvacrol) metabolites. Glutathione and cysteine conjugates were detected in human liver homogenates, but not quantified. No glucuronide or sulphate conjugates were detected. Major hydroxylations accounted for more than 90% of the primary microsomal metabolism of α-thujone.

3. Screening of α-thujone metabolism with CYP recombinant enzymes indicated that CYP2A6 was principally responsible for the major 7- and 4-hydroxylation reactions, although CYP3A4 and CYP2B6 participated to a lesser extent and CYP3A4 and CYP2B6 catalyzed minor 2-hydroxylation. Based on the intrinsic efficiencies of different recombinant CYP enzymes and average abundances of these enzymes in human liver microsomes, CYP2A6 was calculated to be the most active enzyme in human liver microsomes, responsible for 70–80% of the metabolism on average.

4. Inhibition screening indicated that α-thujone inhibited both CYP2A6 and CYP2B6, with 50% inhibitory concentration values of 15.4 and 17.5 µM, respectively.

     

基于谱效关联分析筛选竹叶椒挥发油抗菌质量标志物

目的建立基于谱效关联分析的竹叶椒挥发油抗菌质量标志物(quality marker,Q-Marker)的研究方法,为其质量控制提供参考依据。方法采用气相色谱-质谱联用法(GC-MS)建立竹叶椒挥发油指纹图谱,并进行不同产地竹叶椒相似度评价、聚类分析和主成分分析;考察不同产地竹叶椒挥发油对大肠杆菌、金黄色葡萄球菌、红色毛癣菌及须鲜毛癣菌的作用;采用灰色关联分析法探究竹叶椒挥发油中的化学成分与抗菌活性的相关性,筛选Q-Marker。结果 10批不同产地竹叶椒挥发油相似度良好,相似度均大于0.97。不同产地竹叶椒挥发油对金黄色葡萄球菌、大肠杆菌、红色毛癣菌和须鲜毛癣菌均具有抑制作用。灰色关联分析表明,柠檬烯与金黄色葡萄球菌关联度值较高,芳樟醇、侧伯酮与大肠杆菌、红色毛癣菌和须鲜毛癣菌关联度值较高。结论柠檬烯、芳樟醇和侧柏醇可作为竹叶椒挥发油抗菌的潜在Q-Marker。     

Modulation of genotoxicity and DNA repair by plant monoterpenes camphor, eucalyptol and thujone in Escherichia coli and mammalian cells

The aim of this work was to examine the antigenotoxic potential of plant monoterpenes: camphor, eucalyptol and thujone in prokaryotic and eukaryotic cells and to elucidate their effect on DNA repair. We compared the effect of monoterpenes on spontaneous, UV- and 4NQO-induced mutagenesis in Escherichia coli K12 repair proficient, and MMR and NER deficient strains. Positive controls tannic acid and vanillin were included in bacterial tests. We also examined protective effect of monoterpenes against 4NQO-induced genotoxicity in Vero cell line by alkaline comet assay. The results obtained in repair proficient strain indicated antimutagenic potential of monoterpenes against UV- and 4NQO-induced mutagenesis, which was diminished with NER deficiency. Camphor and eucalyptol maintained UV-induced SOS response longer than in controls, while thujone decreased SOS response and reduced general protein synthesis and the growth rate. The three monoterpenes increased spontaneous and UV-induced recombination in recA730 and camphor additionally in recA⁺ cells. Incubation of 4NQO-pretreated Vero cells with monoterpenes resulted in significant reduction of tail moment. However, higher concentrations of monoterpenes induced DNA strand breaks. Obtained results indicate that by making a small amount of DNA lesions camphor, eucalyptol and thujone can stimulate error-free DNA repair processes and act as bioantimutagens.