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The genus Phagnalon Cass. (Asteraceae) is composed of widely distributed species and most of them, due to the medicinal properties they possess, are widely used in folk medicine but also as spices in the culinary field. The polar and non-polar extracts, as well as the complex mixtures of their essential oils, from several Phagnalon species and ssp., have shown antibiotic, antiviral, cytotoxic, and several other biological properties. In this work, the chemical composition and the antimicrobial, cytotoxic, and antioxidant properties of the Jordan accession of Phagnalon sinaicum Bornm. & Kneuck. essential oil (EO), an extremely rare plant that grows in ravines in the Middle East, were investigated. The EO, analyzed by GC-MS, was found to be rich in terpenoid compounds, and, in particular, in oxygenated monoterpenes, with the main compound being artemisia ketone (22.3%), followed by α-thujone (17.7%), and santolin alcohol (14.8%). The EO had good antimicrobial activity, especially against Escherichia coli Gram-negative bacterium (3 mg/mL MIC values) and was also effective in counteracting in vitro biofilm formation. Furthermore, this EO showed low cytotoxicity against immortalized human keratinocytes lines, but had good antioxidant activity on the same eukaryotic cellular models.

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The Tanacetum vulgare L. (Tansy) has several ethnobotanical uses, mostly related to the essential oil and sesquiterpene lactones, whereas information regarding other compounds is scarce. This research is designed to characterize the phenolic compounds (flavonoids, phenolic acids, and tannins) to analyze the thujone (which is toxic in high concentrations) content and to detect the antioxidant activity (DPPH assay) of extracts. The main highlights of our work provide a chemical profile of phenolic compounds of T. vulgare harvested from different regions of Latvia, as well as simultaneously support the ethnomedicinal uses for wild T. vulgare through the integration of phenolic compounds as one of the value constituents of leaves and flowers. The extraction yield was 18 to 20% for leaves and 8 to 16% for flowers. The total phenol content in the extracts of T. vulgare as well as their antioxidant activity was different between collection regions and the aerial parts ranging from 134 to 218 mg GAE/g and 32 to 182 mg L-1, respectively. A remarkable variation in the thujone (α + ß) content (0.4% up to 6%) was detected in the extracts. T. vulgare leaf extracts were rich in tannins (up to 19%). According to the parameters detected, the extracts of T. vulgare could be considered promising for the development of new herbal products.

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The genus Phagnalon Cass. (Asteraceae) is widely distributed from Macaronesia in the West to the Himalayas in the East, from South France and Nord Italy to Ethiopia and Arabian Peninsula. Species of this genus have been used in folk medicine of many countries as medicinal herbs and they are also used such as food. The extracts and the essential oils (EOs) of these plants have reported antimicrobial, antioxidant, antidiabetic, antitumor, etc. properties and they have different biological applications. Phagnalon sinaicum Bornm. and Kneuck. is a very rare plant native of Middle East. It grows primarily in the desert or dry scrubland biome. Its EO, never previously investigated, was analysed by GC-MS. The EO was very rich in oxygenated monoterpenes, with artemisia ketone (20.40%), α-thujone (19.36%), and santolina alcohol (13.29%) as main constituent. Some considerations with respect to all the other EOs of Phagnalon taxa studied so far were carried out.

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In this study, the capacity of eight essential oils (EOs), sage (Salvia officinalis), coriander (Coriandrum sativum), rosemary (Rosmarinus officinalis), black cumin (Nigella sativa), prickly juniper (Juniperus oxycedrus), geranium (Pelargonium graveolens), oregano (Origanum vulgare) and wormwood (Artemisia herba-alba), on the inhibition of NF-κB activation was screened at concentrations up to 0.25 µL/mL using THP-1 human macrophages bearing a NF-κB reporter. This screening selected coriander, geranium, and wormwood EOs as the most active, which later evidenced the ability to decrease over 50 % IL-6, IL-1ß, TNF-α and COX-2 mRNA expression in LPS-stimulated THP-1 macrophages. The chemical composition of selected EOs was performed by gas chromatography-mass spectrometry (GC-MS). The two major constituents (>50 % of each EO) were tested at the same concentrations presented in each EO. It was demonstrated that the major compound or the binary mixtures of the two major compounds could explain the anti-inflammatory effects reported for the crude EOs. Additionally, the selected EOs also inhibit>50 % caspase-1 activity. However, this effect could not be attributed to the major components (except for ß-citronellol/geranium oil, 40 %/65 % caspase-1 inhibition), suggesting, in addition to potential synergistic effects, the presence of minor compounds with caspase-1 inhibitory activity. These results demonstrated the potential use of the EOs obtained from Tunisian flora as valuable sources of anti-inflammatory agents providing beneficial health effects by reducing the levels of inflammatory mediators involved in the genesis of several diseases.

