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Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of tea tree oil obtained from leaves and terminal branchlets of Melaleuca alternifolia (Maiden & Betche) Cheel when used as a sensory additive for all animal species. The EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) concluded that tea tree oil was very unlikely to be of safety concern for long‐living and reproductive animals and is of no concern for target species for fattening at the following concentrations in complete feed: 1.1 mg/kg for chickens for fattening, 1.5 mg/kg for turkeys for fattening, 1.7 mg/kg for laying hens, 2.0 mg/kg for piglets, 2.4 mg/kg for pigs for fattening, 3.1 mg/kg for sows, 5.0 mg/kg for veal calves (milk replacer) and salmonids, 4.4 mg/kg for cattle for fattening, sheep/goats and horses, 2.9 mg/kg for dairy cows, 1.8 mg/kg for rabbits, 0.9 mg/kg for cats, 5.3 mg/kg for dogs, 6.6 for crustaceans and 15 mg/kg for ornamental fish. These conclusions were extrapolated to other physiologically related species. For any other species, the additive is very unlikely to be of safety concern at 1.1 mg/kg complete feed. No concerns for consumers and the environment were identified following the use of the additive up to the highest safe use level in feed. Regarding user safety, tea tree oil should be considered as an irritant to skin and eyes and as a dermal and respiratory sensitiser. It is classified as a reprotoxic substance (category 1B) following CLP criteria and should be handled accordingly. Since M. alternifolia and its preparations were recognised to flavour food and its function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary. [ABSTRACT FROM AUTHOR]

This study investigated the antistress effects of yuzu synthetic fragrances by employing three experiments on humans and mice using two yuzu synthetic fragrances and five single compounds. We prepared two synthetic fragrances based on the component analysis of two natural yuzu essential oils extracted by cold-pressed and steam-distilled extraction methods. Chromogranin A (CgA) and heart rate (HR) were used as stress indices in human experiments. Immobility time during the forced swim test was used as a stress index in mice experiments. We analyzed brain mechanisms by measuring the expression of neurotrophic factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) in the mice experiments. Synthetic yuzu fragrance mimicked steam-distilled oil (SD) significantly reduced participants' heart rate in experiment 1. In the forced swim test conducted in experiment 2, SD significantly reduced immobility time, and increased the expression of neurotrophic factors BDNF, NGF, and NT-3 in the hippocampus of mice. In experiment 3, focusing on single compounds, terpinen-4-ol significantly reduced immobility time in the forced swim test. These findings indicate that inhalation of SD and terpinen-4-ol has antistress effects. Terpinen-4-ol is a strong candidate for further investigation as a potential stress-reducing agent. [ABSTRACT FROM AUTHOR]

In order to improve the hydrophobicity and volatility of terpinen-4-ol and extend its duration of action, β-cyclodextrin-based metal-organic framework (β-CD-MOF) was first prepared by the modified vapor diffusion method, and then terpinen-4-ol was encapsulated with the β-CD-MOF to prepare a terpinen-4-ol/β-CD-MOF inclusion complex by the solvent incubation method. The mass ratio of the prepared β-CD-MOF or β-CD used as the control to terpinen-4-ol was optimized for encapsulation. The morphological characteristics, spectral absorption properties and thermogravimetric characterisation of the terpinen-4-ol/β-CD-MOF complex were analyzed. Through in vitro bacteriostatic assays, the inhibitory effects of the complex on three food-borne pathogens were determined. The results showed that the highest drug loading and encapsulation efficiency were achieved when the mass ratio of terpinen-4-ol to β-CD-MOF was 1:1, superior to the same preparation conditions using β-CD as a carrier. Scanning electron microscope (SEM) observations indicated that irregularly arranged β-CD molecules stacked together under the bridging action of K+, forming an orderly arranged rectangular β-CD-MOF. Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analysis demonstrated terpinen-4-ol was successfully encapsulated in β-CD-MOF with hydrogen bond interactions between them. Thermogravimetric analysis (TGA) proved that the volatilization rate of terpinen-4-ol could be retarded when encapsulated by β-CD-MOF, extending its application temperature range from 30~160 ℃ to 30~350 ℃. In vitro antibacterial experiments showed that the terpinen-4-ol/β-CD-MOF complex exhibited long-lasting antibacterial abilities against three common cold-chain microorganisms, including Escherichia coli, Staphylococcus aureus and Listeria monocytogenes. In conclusion, encapsulating terpinen-4-ol in β-CD-MOF allows for effective preservation, providing a theoretical basis for the development of novel, green and safe antimicrobial materials for cold-chain applications.

Copyright of Science & Technology of Food Industry is the property of Science & Technology of Food Industry Editorial Office and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Chiliadenus montanus(Vahl.) Brullo is a wild herb that grows in narrow parts of Jordan and is locally named Hneedeh. Despite being used for treating mild abdominal and respiratory ailments, Hneedeh is still locally known on a very small scale, and its healing capabilities are still waiting for a solid scientific justification. No previous studies were made to explore the antibacterial potential of Jordanian Hneedeh as well as its chemical composition despite being researched by scientists from neighboring countries. For this reason, this research aimed to unveil the active compounds behind the medicinal properties of wild C. montanus collected from Garissa-Jordan by analyzing the essential oil using the GC MS system. Also, the antibacterial activity was explored in two extracts (methanolic and ethanolic) collected from the succulent branches of C. montanus was examined using Microdilution and Disc Diffusion Assays. Data revealed the presence of 23 compounds grouped into eight classes and oxygenated monoterpenes were the predominant class (40.36%).Terpinen-4-ol, which is known for its super curative antibacterial and antitumoral powers, was indicated to be the major chemical compound in the essential oil of Hneedeh as it comprised (23.3%) of the essential oil, which disagreed with other previous studies made on the same plants growing in neighboring counties. Moreover, both extract types restricted growth in most tested bacterial types. The results recorded in the Microdilution Assay showed that the inhibitory effect of both extract types was stronger thanthose obtained in the antibiotic treatment (control) in E. coli and Staphylococcus aureus. Meanwhile, both methanolic and ethanolic extracts were as effective as the antibiotic when administrated to Bacillus subtilis and Salmonella sp. at similar minimal inhibition concentration (MIC) values. Moreover, Disc Diffusion Assay showed that both extract types could prevent the development of six bacteria types while no effect was recorded in Klebsiella pneumoniae. However, E coli bacteria was the most affected strain. The presence of the oxygenated monoterpenes, especially Terpinen-4-ol at premium levels, might be the causal agent behind the remarkable antibacterial powers of C. montanus extract. To our knowledge, this is the first time that C. montanus which grows wild in the village of Ghareesa is reported to contain Terpinen-4-ol as the main active ingredient, which is unlike results reported in other studies conducted on similar plant species growing in other countries. [ABSTRACT FROM AUTHOR]

