Therapeutic potential of α,ß-thujone through metabolic reprogramming and caspase-dependent apoptosis in ovarian cancer cells.

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.

Functionally expressed bitter taste receptor TAS2R14 in human epidermal keratinocytes serves as a chemosensory receptor.

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.

Maternal Reproductive Toxicity of Some Essential Oils and Their Constituents.

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.

Chemical Composition of Essential Oils from Leaves and Fruits of Juniperus foetidissima and Their Attractancy and Toxicity to Two Economically Important Tephritid Fruit Fly Species, Ceratitis capitata and Anastrepha suspensa.

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.

Involvement of Pca1 in ROS-mediated apoptotic cell death induced by alpha-thujone in the fission yeast (Schizosaccharomyces pombe).

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.

Thuja occidentalis L. (Cupressaceae): Ethnobotany, Phytochemistry and Biological Activity.

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.

The effects of water deficit on the expression of monoterpene synthases and essential oils composition in Salvia ecotypes.

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.

ß-Thujone and Its Derivatives Modify the Probing Behavior of the Peach Potato Aphid.

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).

Voltammetric determination of thujone in herbal matrices in the presence of Triton X-100.

A simple, sensitive and rapid method of low concentration of thujone determination using Controlled Growth Mercury Drop Electrode and Differential Pulse Voltammetry was described. The reduction of thujone in phosphoric acid or potassium nitrate, involves a quasi-reversible and adsorption-controlled two-electron process. In voltammetric experiments the addition of ethanol and Triton X-100 is recommended. Experimental conditions, such as composition of supporting electrolyte, concentration of Triton X-100 and operation parameters were established. The optimal electrolyte should contain: 0.04 mol L-1 phosphoric acid (pH = 1.9) or 0.05 mol L-1 potassium nitrate (pH = 6.4), 0.0002% Triton X-100 and 9.6% ethanol. The calibration graph was linear from 0.7 to 140 mgL-1 of thujone in H3PO4 as supporting electrolyte and from 0.7 to 115 mgL-1 of the analyte in KNO3. The detection limit was 0.4 mgL-1 in H3PO4 and 0.6 mgL-1 in KNO3, with the correlation coefficient of 0.998. The influence of interfering substances, such as Al(III), Bi(III), Cd(II), Cr(III), Cu(II), Pb(II), Tl(I), V(III) and Zn(II) was studied. The proposed method was validated by the thujone recovery study from the specially prepared spiked herbal matrices and alcohol extract. The considered real sample was thuja oil, in which thujone was successfully determined. All measurements were performed without sample preparation.

Pro-apoptotic and anti-angiogenic properties of the α /ß-thujone fraction from Thuja occidentalis on glioblastoma cells.

The most aggressive type of brain tumor is glioblastoma multiforme, which to date remains incurable. Thuja occidentalis is used in homeopathy for the treatment of cancer, however, its mechanism of action remains unknown. We set out to study the effects of thujone fractions of Thuja on glioblastoma using in vitro and in vivo models. We found that the α/ ß-thujone fraction decrease the cell viability and exhibit a potent anti-proliferative, pro-apoptotic and anti-angiogenic effects in vitro. In vivo assays showed that α /ß-thujone promotes the regression of neoplasia and inhibits the angiogenic markers VEGF, Ang-4 and CD31 into the tumor.

CHEMOTYPIC Variation in Volatiles and Herbivory for Sagebrush.