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The diversity of plant monoterpenes is largely based on the catalytic activity of monoterpene synthases. Additionally, copy number variation of monoterpene synthase genes may contribute to the quantity of transcripts and hence to the essential oil profile. This study used whole-genome sequencing and digital PCR for the measurement of copy number variation and quantification of gene expression in three closely related Salvia species, namely Salvia officinalis, Salvia pomifera and Salvia fruticosa. Twelve, 13 and 15 monoterpene synthase-encoding open-reading frames were predicted for Salvia officinalis, Salvia pomifera and Salvia fruticosa, respectively. In Salvia officinalis, one of the open reading frames was disrupted indicating a pseudogene. Monoterpene synthase genes were generally single copy per haploid genome, only a few were double or triple copy genes. Expression levels of monoterpene synthases in leaves corresponded generally well with essential oil composition. In some cases, a higher expression level of a certain monoterpene synthase could be explained by its duplication or triplication. The very high content of thujones in Salvia pomifera, for example, was accompanied by gene duplication and increased gene expression of (+)-sabinene synthase responsible for the thujone precursor sabinene. In Salvia officinalis, three individuals different in their essential oil profile showed significant differences in their monoterpene synthase expression levels corresponding roughly to the profile of the essential oils. Transcript expression of monoterpene synthase genes were measured in leaf, calyx and corolla. The corolla differed significantly from leaves, while calyces usually showed a profile intermediary between leaf and corolla.

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Various species of the genus Achillea L. (Asteraceae) are traditionally used worldwide for wound healing against diarrhea, flatulence, and abdominal pains, as diuretic and emmenagogue agents. In the present study, the essential oils (EOs) obtained separately from the leaves and inflorescences of wild-growing Achillea grandifolia Friv. from Mt. Menoikio and Mt. Pelion (Greece) were analyzed by Gas Chromatography-Mass Spectrometry. The major compounds found in EOs of A. grandifolia inflorescences from Mt. Menoikio were as follows: cis-thujone (36.9%), 1,8-cineole (11.9%), camphor (10.0%), ascaridole (7.3%), α-terpinene (6.4%), sabinene (4.1%), trans-thujone (3.6%), and cis-jasmone (3.4%). In leaves from Mt. Menoikio, they were as follows: cis-thujone (50.8%), 1,8-cineole (20.0%), trans-thujone (5.5%), camphor (5.5%), borneol (3.6%), and α-terpineol (3.1%). In inflorescences from Mt. Pelion, they were as follows: camphor (70.5%), camphene (5.9%), cis-jasmone (3.2%), bornyl acetate (3.2%). In leaves from Mt. Pelion, they were as follows: camphor (83.2%), camphene (3.9%), and borneol (3.7%). Subsequently, the samples were first time tested for their antioxidant activities with the interaction of EOs with DPPH (2,2-diphenyl-1-picrylhydrazyl) and their inhibition of lipid peroxidation, as well as for their anti-inflammatory activity through the soybean LOX (lipoxygenase) inhibition. All of the examined samples were found effective. A. grandifolia leaves presented the highest antioxidant potential according to the DPPH method, and the highest percentage of LOX inhibition. The study herein investigated for the first time the leaves and the inflorescences of A. grandifolia separately, and the results generally align with similar studies from neighboring countries (Turkey and Serbia) in terms of the yields and categorization of main EO compounds (oxygenated monoterpenes). However, the findings were not in agreement with previously studied Greek material, as a higher amount of cis-thujone and lower antioxidant activity are reported herein. Both the EOs of inflorescences and the leaves of the wild-growing population collected from Mt. Menoikio were characterized by a high quantity of cis-thujone (36.9% and 50.8%, respectively).