Terpinen-4-ol (T-4-O) is an important component of tea tree oil and has anti-inflammatory effects. Currently, there are very few studies on the mechanisms by which T-4-O improves lipopolysaccharide (LPS)-induced macrophage inflammation. In this study, LPS-stimulated mouse RAW264.7 macrophages were used as a model to analyze the effects of T-4-O on macrophage inflammatory factors and related metabolic pathways in an inflammatory environment. The results showed that T-4-O significantly decreased the expression levels of inflammatory cytokines induced by LPS. Cellular metabolism results showed that T-4-O significantly decreased the ratio of the extracellular acidification rate and oxygen consumption rate. Non-targeted metabolomics results showed that T-4-O mainly affected glutamine and glutamate metabolism and glycine, serine, and threonine metabolic pathways. qPCR results showed that T-4-O increased the transcript levels of GLS and GDH and promoted glutamine catabolism. Western blotting results showed that T-4-O inhibited the mTOR and IκB, thereby decreasing NF-κB activity. The overall results showed that T-4-O inhibited mTOR phosphorylation to promote glutamine metabolism and increased cell oxidative phosphorylation levels, thereby inhibiting the expression of LPS-induced inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Manuka oil and tea tree oil are essential oils with known antibacterial properties that are believed to be caused by one main component: terpinen-4-ol. Terpinen-4-ol has potent antibacterial activity against caries-related microorganisms. However, few studies have investigated the antimicrobial effects of terpinen-4-ol on bacteria in apical periodontitis. Thus, the objective of the present study was to evaluate the antibacterial and antibiofilm potential of terpinen-4-ol against Enterococcus faecalis , Porphyromonas gingivalis , Prevotella intermedia , and Fusobacterium nucleatum , which have all been detected in apical periodontitis. The minimum inhibitory and minimum bactericidal concentrations of terpinen-4-ol were determined to assess its activity against biofilms. The minimum inhibitory concentration of terpinen-4-ol was 0.25% against E. faecalis and F. nucleatum , 0.05% against P. gingivalis , and 0.1% against P. intermedia. The minimum bactericidal concentration of terpinen-4-ol was 1.0% against E. faecalis , 0.2% against P. gingivalis and P. intermedia , and 0.5% against F. nucleatum. In the biofilm evaluations, all terpinen-4-ol-treated bacteria had significant reductions in biofilm viability compared with controls in experiments assessing attachment inhibitory activity. Furthermore, structural alterations and decreased bacterial cell clumping were observed under scanning electron microscopy, and significantly decreased cell survival was noted using fluorescence microscopy. Together, these results suggest that terpinen-4-ol is a potential antibacterial agent with bactericidal properties, and can also act on established biofilms. [ABSTRACT FROM AUTHOR]

Harvested fresh produce is prone to massive losses during storage associated with fungal infection, and the shelf-life of seasonal nutritious strawberries is only a few days. Biodegradable antimicrobial active packaging has been suggested as a potential strategy to prolong the shelf-life of perishable products. Here, we developed a novel antimicrobial active packaging based on mung bean starch (MBS) modified with citric acid (CA) for cross-linking, and terpinen-4-ol (TP4O) as an antimicrobial additive for preservation. We found that the MBS with CA and TP4O increased film thickness, and enhanced moisture content (MC). Using MBS as the solution base maintained low water vapor permeability (WVP) in the film, this was not affected by TP4O (p > 0.05). Adding TP4O significantly reduced the total color difference (ΔE) of MBS films. The microstructure of films was assessed using scanning electron microscopy (SEM) and cross-linking was verified by Fourier transform infrared spectroscopy (FTIR). The SEM results showed increasing roughness with the incorporation of TP4O, and FTIR analysis showed that CA was well cross-linked. The results of storage tests at 20 oC under 80% RH showed that the incorporation of 0.25% TP4O led to a non-significant (p > 0.05) increase in weight loss, whereas the incorporation of 0.5% TP4O, the weight loss of the strawberries increased significantly (p < 0.05). MBS/CA/0.25% and MBS/CA/05% TP4O significantly (p < 0.05) reduced the lesion diameter of strawberries inoculated with Botrytis cinerea. The uncoated, MBS/CA/0.25%, and MBS/CA/05% TP4O each showed favorable highlights of different quality parameters of stored strawberries. Weight loss, firmness, and fungal decay were considered key parameters that greatly affect the postharvest degradation of fruits. [ABSTRACT FROM AUTHOR]

Abstract Green manure (GM) may reduce the use of chemical fertilizers, been an ecologically appropriate strategy to cultivation of medicinal plants. Crotalaria juncea, is one of the most used because it adapts to different climatic and high nitrogen content. Origanum vulgare. is widely used in cooking, pharmaceutical, cosmetic industries and food products. The objectives of this study were to evaluate the GM on biomass, essential oil (EO), phenolic and antioxidant. The experiment consisted: control; 150, 300, 450, and 600 g (Sh= leaves+steam) more 200 g roots (R); 600 g aerial part; 200 g roots; and soil with 300 g cattle manure per pot. The highest dry weights were observed in the presence of GM and cattle manure (90 days). The control had an EO production 75% lower in relation to the dose of 450 g GM (Sh+R). Principal component analysis showed that GM and cattle manure positively influenced the dry weight, content, yield, and EO constituents, and total flavonoids. The GM contributed to the accumulation of the major EO compounds (trans-sabinene hydrate, thymol, terpinen-4-ol). The GM management may be beneficial for cultivating, because it can increase the production of biomass and the active components, in addition to being an inexpensive resource.

This study investigated the antistress effects of yuzu synthetic fragrances by employing three experiments on humans and mice using two yuzu synthetic fragrances and five single compounds. We prepared two synthetic fragrances based on the component analysis of two natural yuzu essential oils extracted by cold-pressed and steam-distilled extraction methods. Chromogranin A (CgA) and heart rate (HR) were used as stress indices in human experiments. Immobility time during the forced swim test was used as a stress index in mice experiments. We analyzed brain mechanisms by measuring the expression of neurotrophic factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin-3 (NT-3) in the mice experiments. Synthetic yuzu fragrance mimicked steam-distilled oil (SD) significantly reduced participants’ heart rate in experiment 1. In the forced swim test conducted in experiment 2, SD significantly reduced immobility time, and increased the expression of neurotrophic factors BDNF, NGF, and NT-3 in the hippocampus of mice. In experiment 3, focusing on single compounds, terpinen-4-ol significantly reduced immobility time in the forced swim test. These findings indicate that inhalation of SD and terpinen-4-ol has antistress effects. Terpinen-4-ol is a strong candidate for further investigation as a potential stress-reducing agent.

Objective To investigate the synergistic bacteriostatic effect of terpinen-4-ol (T4O) and α-bisabolol (Bis) on Staphylococcus aureus (S.aureus) and Cutibacterium acnes (C.acnes). Methods The microdilution checkerboard technique was used to determine the minimum inhibitory concentration (MIC) of T4O combined with Bis on the two etu perimental bacteria, and fractional inhibitory concentration index (FICI) was calculated. An MIC group (T4O and Bis at a concentration of MIC), a 2×MIC group (T4O and Bis at a concentration of 2×MIC), and a negative control group (no T4O or Bis added) were set up for each experimental bacterium; the time-bactericidal curve was plotted for each experimental bacterium after the addition of both T4O and Bis; each group of the two experimental bacteria was measured in terms of Zeta potential (ZP) on the surface of the strain, leakage of intracellular nucleic acid and protein, damage of bacterial biofilm, and respiratory chain dehydrogenase activity in S.aureus after the addition of both T4O and Bis; a transmission electron microscope was used to observe the influence of T4O combined with Bis on the morphology of the two experimental bacteria. Results The combination of T4O and Bis for S.aureus and C.acnes had an FICI of

Lung cancer is the second most commonly diagnosed cancer and has the highest mortality rate worldwide despite the remarkable advances in its treatment. Origanum majorana Essential Oil (OMEO) has been shown to be effective against non-small cell lung cancer (NSCLC) cells, decreasing their viability and colony growth in vitro, as well as inhibiting tumor growth in chick embryo chorioallantoic membranes (CAM) and nude mice in vivo. OMEO is mainly composed of four monoterpenes, namely terpinen-4-ol, sabinene hydrate, α-terpinene, and γ-terpinene. In this study, we aimed to investigate the potential anticancer effects of these monoterpenes, either alone or in combination, on NSCLC. Our findings indicate that these four monoterpenes significantly decreased NSCLC cell viability in a concentration-dependent manner, reduced their colony growth in vitro, and also downregulated survivin expression in these cells. Moreover, different combined mixtures of these monoterpenes further enhanced their anticancer effects on cellular viability, with a terpinen-4-ol and sabinene hydrate combination being the most potent. We also found that terpinen-4-ol, in combination with sabinene hydrate, markedly enhanced the anticancer effect of the individual monoterpenes on NSCLC viability within a shorter treatment duration through, at least in part, survivin downregulation. Furthermore, this combination enhanced the inhibition of colony growth in vitro and the tumor growth of NSCLC cells xenografted onto chick embryo CAM in vivo. Altogether, our study highlights the potential of these monoterpenes for use in further pre-clinical investigations against various cancer hallmarks. [ABSTRACT FROM AUTHOR]