Plants that are damaged by herbivores emit complex blends of volatile compounds that often cause neighboring branches to induce resistance. Experimentally clipped sagebrush foliage emits volatiles that neighboring individuals recognize and respond to. These volatiles vary among individuals within a population. Two distinct types are most common with either thujone or camphor as the predominate compound, along with other less common types. Individuals respond more effectively to cues from the same type, suggesting that some of the informative message is contained in the compounds that differentiate the types. In this study, we characterized the chemical profiles of the two common types, and we examined differences in their microhabitats, morphologies, and incidence of attack by herbivores and pathogens. Analysis by gas chromatography coupled with mass spectrometry revealed that the camphor type had higher emissions of camphor, camphene, and tricyclene, while the thujone type emitted more α-thujone, ß-thujone, (Z)-salvene, (E)-salvene, carvacrol, and various derivatives of sabinene. We were unable to detect any consistent morphological or microhabitat differences associated with the common types. However, plants of the thujone type had consistently higher rates of damage by chewing herbivores. One galling midge species was more common on thujone plants, while a second midge species was more likely to gall plants of the camphor type. The diversity of preferences of attackers may help to maintain the variation in volatile profiles. These chemical compounds that differentiate the types are likely to be informative cues and deserve further attention.

Inhibitory effects of carvone isomers on the GABAA receptor in primary cultures of rat cortical neurons.

Carvone is a natural terpene which can be purified as R-(-) or S-(+) enantiomers. There are many reports about its antibacterial, antifungal, and insecticide activities, and also of some effects on the nervous system, where both enantiomers showed different potencies. Considering that the GABA(A) receptor is a major insecticide target, we studied the pharmacological activity of both carvone enantiomers, and of thujone as a reference compound acting on the receptor, on native GABA(A) by determining their effects on benzodiazepine recognition sites using primary neuronal cultures. Both isomers were able to inhibit the GABA-induced stimulation of [(3)H]flunitrazepam binding, suggesting their interaction with the GABA(A) receptor as negative allosteric modulators. Their activity was comparable to that described for thujone in the present article, with the R-(-)-carvone being the more similar and potent stereoisomer. The different configuration of the isopropenyl group in position 5 thus seems to be significant for receptor interaction and the bicycle structure not to be critical for receptor recognition. The concentrations necessary to induce negative modulation of the receptor were not cytotoxic in a murine neuron culture system. These results confirm that, at least partially, the reported insecticidal activity of carvones may be explained by their interaction with the GABA(A) receptor at its noncompetitive blocker site.

Essential-oil diversity of Salvia tomentosa Mill. in Greece.

Salvia tomentosa essential oils from Greece were studied for the first time here. The oils from five populations growing in Mediterranean pine forests on the island of Thassos (northern Aegean Sea) and from 14 populations situated in deciduous forests in Thrace (northeastern Greek mainland) were investigated. Their essential-oil contents ranged from 1.1 to 3.3% (v/w, based on the dry weight of the plant material). The populations from Thassos had high contents of α-pinene (18.0 ± 2.9%), 1,8-cineole (14.7 ± 3.0%), cis-thujone (14.0 ± 6.9%), and borneol (12.8 ± 2.2%) and smaller amounts of camphene, camphor, and ß-pinene, whereas the populations from Thrace showed high α-pinene (16.7 ± 4.0%), ß-pinene (22.8 ± 4.5%), camphor (18.3 ± 4.3%), and camphene (10.3 ± 2.4%) contents, much lower 1,8-cineole and borneol amounts, while cis-thujone was completely lacking. The comparison of the present results with published data showed that oils having cis-thujone as one of the main compounds were reported for the first time here. Multivariate statistical analyses indicate that the observed essential-oil variation was related to geographical and environmental factors.

Toxicokinetics of α-thujone following intravenous and gavage administration of α-thujone or α- and ß-thujone mixture in male and female F344/N rats and B6C3F1 mice.