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Drought stress is known as a major yield-limiting factor in crop production that threatens food security worldwide. Arbuscular mycorrhizal fungi (AMF) and titanium dioxide (TiO2) have shown to alleviate the effects of drought stress on plants, but information regarding their co-addition to minimize the effects of drought stress on plants is scant. Here, a two-year field experiment was conducted in 2019 and 2020 to evaluate the influence of different irrigation regimes and fertilizer sources on the EO quantity and quality of sage (Salvia officinalis L.). The experiment was laid out as a split plot arranged in a randomized complete block design with three replicates. The irrigation treatments were 25, 50, and 75% maximum allowable depletion (MAD) percentage of the soil available water as non-stress (MAD25), moderate (MAD50), and severe (MAD75) water stress, respectively. Subplots were four fertilizer sources including no-fertilizer control, TiO2 nanoparticles (100 mg L-1), AMF inoculation, and co-addition of TiO2 and AMF (TiO2 + AMF). Moderate and severe drought stress decreased sage dry matter yield (DMY) by 30 and 65%, respectively. In contrast, application of TiO2 + AMF increased DMY and water use efficiency (WUE) by 35 and 35%, respectively, compared to the unfertilized treatment. The highest EO content (1.483%), yield (2.52 g m-2), and cis-thujone (35.84%, main EO constituent of sage) was obtained in MAD50 fertilized with TiO2 + AMF. In addition, the net income index increased by 44, 47, and 76% with application of TiO2 nanoparticles, AMF, and co-addition of TiO2 + AMF, respectively. Overall, the integrative application of the biofertilizer and nanoparticles (TiO2 + AMF) can be recommended as a sustainable strategy for increasing net income and improving EO productivity and quality of sage plants in drought stress conditions. Future policy discussions should focus on incentivizing growers for replacing synthetic fertilizers with proven nano and biofertilizers to reduce environmental footprints and enhance the sustainability of sage production, especially in drought conditions.

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OBJECTIVE: "Multi-targeting" drugs can prove fruitful to combat drug-resistance of multifactorial disease-cervical cancer. This study envisioned to reveal if Thuja homeopathic mother tincture (MT) and its bioactive component could combat human papillomavirus (HPV)-16-infected SiHa cervical cancer cells since it is globally acclaimed for HPV-mediated warts. METHODS: Thuja MT was studied for its antiproliferative and antimigratory properties in SiHa cells followed by microscopic determination of reactive oxygen species (ROS) generation by 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) staining and loss in mitochondrial membrane potential (MtMP) by rhodamine 123 (Rh123) staining. Apoptosis and autophagy inductions were studied by acridine orange/ethidium bromide (AO/EB) staining and immunoblot analyses of marker proteins. The bioactive component of Thuja MT detected by gas chromatography-mass spectrometry was studied for antiproliferative and antimigratory properties along with in silico prediction of its cellular targets by molecular docking and oral drug forming competency. RESULTS: Thuja MT showed significant antiproliferative and antimigratory potential in SiHa cells at a 50% inhibitory concentration (IC50) of 17.3 µL/mL. An increase in DCFDA fluorescence and loss in Rh123 fluorescence prove that Thuja MT acted through the burst of ROS and loss in MtMP respectively. AO/EB-stained cells under the microscope and immunoblot analyses supported Thuja-induced cellular demise via dual pathways-apoptosis and autophagy. Immunoblots showed cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1) along with upregulation of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B)-II, and p62 proteins. Hence, the apoptotic cascade followed a caspase-3-dependent pathway supported by PARP-1 cleavage, while autophagic death was Beclin-1-dependent and mediated by accumulation of LC3BII and p62 proteins. Thujone, detected as the bioactive principle of Thuja MT, showed greater anti-proliferative and anti-migratory potential at an IC50 of 77 µg/mL, along with excellent oral drug competency with the ability for gastrointestinal absorption and blood-brain-barrier permeation with nil toxicity. Molecular docking depicted thujone with the strongest affinity for mammalian target of rapamycin, phosphoinositide 3-kinase, and protein kinase B followed by B-cell lymphoma 2, murine double minute 2 and adenosine monophosphate-activated protein kinase, which might act as upstream triggers of apoptotic-autophagic crosstalk. CONCLUSION: Robust "multi-targeting" anticancer potential of Thuja drug and thujone for HPV-infected cervical cancer ascertained its therapeutic efficacy for HPV infections.