Context: Tea tree oil (TTO) is an essential oil derived from Melaleuca alternifolia, with high antimicrobial and antifungal potential. Unfortunately, its topical antifungal efficacy is limited because it is volatile, thermolabile and easily oxidized. A formulation has been developed to overcome this problem by encapsulating TTO in a nanostructured lipid carrier (NLC). Aims: To determine the effect of the liquid to solid lipid ratio on the physicochemical properties and the stability of TTO-loaded NLC. Methods: Five formula of TTO-loaded NLCs were produced by high shear homogenization method and characterized according to their particle size, size distribution, polydispersity, zeta potential, thermal characteristics, X-ray diffraction, and terpinen-4-ol concentration. In addition, a stability study was conducted by observing its physical and chemical characteristics during storage in the refrigerator (4 ± 2°C) and at room temperature (27 ± 2°C) for six months. Results: The resulting TTO-loaded NLC had an average droplet size under 400 nm. The particle size increases with increasing amount of liquid lipid in the formula. There were insignificant changes in organoleptic properties, polydispersity index, zeta potential and terpinene-4-ol concentration during stability study for six months. However, the particle size slightly increased during the six months of storage. Furthermore, the NLC 3, which formulated with a 25:95 ratio liquid to solid lipid, was be chosen as the best formula, since it demonstrated the best physicochemical characteristic and stability. Conclusions: TTO-loaded NLC with good physicochemical characteristics and stability has been successfully developed. In addition, NLC 3 is considered as the best NLC formula, which exhibits characteristics and stability that meet the requirements.

Terpinen-4-ol (T-4-O) is an important component of tea tree oil and has anti-inflammatory effects. Currently, there are very few studies on the mechanisms by which T-4-O improves lipopolysaccharide (LPS)-induced macrophage inflammation. In this study, LPS-stimulated mouse RAW264.7 macrophages were used as a model to analyze the effects of T-4-O on macrophage inflammatory factors and related metabolic pathways in an inflammatory environment. The results showed that T-4-O significantly decreased the expression levels of inflammatory cytokines induced by LPS. Cellular metabolism results showed that T-4-O significantly decreased the ratio of the extracellular acidification rate and oxygen consumption rate. Non-targeted metabolomics results showed that T-4-O mainly affected glutamine and glutamate metabolism and glycine, serine, and threonine metabolic pathways. qPCR results showed that T-4-O increased the transcript levels of GLS and GDH and promoted glutamine catabolism. Western blotting results showed that T-4-O inhibited the mTOR and IκB, thereby decreasing NF-κB activity. The overall results showed that T-4-O inhibited mTOR phosphorylation to promote glutamine metabolism and increased cell oxidative phosphorylation levels, thereby inhibiting the expression of LPS-induced inflammatory cytokines.

Terpenes and their derivatives in essential oil have been raising an upstream interest due to their unwavering health-promoting effects and safety profiles, although the individual essential oil components are inadequately assessed for their biological potential. Terpinen-4-ol, a bioactive natural terpene-derivative unambiguously distributed in most essential oil sources, is displaying a very remarkable role as a phytometabolite. This review, therefore, deciphered the health-promoting effects of Terpinen-4-ol in oxidative stress-linked diseases including neurodegenerative disorders, cancers, cardiovascular diseases, diabetes, and inflammatory disorders. Using Google as a search engine, this systematic review unraveled 217 relevant articles out of 857 search results from Web of Science, PubMed, and ScienceDirect. Terpinen-4-ol is reported to increase superoxide dismutase, decrease glutathione-S-transferase and acetylcholine esterase, inhibit NF-κB and NLRP3 inflammasome activation pathway, downregulate the α-amylase activity and increase insulin sensitivity, and substantially inhibit the generation of inflammatory mediators such as IL-1β, IL-6, IL-10. Despite several beneficial actions of Terpinen-4-ol, it has hardly been expedited to use as pharmaceutical therapeutic target for unveiled biological activities. In that context, this review has focused on the role of Terpinen-4-ol in attenuating oxidative stress and stress-linked pathophysiological conditions unraveling a research gap on it to manifest its best pharmaceutical and therapeutic uses.

BACKGROUND: Terpinen-4-ol has been found to have a significant antibacterial activity against pathogenic bacteria associated with peri-implantitis and can reduce the formation of surface biofilm and the occurrence of peri-implantitis when applied to the surface of titanium implants; however, the studies regarding its biosafety are lacking. OBJECTIVE: To explore the antibacterial effects of terpinen-4-ol on Staphylococcus aureus and Streptococcus mutans and its effect on the growth and osteogenic differentiation of MC3T3-E1 cells. METHODS: Different concentrations of terpinen-4-ol were dissolved in dimethyl sulfoxide. The minimum inhibitory concentration and minimum bactericidal concentration of pineolene 4 alcohol solution against Staphylococcus aureus and Streptococcus mutans were tested. The 1/2 minimum inhibitory concentration, minimum inhibitory concentration, and minimum bactericidal concentration of pineolene 4 alcohol were tested by bacteriostatic zone test. MC3T3-E1 cells were treated with different concentrations (0%, 0.3%, 0.2%, 0.1%, v/v) of terpinen-4-ol in medium or calcification-inducing solution. The proliferation activity of cells was detected by CCK-8 assay. Cells were stained with rhodamine-phalloidin to observe cytoskeleton. Differentiation ability of cells was detected by alkaline phosphatase activity assay. The formation of mineralized nodules was observed by alizarin red staining. The mRNA expression of Runx2 and osteocalcin was detected by real-time reverse transcription-polymerase chain reaction. RESULTS AND CONCLUSION: (1) Minimum inhibitory concentration and minimum bactericidal concentration of terpinen-4-ol against Streptococcus mutans were 0.1% (v/v) and 0.4% (v/v) respectively and against Staphylococcus aureus were 0.03% (v/v) and 0.125% (v/v) respectively. With the increase of the concentration of terpinen-4-ol, the diameter of bacteriostatic zone was significantly increased (P < 0.05). (2) CCK-8 assay showed that terpinen-4-ol promoted the proliferation of MC3T3-E1 cells, with the most obvious effects in the 0.2% group. (3) Rhodamine-phalloidin staining showed that terpinen-4-ol promoted the adhesion of MC3T3-E1 cells. (4) Alkaline phosphatase activity assay and alizarin red staining showed that terpinen-4-ol promoted the early differentiation and mineralization of MC3T3-E1 cells, with the most obvious effects in the 0.2% group. (5) Real-time reverse transcription-polymerase chain reaction showed that the mRNA expression of Runx2 was significantly higher in the 0.3%, 0.2%, and 0.1% groups than in the 0% group at 1 day of calcification induction (P < 0.05), and the mRNA expression of Runx2 and osteocalcin was significantly higher in the 0.2% and 0.1% groups than in the 0.3% and 0% groups at 7 and 14 days of calcification induction (P < 0.05). (6) These results indicate that terpinen-4-ol can inhibit the growth of Staphylococcus aureus and Streptococcus mutans and promote the proliferation, differentiation and mineralization of MC3T3-E1 cells. [ABSTRACT FROM AUTHOR]