Plants containing thujone have widespread use and hence have significant human exposure. α-Thujone caused seizures in rodents following gavage administration. We investigated the toxicokinetics of α-thujone in male and female F344/N rats and B6C3F1 mice following intravenous and gavage administration of α-thujone or a mixture of α- and ß-thujone (which will be referred to as α,ß-thujone). Absorption of α-thujone following gavage administration was rapid without any dose-, species-, sex- or test article-related effect. Absolute bioavailability of α-thujone following administration of α-thujone or α,ß-thujone was generally higher in rats than in mice. In rats, females had higher bioavailability than males following administration of either test article although a sex difference was not observed in mice. Cmax and AUC∞ increased greater than proportional to the dose in female rats following administration of α-thujone and in male and female mice following administration of α,ß-thujone suggesting possible saturation of elimination kinetics with increasing dose. Dose-adjusted AUC∞ for male and female rats was 5- to 15-fold and 3- to 24-fold higher than mice counterparts following administration of α-thujone and α,ß-thujone, respectively (p-value<0.0001 for all comparisons). Following both intravenous and gavage administration, α-thujone was distributed to the brains of rats and mice with females, in general, having higher brain:plasma ratios than males. These data are in support of the observed toxicity of α-thujone and α,ß-thujone where females were more sensitive than males of both species to α-thujone-induced neurotoxicity. In general there was no difference in toxicokinetics between test articles when normalized to α-thujone concentration.

Comparison of different extraction methods for the determination of α- and ß-thujone in sage (Salvia officinalis L.) herbal tea.

Salvia officinalis L. (sage) is an important industrial plant used both for food and pharmaceutical purposes. The terpene fraction of this plant is responsible for many of its therapeutic and culinary properties. We used different extraction methods Tenax TA® purge and trap, headspace (HS) solid-phase microextraction, HS sorptive extraction, and stir bar sorptive extraction to analyze the terpene fraction extracted from sage tea by GC-MS. Twenty compounds were identified, including α-, ß-thujone, and several other oxygenated monoterpenes (1,8-cineole, linalool, camphor, boneol, and bornyl acetate) and oxygenated sesquiterpenes (caryophyllene oxide, viridiflorol, humulene epoxide I, II, and III). Tenax TA® and HS sorptive extraction extracted a lower number of identified compounds, whereas HS solid-phase microextraction allowed the complete extraction of volatiles with particular reference to α- and ß-thujone. The importance of the determination of thujones content in sage herbal tea is also discussed.

Chemopreventive and antioxidant activity of the chamazulene-rich essential oil obtained from Artemisia arborescens L. growing on the Isle of La Maddalena, Sardinia, Italy.

The essential oils of Artemisia arborescens growing in Sardinia (Italy), collected during three plant growth stages, i.e., from the vegetative stage to post-blooming time, were characterized. Moreover, the in vitro antiproliferative and antioxidant activities of the oil isolated from aerial parts collected in February were evaluated. The essential oils belonged to the ß-thujone/chamazulene chemotype, notably with the highest amount of chamazulene (ca. 52%) ever detected up to now in the genus Artemisia and, in general, in essential oils. Quantitative variations in the oil composition were observed as the plant passes from the vegetative to the blooming stage. The oil was tested for its potential tumor cell growth-inhibitory effect on T98G, MDA-MB 435S, A375, and HCT116 human cell lines, using the MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay. The highest activity was observed on A375 and HCT116 cell lines, with IC50 values of 14 µg/ml. Moreover, the in vitro antioxidant and free radical-scavenging assays revealed the oil to be an effective scavenger of the ABTS radical cation, with an activity comparable to that of Trolox(®) . These results support the use of A. arborescens oil for the treatment of inflamed skin conditions. Finally, the composition of the polar fraction of the A. arborescens aerial parts was also examined, and the main component detected was 5-O-caffeoylquinic acid, which was identified for the first time in this plant.

Chemical Profiling and Antioxidant Activity of Tanacetum vulgare L. Wild-Growing in Latvia.

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.

Exploring the Medicinal Potential of Achillea grandifolia in Greek Wild-Growing Populations: Characterization of Volatile Compounds, Anti-Inflammatory and Antioxidant Activities of Leaves and Inflorescences.

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).

The chemical composition of the aerial parts essential oil of Phagnalon sinaicum collected in the Negev Desert (Israel).

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.

The Biological Properties of the Essential Oil from the Jordan Accession of Phagnalon sinaicum Bornm. & Kneuck.

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.