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Sagebrush (Artemisia spp.) are dominant wild plants in large areas of the U.S., Canada and Mexico, and they include several species and subspecies. The aim was to determine if there are significant differences in essential oil (EO) yield, composition, and biological activity of sagebrush within the Bighorn Mountains, U.S. The EO yield in fresh herbage varied from 0.15 to 1.69% for all species, including 0.25-1.69% in A. tridentata var. vaseyana, 0.64-1.44% in A. tridentata var. tridentata, 1% in A. tridentata var. wyomingensis, 0.8-1.2% in A. longifolia, 0.8-1% in A. cana, and 0.16% in A. ludoviciana. There was significant variability in the EO profile between species, and subspecies. Some EO constituents, such as α-pinene (0-35.5%), camphene (0-21.5%), eucalyptol (0-30.8%), and camphor (0-45.5%), were found in most species and varied with species and subspecies. The antioxidant capacity of the EOs varied between the species and subspecies. None of the sagebrush EOs had significant antimicrobial, antimalarial, antileishmanial activity, or contained podophyllotoxin. Some accessions yielded EO with significant concentrations of compounds including camphor, eucalyptol, cis-thujone, α-pinene, α-necrodol-acetate, fragranol, grandisol, para-cymene, and arthole. Therefore, chemotypes can be selected and possibly introduced into culture and be grown for commercial production of these compounds to meet specific industry needs.

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OBJECTIVE@#"Multi-targeting" drugs can prove fruitful to combat drug-resistance of multifactorial disease-cervical cancer. This study envisioned to reveal if Thuja homeopathic mother tincture (MT) and its bioactive component could combat human papillomavirus (HPV)-16-infected SiHa cervical cancer cells since it is globally acclaimed for HPV-mediated warts.@*METHODS@#Thuja MT was studied for its antiproliferative and antimigratory properties in SiHa cells followed by microscopic determination of reactive oxygen species (ROS) generation by 2',7'-dichlorodihydrofluorescein diacetate (DCFDA) staining and loss in mitochondrial membrane potential (MtMP) by rhodamine 123 (Rh123) staining. Apoptosis and autophagy inductions were studied by acridine orange/ethidium bromide (AO/EB) staining and immunoblot analyses of marker proteins. The bioactive component of Thuja MT detected by gas chromatography-mass spectrometry was studied for antiproliferative and antimigratory properties along with in silico prediction of its cellular targets by molecular docking and oral drug forming competency.@*RESULTS@#Thuja MT showed significant antiproliferative and antimigratory potential in SiHa cells at a 50% inhibitory concentration (IC50) of 17.3 µL/mL. An increase in DCFDA fluorescence and loss in Rh123 fluorescence prove that Thuja MT acted through the burst of ROS and loss in MtMP respectively. AO/EB-stained cells under the microscope and immunoblot analyses supported Thuja-induced cellular demise via dual pathways-apoptosis and autophagy. Immunoblots showed cleavage of caspase-3 and poly(adenosine diphosphate-ribose) polymerase-1 (PARP-1) along with upregulation of Beclin-1, microtubule-associated protein 1 light chain 3B (LC3B)-II, and p62 proteins. Hence, the apoptotic cascade followed a caspase-3-dependent pathway supported by PARP-1 cleavage, while autophagic death was Beclin-1-dependent and mediated by accumulation of LC3BII and p62 proteins. Thujone, detected as the bioactive principle of Thuja MT, showed greater anti-proliferative and anti-migratory potential at an IC50 of 77 µg/mL, along with excellent oral drug competency with the ability for gastrointestinal absorption and blood-brain-barrier permeation with nil toxicity. Molecular docking depicted thujone with the strongest affinity for mammalian target of rapamycin, phosphoinositide 3-kinase, and protein kinase B followed by B-cell lymphoma 2, murine double minute 2 and adenosine monophosphate-activated protein kinase, which might act as upstream triggers of apoptotic-autophagic crosstalk.@*CONCLUSION@#Robust "multi-targeting" anticancer potential of Thuja drug and thujone for HPV-infected cervical cancer ascertained its therapeutic efficacy for HPV infections.