Azorean Cryptomeria japonica is widely used for local wood production, generating large amounts of aerial-part biomass residues that can be a sustainable source of value-added bioproducts. This comparative study aimed (i) to determine the yield and chemical profile of the essential oils (EOs) extracted by hydrodistillation from Azorean C. japonica foliage, leaves, male cones (MCs), and female cones (FCs), and (ii) to investigate the antimicrobial and brine shrimp lethality (BSL) effects of the obtained EOs and some major components. The EOs yield revealed a wide range (ca. 1–3%, w/d.w.) and their chemical composition, analysed by GC–MS and GC–FID, showed the presence of seventy-one components. Monoterpene hydrocarbons (38–71%) dominated in all the studied EOs, mainly α-pinene (17–45% of total EOs), decreasing as follows: cone EOs > leaf EOs > foliage EOs. Oxygen-containing monoterpenes (mainly terpinen-4-ol) also dominated in cone EOs. Contrariwise, oxygen-containing sesquiterpenes (mainly elemol) and diterpene hydrocarbons (mainly phyllocladene) dominated in foliage/leaf EOs. The studied EOs exhibited activity against Gram-positive bacteria but no activity against Gram-negative bacteria. A similar trend was displayed by α-pinene. Only the cone EOs showed antifungal activity against Penicillium chrysogenum, but this was significantly lower than those of α-pinene and terpinen-4-ol. Moreover, FC EO should also be considered for further investigation due to its high toxicity on BSL bioassay. In conclusion, this study demonstrated the variability of yield, chemical profile, and bioactivities in the EOs from different parts of the Azorean C. japonica, expanding the knowledge of the potentialities of C. japonica aerial-part EOs, particularly the ones from the cone samples. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Zhejiang University: Science B is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

According to previous research, turmeric seeds exhibit anti-inflammatory, anti-malignancy, and anti-aging properties due to an abundance of terpinen-4-ol (T4O). Although it is still unclear how T4O works on glioma cells, limited data exist regarding its specific effects. In order to determine whether or not glioma cell lines U251, U87, and LN229 are viable, CCK8 was used as an assay and a colony formation assay was performed using different concentrations of T4O (0, 1, 2, and 4 μM). The effect of T4O on the proliferation of glioma cell line U251 was detected through the subcutaneous implantation of the tumor model. Through high-throughput sequencing, a bioinformatic analysis, and real-time quantitative polymerase chain reactions, we identified the key signaling pathways and targets of T4O. Finally, for the measurement of the cellular ferroptosis levels, we examined the relationship between T4O, ferroptosis, and JUN and the malignant biological properties of glioma cells. T4O significantly inhibited glioma cell growth and colony formation and induced ferroptosis in the glioma cells. T4O inhibited the subcutaneous tumor proliferation of the glioma cells in vivo. T4O suppressed JUN transcription and significantly reduced its expression in the glioma cells. The T4O treatment inhibited GPX4 transcription through JUN. The overexpression of JUN suppressed ferroptosis in the cells rescued through T4O treatment. Taken together, our data suggest that the natural product T4O exerts its anti-cancer effects by inducing JUN/GPX4-dependent ferroptosis and inhibiting cell proliferation, and T4O will hope-fully serve as a prospective compound for glioma treatment. [ABSTRACT FROM AUTHOR]

The Mediterranean basin represents a rich source of medicinal and aromatic plants. These species contain different metabolites such as phenolics, flavonoids, tannins, coumarins and sterols known for their beneficial properties. The essential oils (EOs) of Lavandula austroapennina and Lavandula angustifolia from the Pollino massif (southern Italy) were characterized using gas chromatography-mass spectrometry and their anti-denaturation effect was assessed using in vitro models with heat-treated bovine serum albumin (BSA) chosen as a protein model. L. austroapennina EO showed a better in vitro anti-denaturation activity compared to L. angustifolia, with IC50 values equal to 260.4 ± 4.2 and 480.0 ± 2.6 µg/mL, respectively. In order to relate the observed results to the most interesting identified phytochemicals, some major components were also tested. Linalool and terpinen-4-ol proved to be effective in protecting BSA from heat denaturation. Moreover, the inhibitory properties on nitric oxide production were verified in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Both lavender EOs showed concentration-dependent inhibitory properties, as well as the monoterpene linalool. Taken together, these results suggest that L. austroapennina EO and its main constituent linalool could be good candidates for further investigations, aimed at finding new drugs with anti-arthritic potential. [ABSTRACT FROM AUTHOR]

Cytochrome P450 proteins (CYPs) in insects can encode various detoxification enzymes and catabolize heterologous substances, conferring tolerance to insecticides. This study describes the identification of a P450 gene (CYP6BQ8) from Tribolium castaneum (Herbst) and investigation of its spatiotemporal expression profile and potential role in the detoxification of terpinen-4-ol, a component of plant essential oils. The developmental expression profile showed that TcCYP6BQ8 expression was relatively higher in early- and late-larval stages of T. castaneum compared with other developmental stages. Tissue expression profiles showed that TcCYP6BQ8 was mainly expressed in the head and integument of both larvae and adults. The expression profiling of TcCYP6BQ8 in developmental stages and tissues is closely related to the detoxification of heterologous substances. TcCYP6BQ8 expression was significantly induced after exposure to terpinen-4-ol, and RNA interference against TcCYP6BQ8 increased terpinen-4-ol-induced larval mortality from 47.78 to 66.67%. This indicates that TcCYP6BQ8 may be involved in T. castaneum 's metabolism of terpinen-4-ol. Correlation investigation between the CYP6BQ8 gene and terpinen-4-ol resistance in T. castaneum revealed that the TcCYP6BQ8 gene was one of the factors behind T. castaneum 's resistance to terpinen-4-ol. This discovery may provide a new theoretical foundation for future regulation of T. castaneum. [ABSTRACT FROM AUTHOR]

Highlights The chemical composition of M. alternifolia EO was identified by GC–MS. The EO of M. alternifolia and its components, terpinen-4-ol and γ-terpinene, had potent bioactivity against S. littoralis. M. alternifolia EO and their components, terpinen-4-ol and γ-terpinene have great potential as a biopesticide in integrated pest management programs.

Abstract In this paper, the chemical constituents, larvicidal and antimicrobial activities of hydrodistilled essential oils from Zingiber castaneum Škorničk. & Q.B. Nguyễn and Zingiber nitens M.F. Newman were reported. The main constituents of Z. castaneum leaf were bicyclogermacrene (24.8%), germacrene D (12.9%), cis-β-elemene (11.2%) and β-pinene (10.3%), while sabinene (22.9%) and camphene (21.2%) were the significant compounds in the rhizome. However, the dominant compounds in the leaf of Z. nitens includes β-pinene (45.8%) and α-pinene (10.7%). Terpinen-4-ol (77.9%) was the most abundant compound of the rhizome. Z. castaneum rhizome oil displayed larvicidal activity against Aedes aegypti and Culex quinquefasciatus with LC50 values of 121.43 and 88.86 µg/mL, respectively, at 24 h. The leaf oil exhibited activity with LC50 values of 39.30 µg/mL and 84.97 µg/mL, respectively. Also, the leaf and rhizome oils of Z. nitens displayed greater larvicidal action towards Ae. aegypti with LC50 values of 17.58 µg/mL and 29.60 µg/mL, respectively. Only the rhizome oil displayed toxicity against Cx. quinquefasciatus with LC50 value of 64.18 µg/mL. All the studied essential oils inhibited the growth of Pseudomonas aeruginosa ATCC25923 with minimum inhibitory concentration (MIC) value of 50.0 µg/mL. This paper provides information on the larvicidal and antimicrobial potentials of Z. castaneum and Z. nitens essential oils.