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The present study analyzed the chemical composition of Juniperus foetidissima Willd. essential oils (EOs) and evaluated their attractancy and toxicity to two agriculturally important tephritid fruit flies. The composition of hydrodistilled EOs obtained from leaves (JFLEO) and fruits (JFFEO) of J. foetidissima was analyzed by GC-FID and GC-MS. The main compounds were α-pinene (45%) and cedrol (18%) in the JFLEO and α-pinene (42%), α-thujone (12%), and ß-thujone (25%) in the JFFEO. In behavioral bioassays of the male Mediterranean fruit fly, Ceratitis capitata (Wiedemann), both JFLEO and JFFEO showed strong attraction comparable to that observed with two positive controls, Melaleuca alternifolia and Tetradenia riparia EOs. In topical bioassays of the female Caribbean fruit fly, Anastrepha suspensa (Loew), the toxicity of JFFEO was two-fold higher than that of JFLEO, with the LD50 values being 10.46 and 22.07 µg/µL, respectively. This could be due to differences in chemical components between JFLEO and JFFEO. The JFFEO was dominated by 48% monoterpene hydrocarbons (MH) and 46% oxygenated monoterpenes (OM), while JFLEO consisted of 57% MH, 18% OM, and 20% oxygenated sesquiterpenes (OS). This is the first study to evaluate the attractancy and toxicity of J. foetidissima EOs to tephritid fruit flies. Our results indicate that JFFEO has the potential for application to the management of pest tephritid species, and further investigation is warranted.

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Even though several plants can improve the female reproductive function, the use of herbs, herbal preparations, or essential oils during pregnancy is questionable. This review is focused on the effects of some essential oils and their constituents on the female reproductive system during pregnancy and on the development of the fetus. The major concerns include causing abortion, reproductive hormone modulation, maternal toxicity, teratogenicity, and embryo-fetotoxicity. This work summarizes the important studies on the reproductive effects of essential oil constituents anethole, apiole, citral, camphor, thymoquinone, trans-sabinyl acetate, methyl salicylate, thujone, pulegone, ß-elemene, ß-eudesmol, and costus lactone, among others.

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The therapeutic potential of α,ß-thujone, a functional compound found in many medicinal plants of the Cupressaceae, Asteraceae, and Lamiaceae families, has been demonstrated, including in inflammation and cancers. However, its pharmacological functions and mechanisms of action in ovarian cancer remain unclear. We investigated the anticancer properties of α,ß-thujone in ES2 and OV90 human ovarian cancer cells and its effect on sensitization to cisplatin. α,ß-thujone inhibited cancer cell proliferation and induced cell death through caspase-dependent intrinsic apoptotic pathways. Moreover, α,ß-thujone-mediated endoplasmic reticulum stress was associated with the loss of mitochondrial functions and altered metabolic landscape of ovarian cancer cells. α,ß-Thujone attenuated blood vessel formation in transgenic zebrafish, implying it has significant antiangiogenic potential. In addition, α,ß-thujone sensitized ovarian cancer cells to cisplatin, causing synergistic pharmacological effects. Collectively, our results suggest that α,ß-thujone has therapeutic potential in human ovarian cancer and functions via regulating multiple intracellular stress-associated metabolic reprogramming and caspase-dependent apoptotic pathways.