The antimicrobial properties of essential oil from Lavandula sp. raise hopes related to its use in phytotherapy. This study aimed to evaluate the antimicrobial activity of essential oils from cultivars of L. angustifolia ('Hidcote Blue Strain', 'Hidcote Blue') and L. × intermedia ('Phenomenal', 'Grosso') grown in central-eastern Poland, that is, at the border of the northern lavender cultivation range. The chemical composition of the essential oils was determined by GC/MS. Essential oil concentrations (20, 10, 5, 2.5, 1.25, 0.6, 0.3, 0.16, 0.08, and 0.04 mg/mL) were tested to determine the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) or minimum fungicidal concentration (MFC) towards ten strains of Gram-positive bacteria, five Gram-negative bacteria, and eight yeasts in vitro culture. Essential oils from the Lavendula cultivars showed antimicrobial activity against all microorganisms analysed. The yeasts were characterised by higher sensitivity to lavender oil compared to bacteria, while Gram-positive bacteria were more sensitive than Gram-negative bacteria. The lowest MIC values for bacteria and fungi were obtained for 'Grosso'. Furthermore, the 'Grosso' oil showed the highest fungicidal activity, while the highest bactericidal activity was found in 'Hidcote Blue' and 'Grosso'. Using Staphylococcus aureus as an example, it was shown that different bacterial strains of the same species show varying sensitivity to the essential oil. A higher oil content was noted for the cultivars L. × intermedia, especially for the 'Phenomenal'. Linalyl acetate and linalool were the main components of the essential oil in all cultivars. However, in the 'Grosso' oil, a high content of terpinen-4-ol (18.08%) was also recorded. An analysis of the relationships between the content of the main components in the analysed essential oils and the antimicrobial activity of essential oils suggested that linalool and terpinen-4-ol were compounds potentially responsible for antimicrobial activity. The obtained results allow us to conclude that essential oil with significant antimicrobial activity can be obtained from Lavandula sp. plants harvested in the northern part of the cultivation range. [ABSTRACT FROM AUTHOR]

Origanum majorana is a medicinal and aromatic plant that belongs to the Lamiaceae family. It is cultivated in several parts of the world and, due to its splendid aroma and taste, is widely used for culinary purposes and in perfumes. The essential oil of the plant, to which is attributed its aroma, contains many secondary metabolites with valuable biological activity. One of them is the pesticide activity, which has attracted much interest. Given the necessity of replacing synthetic pesticides, essential oils are studied in an attempt to find naturally derived products. Thus, the aim of this review paper is to discuss the chemical profile of O. majorana essential oil and to present data regarding its insecticidal, repellent and fumigant activity. Data were collected from 1992 to 2022. Databases, including PubMed, Google Scholar, ScienceDirect and Scopus, were used for the research, and keywords, including O. majorana, sweet marjoram, essential oil, volatiles, pesticide, insecticide and repellent activity, were used. The results of this review paper indicate that O. majorana essential oil can be an alternative agent to manage pests. However, still, much research should be conducted to evaluate its toxicity against beneficial insects and to ensure its safety for human health. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a major public health issue raising growing concern in the face of dwindling response options. It is therefore urgent to find new anti-infective molecules enabling us to fight effectively against ever more numerous bacterial infections caused by ever more antibiotic-resistant bacteria. In this quest for new antibacterials, essential oils (or compounds extracted from essential oils) appear to be a promising therapeutic option. In the present work, we investigate the potential antibacterial synergy between a combination of terpinen-4-ol and α-terpineol (10:1) compared to standard tea tree oil. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined. Then, time kill assays, in vitro cytotoxicity and bactericidal activity on latent bacteria (persisters) were investigated. Finally, an in silico study of the pharmacokinetic parameters of α-terpineol was also performed. Altogether, our data demonstrate that the combination of terpinen-4-ol and α-terpineol might be a precious weapon to address ESKAPE pathogens. [ABSTRACT FROM AUTHOR]

Our aim was to verify the modulative TP-4-ol capacity in 4-nitroquinoline-1-oxide induced oral rat cancer. The stereoisomers of TP-4-ol were used against the human tongue squamous cell line and the negative stereoisomer showed lower IC50. Thirty-one Holtzman rats (120–130 g) were cancer-induced by 4-nitroquinoline-1-oxide (4-NQO/8 weeks/25 ppm) and 32 Holtzman rats (120–130 g) were used to healthy and TP-4-ol toxicity experiments. Six groups were used, healthy, 0.1nL/g of TP-4-ol, 8nL/g of TP-4-ol, 4-NQO, 4-NQO + 0.1nL/g of TP-4-ol, and 4-NQO + 8nL/g of TP-4-ol. We performed the toxicity analysis by biochemical and histopathological analysis. The biochemistry analysis includes alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate transaminase (AST), urea, and creatinine and the histopathology analysis includes the liver, kidney, lung, and spleen. Specifically, for malign modulation, we performed a macroscopic and microscopic analysis. The group exposed to 0.1nL/g of TP-4-ol demonstrated a reduced risk of malignancy in dysplasia considering the criteria of architecture and cytology. Similarly, a drop of percentual rats with SCC diagnosis was observed in 4-NQO + 0.1nL/g (41.6%) when compared to 4-NQO (87.5%). Moreover, the 4-NQO group presented a median of 2.62 SCC/rat and the 4-NQO + 0.1nL/g demonstrated a median of 0.75 SCC/rat. For toxicity analysis, 4-NQO + 0.1nL/g showed focal necrosis in the kidney and 4-NQO showed lung hemorrhagic areas. The concentration of 0.1nL/g was more effective in reducing the tongue induction of potentially malignant and malignant lesions by 4-NQO. A kidney toxicity was observed in healthy animals exposed to 0.1nL/g of TP-4-ol. The negative isoform of terpinen-4-ol negatively modulates the development of potentially malignant and malignant lesions in rats (Rattus nonverdicts albinos, Holtzman) exposed to 4-NQO. (-)-Terpinen-4-ol reduced the mice percentual with squamous cell carcinoma, 87.5 to 41.6%, and decreased the cancer/rat ratio of 2.62 in 4-NQO to 0.75 in 4-NQO + 0.1nL/g. This represents 52.4% by group and 71.3% in the cancer/rat ratio. [ABSTRACT FROM AUTHOR]

Abstract Background This study investigated the effects of terpinen-4-ol on methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm, and the possible mechanisms governing this effect. Results We observed that terpinen-4-ol has good antibacterial activity and inhibits the formation of MRSA biofilm. The MIC and MBC values for terpinen-4-ol against S. aureus were 0.08% ~ 0.32%. And terpinen-4-ol at 0.32% could kill all bacteria and clear all biofilms. Untargeted metabolomic and transcriptomic analyses showed that terpinen-4-ol strongly inhibited DNA and RNA biosynthesis in MRSA at 2 h after treatment by affecting genes and metabolites related to purine and pyrimidine metabolic pathways. Some differential genes which play important roles in DNA synthesis and the production of eDNA from biofilm exposed to terpinen-4-ol was also significantly decreased compared with that of the control. Conclusions Terpinen-4-ol has good antibacterial activity and significantly inhibits the formation of MRSA biofilm by inhibiting purine and pyrimidine metabolism.