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Traditionally, it is theorized that skin sensation is initiated when cutaneous sensory afferents and Merkel cells receive sensory stimuli, while epidermal keratinocytes were deemed to have no role. However, mounting evidence has shown that keratinocytes can initiate skin sensation by receiving sensory stimuli and transmitting sensory information to sensory afferents. Knowledge regarding the mechanisms by which keratinocytes receive exogenous stimuli is limited, with TRP channels and olfactory receptors having been proposed to serve as receptors for exogenous stimuli in keratinocytes. Recently, expression analyses have demonstrated the expression of multiple TAS2R genes in human skin. TAS2Rs are chemosensory GPCRs employed by taste cells to detect bitter-tasting substances. However, only subtypes TAS2R1 and TAS2R38 have been characterized in epidermal keratinocytes. We present evidence suggesting that subtype TAS2R14 is functionally expressed in epidermal keratinocytes. TAS2R14 transcripts and protein were detected in primary and N/TERT-1 keratinocytes. Additionally, keratinocytes responded to α-thujone, a TAS2R14 ligand, with an increase in intracellular free Ca2+ concentration. The tastant-evoked Ca2+ signals were found to be mediated by wild-type TAS2R14 and heterotrimeric G proteins. We conclude that TAS2R14 serves as a chemosensory receptor in epidermal keratinocytes and hypothesize that it enables the cells to recognize potentially harmful chemical substances.

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The medicinal sage plant (Salvia spp.), belonging to Lamiaceae family, is one of the most important medicinal and aromatic plants. The members of this genus are globally known due to its antimicrobial, antioxidant, astringent, spasmolytic, antihidrotic and specific sensorial properties. In this study, we investigated the potential impact of water deficit on transcript abundance, and essential oil composition of five major metabolites, i.e. 1-8 cineole, α-ß-thujone, camphor, and borneol in three genotypes of Salvia spp. Results showed that relative expression of three genes and their corresponding metabolites increased together at three stages under drought condition, but the CS gene transcript decreased independently from 1,8-cineole in garden sage. Furthermore, borneol changed differently compared to the BS gene expression in control and drought treatment plants of S. reuterana (Yasuj). The competitive synthesis of ß-thujone, and α-thujone by SS gene were demonstrated in S. officinalis and Yasuj ecotype of S. reuterana; whereas, no change was observed for Urmia ecotype of S. reuterana. There was no precursor shortage to synthesis of borneol and camphor in garden sage; however increasing the BS led to high production of borneol and low camphor in S. reuterana under drought stress. As a mechanism, secondary metabolites enable the plants to cope with unfavorable conditions, but genetic differences might affect the quantity and quality of these compounds.

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Thuja occidentalis L. (Cupressaceae) has its origins in Eastern North America and is cultivated in Europe and Brazil as an ornamental tree, being known as the "tree of life" or "white cedar". In traditional medicine, it is commonly used to treat liver diseases, bullous bronchitis, psoriasis, enuresis, amenorrhea, cystitis, uterine carcinomas, diarrhea, and rheumatism. The chemical constituents of T. occidentalis have been of research interest for decades, due to their contents of essential oil, coumarins, flavonoids, tannins, and proanthocyanidines. Pharmacology includes antioxidant, anti-inflammatory, antibacterial, antifungal, anticancer, antiviral, protective activity of the gastrointestinal tract, radioprotection, antipyretic, and lipid metabolism regulatory activity. Therefore, the present review represents the synthesis of all the relevant information for T. occidentalis, its ethnobotany, phytochemistry, and a thorough analysis of their pharmacological activities, in order to promote all the biological activities shown so far, rather than the antitumor activity that has promoted it as a medicinal species.

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Increasingly, travellers are looking for novel and unusual tourism experiences. Local produce, such as wine and food, has long been a strong visitor magnet. The search for pleasurable experiences has extended to substances that may be illegal at home, or to those surrounded by mystery. Travel medicine needs to be aware of new trends in tourism, especially if they involve substances with potential health risks, so that appropriate travel health advice can be given including the consideration of potential adverse reactions with current medications or pre-existing conditions. This article introduces a relatively new trend, 'absinthe-tourism', the mysterious drink itself, its flamboyant history and the escalating health issues in the 19th century that finally led to its ban in many countries. Absinthe is now freely available from reputable distilleries. Today, medical concern lies rather with unscrupulous suppliers on the internet, high alcohol content and adulterations. Until evidence suggests otherwise, there may be no concern for healthy travellers on the 'fairy-trail'.