BACKGROUND: Harmonia axyridis Pallas (Coleoptera: Coccinellidae) is an important natural enemy of aphids. Plant species and plant health conditions can affect the behavior of H. axyridis. To determine plant effects on this lady beetle, we examined beetle responses to four cover crops: coriander (Coriadrum sativum L., Apiales: Apiaceae), marigold (Tagetes erecta L., Asterales: Asteraceae), sweet alyssum (Lobularia maritima L., Brassicales: Brassicaceae), and alfalfa (Medicago sativa L., Fabales: Fabaceae). Our goal was to better understand this predator's ovipositional behavior in response to different plants and its olfactory response to the aphid‐induced volatiles from these plants. RESULTS: We found that this lady beetle did not have any significant oviposition preference among the four plant species, but H. axyridis preferred to lay eggs on the lower surface of leaves, regardless of the plant species. H. axyridis females had a significant preference for aphid‐infested marigolds, but were not attracted by any of the other three cover plants or marigolds without aphid damage. Compared to the uninfested marigold plants, the emission of 12 compounds significantly increased on the aphid‐infested marigolds, and two of them were attractive to H. axyridis under suitable concentrations. CONCLUSION: H. axyridis did not show any significant oviposition preference among the four cover crops. Aphid‐infested marigolds can attract H. axyridis. Indole and terpinen‐4‐ol mediated lady beetle attraction. These synomones have potential for manipulating populations of H. axyridis as a component of conservation biological control. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

According to previous research, turmeric seeds exhibit anti-inflammatory, anti-malignancy, and anti-aging properties due to an abundance of terpinen-4-ol (T4O). Although it is still unclear how T4O works on glioma cells, limited data exist regarding its specific effects. In order to determine whether or not glioma cell lines U251, U87, and LN229 are viable, CCK8 was used as an assay and a colony formation assay was performed using different concentrations of T4O (0, 1, 2, and 4 μM). The effect of T4O on the proliferation of glioma cell line U251 was detected through the subcutaneous implantation of the tumor model. Through high-throughput sequencing, a bioinformatic analysis, and real-time quantitative polymerase chain reactions, we identified the key signaling pathways and targets of T4O. Finally, for the measurement of the cellular ferroptosis levels, we examined the relationship between T4O, ferroptosis, and JUN and the malignant biological properties of glioma cells. T4O significantly inhibited glioma cell growth and colony formation and induced ferroptosis in the glioma cells. T4O inhibited the subcutaneous tumor proliferation of the glioma cells in vivo. T4O suppressed JUN transcription and significantly reduced its expression in the glioma cells. The T4O treatment inhibited GPX4 transcription through JUN. The overexpression of JUN suppressed ferroptosis in the cells rescued through T4O treatment. Taken together, our data suggest that the natural product T4O exerts its anti-cancer effects by inducing JUN/GPX4-dependent ferroptosis and inhibiting cell proliferation, and T4O will hope-fully serve as a prospective compound for glioma treatment.

Owing to their extensive biological potential, essential oils (EOs) and their bioactive phytochemicals have gained attention from the scientific community. Within this domain, Terpinen-4-ol (T-4-ol), a bioactive monoterpene alcohol and the major constituent of tea tree oil (TTO), has made its way into translational research. Recent literature on T-4-ol strongly indicates its diverse pharmacological properties, including but not limited to antimicrobial, antivirulent, anti-oxidant, anti-inflammatory, anti-hypertensive, and anti-cancer effects. Hence, this review is the first to provide a comprehensive overview of the sources, bioavailability, safety, pharmaceutical delivery systems, and multifaceted biological properties of T-4-ol, emphasizing its medicinal potential for widescale application. The antibacterial and antifungal effectiveness of T-4-ol has been discussed, encompassing its role in combating a broad spectrum of bacterial and fungal pathogens. The review delves into the antivirulent prospects of T-4-ol, shedding light on its ability to attenuate virulence and mitigate bacterial pathogenesis. Scientific literature on the anti-oxidant and anti-inflammatory activity of T-4-ol highlighting its role in neutralizing reactive oxygen species and modulating inflammatory pathways has also been collated. Furthermore, the review elaborates on the cardioprotective and anti-hypertensive properties of T-4-ol and augments literature on its anti-cancer mechanism against various cancer cell lines. The review also provides in-depth knowledge of the pharmaceutical formulations of T-4-ol and recent knowledge about its application in clinical/field trials. The exploration of these diverse attributes positions T-4-ol as a promising candidate for further research and therapeutic repurposing in various biomedical applications. [Display omitted] • Terpinen-4-ol or 4-carvomenthenol is the principle bioactive component of tea tree oil. • Terpinen-4-ol is a multifaceted phytochemical with diverse pharmacological properties. • It displays broad-range antibacterial, antifungal, and antivirulence properties against multiple pathogens. • The phytochemical exhibits quorum quenching potential against drug-resistant pathogens. • Terpinen-4-ol harbors notable anti-inflammatory, anti-oxidant, anti-hypertensive, and cardioprotective effects. • In vitro and in vivo investigations have highlighted its profound anti-cancer properties. [ABSTRACT FROM AUTHOR]

Legionella pneumophila (Lp), responsible for a severe pneumonia called Legionnaires' disease, represents an important health burden in Europe. Prevention and control of Lp contamination in warm water systems is still a great challenge often due to the failure in disinfection procedures. The aim of this study was to evaluate the in vitro activity of Terpinen-4-ol (T-4-ol) as potential agent for Lp control, in comparison with the essential oil of Melaleuca alternifolia (tea tree) (TTO. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of T-4-ol were determined by broth micro-dilution and a micro-atmosphere diffusion method to investigate the anti-Lp effects of T-4-ol and TTO vapors. Scanning Electron Microscopy (SEM) was adopted to highlight the morphological changes and Lp damage following T-4-ol and TTO treatments. The greatest antimicrobial activity against Lp was shown by T-4-ol with a MIC range of 0.06–0.125% v/v and MBC range of 0.25–0.5% v/v. The TTO and T-4-ol MIC and MBC decreased with increasing temperature (36 °C to 45 ± 1 °C), and temperature also significantly influenced the efficacy of TTO and T-4-ol vapors. The time-killing assay showed an exponential trend of T-4-ol bactericidal activity at 0.5% v/v against Lp. SEM observations revealed a concentration- and temperature- dependent effect of T-4-ol and TTO on cell surface morphology with alterations. These findings suggest that T-4-ol is active against Lp and further studies may address the potential effectiveness of T-4-ol for control of water systems. [ABSTRACT FROM AUTHOR]

Background: Spodoptera littoralis is mostly controlled by the use of synthetic insecticides. Nonetheless, the use of these insecticides causes a slew of issues. On this pest, the antifeedant activity of Melaleuca alternifolia essential oil (EO) and its two principal components was investigated. Results: The gas chromatography–mass spectrometry (GC/MS) analysis revealed that the M. alternifolia EO was composed of eleven compounds. Terpinen-4-ol (40.1%) and γ-terpinene (21.9%) were chosen as the major constituents. In terms of antifeedant efficacy, treatment with M. alternifolia EO and these components reduced leaf consumption and the efficiency of food conversion in larvae in a concentration-dependent manner. When compared to untreated larvae, weight, growth, and pupation percentage were all significantly lower. Conclusions: The findings show that M. alternifolia EO and its components, terpinen-4-ol and γ-terpinene can be effectively combined for cotton leafworm management. Highlights: The chemical composition of M. alternifolia EO was identified by GC–MS. The EO of M. alternifolia and its components, terpinen-4-ol and γ-terpinene, had potent bioactivity against S. littoralis. M. alternifolia EO and their components, terpinen-4-ol and γ-terpinene have great potential as a biopesticide in integrated pest management programs. [ABSTRACT FROM AUTHOR]

To evaluate the improvement of ocular signs and symptoms in patients suffering from Demodex blepharitis using a combined treatment approach: use of eyelid wipes impregnated with 2.5% terpinen-4-ol (T4O) and 0.2% hyaluronic acid (HA) in the initial treatment period and investigation of maintenance of the treatment effect with the use of eyelid cleansing wipes. Fifty patients with Demodex blepharitis were treated in the initial treatment period with sterile eyelid T4O impregnated wipes for 28 days. In the following four-week maintenance period, 82% patients received sterile eyelid maintenance wipes, while 16% continued treatment with T4O impregnated wipes. Global ocular discomfort, adapted TOSS, SANDE score, and individual blepharitis symptoms were assessed by patients at day 28 and day 56. Ocular signs were evaluated by the investigator at the study visits. Investigator's assessment of the overall treatment performance, patient's assessment of treatment satisfaction, and tolerability were evaluated with questionnaires. All global ocular discomfort symptoms and disease specific symptoms assessed by patients as well as all parameters evaluated by the investigators significantly improved in the initial treatment period with the application of eyelid wipes impregnated with 2.5% terpinen-4-ol until day 28. The therapeutic effect was maintained or even improved during the maintenance period under administration of mainly eyelid maintenance wipes until day 56. Both products were well tolerated. No adverse events and no clinically relevant changes in visual acuity were observed during both periods. Once daily treatment with T4O impregnated eyelid wipes in the initial treatment period significantly improved the ocular symptoms and signs and reduced the mite count in patients with Demodex blepharitis within four-weeks administration. Subsequent maintenance treatment with maintenance wipes for another 4 weeks preserved or further intensified the treatment success. The products were well tolerated and were convenient to use. [ABSTRACT FROM AUTHOR]

Simple Summary: Long noncoding RNAs (lncRNAs) are important regulatory factors in multiple biological processes, including genomic imprinting, cancer, RNA interference, and protein translation. Several lncRNAs can respond to insecticides. However, lncRNA functions associated with terpinen-4-ol resistance in the red flour beetle (Tribolium castaneum) have not yet been identified. In previous work, we found terpinen-4-ol to have strong fumigation activity against store-product pests. As a pesticide from plants, terpinen-4-ol shows nearly no residual danger to the environment; however, resistance is inevitable if people use terpinen-4-ol immoderately. To avoid resistance to terpinen-4-ol occurring in the red flour beetle, we deeply sequenced and tried to find some lncRNAs that can regulate target mRNA expression to reduce terpinen-4-ol. Long noncoding RNAs (lncRNAs) are important regulatory factors in multiple biological processes, and several lncRNAs are known to respond to insecticides. However, the lncRNA functions that are associated with terpinen-4-ol resistance in the red flour beetle (Tribolium castaneum) have not yet been identified. In this study, we determined the differentially transcribed lncRNAs between fumigated and control experimental groups. In the six libraries that underwent RNA sequencing, 34,546 transcripts were identified, including 8267 novel lncRNAs, 4155 novel mRNAs, 1151 known lncRNAs, and 20,973 known mRNAs. Among these, we found that the expression of 1858 mRNAs and 1663 lncRNAs was significantly different in the fumigated group compared with the control group. Among the differentially transcribed lncRNAs, 453 were up-regulated and 1210 were down-regulated lncRNAs. In addition, we identified the regulatory function targets of the lncRNAs. Functionally, all lncRNAs and target genes associated with terpinen-4-ol metabolism were enriched in several metabolic pathways, like the ATP-binding cassette transporter, pentose interconversion, and glucuronate interconversion. To the best of our knowledge, this study represents the first global identification of lncRNAs and their potential association with terpinen-4-ol metabolism in the red flour beetle. These results will provide reference information for studies on the resistance to terpinen-4-ol and other essential oil compounds and chemical pesticides, as well as an understanding of other biological processes in T. castaneum. [ABSTRACT FROM AUTHOR]

Numerous plant-based repellents are widely used for personal protection against host-seeking mosquitoes. Vitiveria zizanioides (L.) Nash essential oil and its constituents have demonstrated various mosquito repellent activities. In this study, three chemical actions of vetiver oil and five constituents (terpinen-4-ol, α-terpineol, valencene, vetiverol and vetivone) were characterized against Aedes aegypti, Aedes albopictus and Culex quinquefasciatus by using the high-throughput screening assay system (HITSS). Significant contact escape responses in Ae. aegypti and Ae. albopictus to all test compounds at concentrations between 2.5 and 5% were observed. Spatial repellency responses were also observed in some tested mosquito populations depending upon concentrations. The most significant toxic response on mosquitoes was found at the highest concentration, except for vetivone which had no toxic effect on Ae. aegypti and Ae. albopictus. Results on phototoxic and genotoxic hazard revealed that vetiver oil and their constituents showed no phototoxic potential or any significant genotoxic response. In conclusion, vetiver oil and two constituents, valencene and vetiverol, are potentials as active ingredients for mosquito repellency and present no toxicity.

Background: This study investigated the effects of terpinen-4-ol on methicillin-resistant Staphylococcus aureus (MRSA) and its biofilm, and the possible mechanisms governing this effect. Results: We observed that terpinen-4-ol has good antibacterial activity and inhibits the formation of MRSA biofilm. The MIC and MBC values for terpinen-4-ol against S. aureus were 0.08% ~ 0.32%. And terpinen-4-ol at 0.32% could kill all bacteria and clear all biofilms. Untargeted metabolomic and transcriptomic analyses showed that terpinen-4-ol strongly inhibited DNA and RNA biosynthesis in MRSA at 2 h after treatment by affecting genes and metabolites related to purine and pyrimidine metabolic pathways. Some differential genes which play important roles in DNA synthesis and the production of eDNA from biofilm exposed to terpinen-4-ol was also significantly decreased compared with that of the control. Conclusions: Terpinen-4-ol has good antibacterial activity and significantly inhibits the formation of MRSA biofilm by inhibiting purine and pyrimidine metabolism. [ABSTRACT FROM AUTHOR]

Purpose: To investigate in vitro effects of active ingredients in eye cleansing wipes and solutions on the life span of Demodex.Methods: Demodex mites were extracted by eyelash epilation method from volunteers who were found to have chronic demodex blepharitis during an ophthalmological examination. Preparations with three or more motile, live adult Demodex parasites were included in the study. Two drops of the test solution were dropped on the samples: saline, 2% tea tree oil (TTO; Osto®, AKD Medical products, Turkey), 7.5% TTO (Blefaritto®, Jeomed, Turkey), and 0.5% terpinen-4-ol (T4O; Blefastop plus®, NTC, Italy). Under light microscopy at 100× and 400× magnification, samples were examined and followed. The average killing time of Demodex was noted for each preparation.Results: The study was analyzed on 120 patient samples. In the control group with saline, the average killing time of Demodex had an average of 323.5 ± 21.1 min. In other groups, an average mean of 95.9 ± 25.2 min in the 2% TTO group, 67.1 ± 21.8 min in the 7.5% TTO group, and 27.3 ± 6.0 min in the 0.5% T4O group was observed. It was found that the 0.5% T4O group was significantly more effective than the other groups.Conclusion: Chronic Demodex blepharitis treatment is quite difficult in ophthalmology practice. It appears that, even at very low concentrations, T4O has an effective anti-Demodex effect. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is a major public health issue raising growing concern in the face of dwindling response options. It is therefore urgent to find new anti-infective molecules enabling us to fight effectively against ever more numerous bacterial infections caused by ever more antibiotic-resistant bacteria. In this quest for new antibacterials, essential oils (or compounds extracted from essential oils) appear to be a promising therapeutic option. In the present work, we investigate the potential antibacterial synergy between a combination of terpinen-4-ol and α-terpineol (10:1) compared to standard tea tree oil. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined. Then, time kill assays, in vitro cytotoxicity and bactericidal activity on latent bacteria (persisters) were investigated. Finally, an in silico study of the pharmacokinetic parameters of α-terpineol was also performed. Altogether, our data demonstrate that the combination of terpinen-4-ol and α-terpineol might be a precious weapon to address ESKAPE pathogens.