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Alpha-thujone, widely used in beverages (1-5 mg/kg), is known to have cytotoxic effects, but the mode of action and the role of potential apoptotic proteins in yeast cell death should be unraveled. In this study, we used Schizosaccharomyces pombe, which is a promising unicellular model organism in mechanistic toxicology and cell biology, to investigate the involvement of pro-apoptotic factors in alpha-thujone-induced cell death. We showed alpha-thujone-induced ROS accumulation-dependent cytotoxicity and apoptosis. In addition, we used superoxide dismutase-deficient cells (sod1 and sod2 mutants) to understand the effect of oxidative stress. Alpha-thujone caused significant cytotoxicity and apoptotic cell death, particularly in sod mutants. Moreover, two potential apoptotic factors, pca1 and pnu1 (pombe caspase-1 and pombe nuc1) were investigated to understand which factor mediates alpha-thujone-induced cell death. Pca1-deficient cells showed increased survival rates and reduced apoptosis in comparison to parental cells after chemical treatment while pnu1 mutation did not cause any significant change and the response was found identical as of parental cells. Yeast responded to alpha-thujone in caspase-dependent manner which was very similar to that for acetic acid. In conclusion, alfa-thujone-induced apoptosis and accounting mechanisms, which were mediated by ROS and driven by Pca1, were clarified in the unicellular model, S. pombe.

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Thujone is a natural biologically active monoterpene ketone component of essential oils of numerous plants. The aim of the study was to evaluate the effect of ß-thujone and ß-thujone derivatives bisulfite adduct, lactone, oxime, and lactam application on behavior of Myzus persicae (Sulz.) (Hemiptera: Aphididae) during probing and settling. The choice and no-choice tests (aphid settling and Electrical Penetration Graph (EPG), respectively) revealed that stereochemistry of thujone was important for biological activity (ß-thujone caused changes in aphid behavior while α-thujone did not) and that cyclopentane ring modifications and functional groups addition gave derivatives that possessed stronger and more durable deterrent effects. The most effective modification was the incorporation of a lactam moiety into the ß-thujone molecule. Application of ß-thujone lactam limited aphid settling for at least 24 h, caused restlessness in aphids and a delay or failure in reaching phloem phase by M. persicae. ß-Thujone lactam can be considered a deterrent of medium potency with activity expressed at preingestive phase of aphid probing. Other compounds did not restrain aphid stylet penetration in non-phloem tissues but slightly limited sap ingestion (lactone, oxime), and restrained aphid settling for a period of less than 24 h (ß-Thujone, bisulphite adduct, lactone).

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Thuja occidentalis L. is indigenous for Northern America and commonly cultivated in Europe. Raw materials obtained from this tree are widely applied in the ethnomedicine and phytotherapy of numerous ailments, incl. scurvy, cystitis, rheumatism and cancer. Despite wide medicinal applications of Thuja occidentalis, still little is known on its therapeutic potential in tumor treatment. α-thujone is the main component of Thuja occidentalis essential oil, which has been suggested to possess anti-tumor activities. This monoterpene easily penetrates the blood-brain barrier. Therefore, we examined its effects on the malignancy of glioblastoma multiforme (GBM) cells, with the special emphasis on the mechanisms of its effect on cell viability and invasiveness. α-thujone exerted the attenuating effect on the viability and proliferation of GBM cells when administered at the concentrations between 100 and 500 µg/ml (660 µM - 3.2 mM). This effect was correlated with the induction of apoptosis in GBM cell populations and with considerable inhibition of GBM cells motility. Mechanistic analyses demonstrated the induction of oxidative stress and autophagy in α-thujone-treated tumor cells, whereas normal astrocytes displayed considerably lower sensitivity to α-thujone. Our observations demonstrate that α-thujone exerts pro-apoptotic and anti-invasive effects on GBM cells. They confirm the potential of α-thujone for the treatment of glioblastoma multiforme.

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