Purpose: To report a successful treatment of chronic rosacea associated ocular demodicosis with lid scrub containing terpinen-4-ol (T4O). Observations: A 72-year old woman presented with recurrent and refractory ocular erythema, irritation, dryness, and photophobia despite conventional medical treatment (artificial tears, hypochlorous acid lid hygiene, doxycycline, and erythromycin) for 5 years. Examination revealed facial erythema, telangiectasias on cheeks, nose and lids, and cylindrical dandruff (CD) on bilateral upper and lower lashes. Epilation sampling confirmed demodicosis. After treatment with lid wipe containing T4O (Cliradex, Biotissue, Miami, FL) over face and lids, ocular discomfort, CD, facial and eyelid erythema, telangiectatic vessels were significantly reduced. Complete eradication of demodex mites and resolution of symptoms and signs lasted 8 months of follow-up. Conclusions: This case suggests that T4O is effective in treating chronic rosacea associated ocular demodex blepharitis.

Vibrio parahaemolyticus outbreaks emphasize the urgency of highly efficient prevention strategies to control this foodborne pathogen. This study investigated the antibacterial effects of terpinen-4-ol on V. parahaemolyticus RIMD2210633 and explored the underlying mechanism via RNA-seq analysis. The results showed that terpinen-4-ol inhibited V. parahaemolyticus efficiently with minimum inhibitory concentration and minimum bactericidal concentration values at 0.8 μL/mL. Scanning electron microscopy and PI/SYTO 9 staining assay demonstrated that cell morphology and cell membrane integrity were dose-dependently destructed. Additionally, biofilm formation was significantly inhibited according to crystal violet and MTT assay analysis. Notably, terpinen-4-ol showed good inhibitory activity against V. parahaemolyticus on salmon fillets via fumigation at 4 °C. Transcriptional analysis revealed significant downregulation of genes participated in cell wall formation (oppB , oppF), cell membrane integrity, pilus assembly protein, biofilm formation and cell motility (ToxR , LuxR), capsular polysaccharide biosynthesis protein, type IV pilin MshA and mannose-sensitive haemagglutinin type-IV pili (MSHA) biogenesis protein (MshJ , MshJ , MshK , MshL , MshN). The results demonstrated that terpinen-4-ol can efficiently inhibit the growth and pathogenicity of V. parahaemolyticus. With its safety and pleasant odor, terpinen-4-ol can be developed as a natural antibacterial substance to tackle V. parahaemolyticus contamination in food preservation and prevent associated diseases. [Display omitted] • Terpinen-4-ol inhibited V. parahaemolyticus with MIC and MBC values at 0.8 μL/mL. • Terpinen-4-ol destroyed V. parahaemolyticus cell morphology and membrane integrity. • Terpinen-4-ol inhibited V. parahaemolyticus cell motility and biofilm formation. • Terpinen-4-ol inhibited V. parahaemolyticus growth on salmon fillet via fumigation. • Terpinen-4-ol repressed gene expression of cell wall and biofilm formation. [ABSTRACT FROM AUTHOR]

Riadh Messaoud,1 Lamia El Fekih,2,3 Anis Mahmoud,1 Hager Ben Amor,4 Radhouane Bannour,5 Serge Doan,6,7 Moncef Khairallah41Department of Ophthalmology, Tahar Sfar University Hospital, Mahdia, Tunisia; 2Department of Ophthalmology, Internal Security Forces Hospital, La Marsa, Tunisia; 3Faculty of Medicine, Tunis-El Manar University, Tunis, Tunisia; 4Fattouma Bourguiba University Hospital, Monastir, Tunisia; 5Ophthalmology Private Practice, Monastir, Tunisia; 6Department of Ophthalmology, Bichat Hospital, Paris, France; 7Fondation A de Rothschild, Paris, FrancePurpose: To evaluate the clinical improvement in ocular symptoms and signs in patients suffering from Demodex anterior blepharitis after using a novel cleansing wipe impregnated with 2.5% terpinen-4-ol and 0.2% hyaluronic acid.Study design: This was an exploratory, multicenter, open, randomized, two-parallel group comparative study.Methods: Forty-eight patients with Demodex anterior blepharitis were randomly assigned to apply the sterile wipe T1172 (Blephademodex®), either once daily (n=24, Group 1) or twice daily (n=24, Group 2) for 29 days. Overall ocular discomfort and other individual symptoms were measured using a 0–10 numeric rating scale at Day 8 and Day 29. Ocular signs, including eyelid margin hyperemia and number of cylindrical dandruff, were examined at slit lamp. Overall treatment performance by investigator, patient satisfaction and tolerance were evaluated with questionnaires.Results: Overall ocular discomfort was significantly reduced from baseline (p

Abstract Origanum vulgare L. (Lamiaceae) is a widespread flavoring culinary and medicinal herb. The present study aimed at investigating the antimicrobial activity of Origanum vulgare (OV) essential oil (EO) through illustrating its biostatic, biocidal and the dynamics of the biocidal activity against 11 different microorganisms. GC/MS of OV EO allowed the identification of 32 compounds representing 99.94% of the oil. The two major identified compounds were terpinen-4-ol (38.35%) and trans-sabinene hydrate (10.06%). Different methods were employed to illustrate the biostatic activity of OV EO. Results of the biostatic studies on OV EO using agar and broth dilution methods showed that Staphylococcus aureus (S. aureus) was the most sensitive organism; with a Minimum inhibitor concentration (MIC) 1.18 mg/ml. Agar diffusion method showed that the highest activity was observed against Bordetella bronchiseptica (Br. bronchiseptica), Saccharomyces cerevisiae (S. cerevisiae), Bacillus subtilis (B. subtilus) and Staphylococcus epidermidis (S. epidermidis) with inhibition zones 38 ± 1.5, 29.5 ± 0.8, 26.9 ± 0.9 and 26.9 ± 1.1 mm, respectively. Studying the dynamics of 1% v/v OV essential oil emulsion over a period of 6 h revealed that Escherichia coli (E. coli), B. subtilis, S. epidermidis and S. cerevisiae had the fastest response. Also increasing concentrations of OV oil emulsion increased the rate of cell killing and the duration of growth lag phase increased correspondingly. These data indicated that OV EO produces a concentration and time-dependent antimicrobial activity.

Legionella pneumophila (Lp), responsible for a severe pneumonia called Legionnaires’ disease, represents an important health burden in Europe. Prevention and control of Lp contamination in warm water systems is still a great challenge often due to the failure in disinfection procedures. The aim of this study was to evaluate the in vitro activity of Terpinen-4-ol (T-4-ol) as potential agent for Lp control, in comparison with the essential oil of Melaleuca alternifolia (tea tree) (TTO. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of T-4-ol were determined by broth micro-dilution and a micro-atmosphere diffusion method to investigate the anti-Lp effects of T-4-ol and TTO vapors. Scanning Electron Microscopy (SEM) was adopted to highlight the morphological changes and Lp damage following T-4-ol and TTO treatments. The greatest antimicrobial activity against Lp was shown by T-4-ol with a MIC range of 0.06–0.125% v/v and MBC range of 0.25–0.5% v/v. The TTO and T-4-ol MIC and MBC decreased with increasing temperature (36 °C to 45 ± 1 °C), and temperature also significantly influenced the efficacy of TTO and T-4-ol vapors. The time-killing assay showed an exponential trend of T-4-ol bactericidal activity at 0.5% v/v against Lp. SEM observations revealed a concentration- and temperature- dependent effect of T-4-ol and TTO on cell surface morphology with alterations. These findings suggest that T-4-ol is active against Lp and further studies may address the potential effectiveness of T-4-ol for control of water systems.

Serine proteases are a class of hydrolytic enzymes involved in various physiological functions like digestion, coagulation, fibrinolysis and immunity. The present study evaluates the serine protease inhibitory potential of phytochemicals liquiritin and terpinen-4-ol present in the herb Glycyrrhiza glabra L. using trypsin as the model enzyme. In silico studies showed that both the compounds have a significant binding affinity towards trypsin with a binding energy of -26.66 kcal/mol and -19.79 kcal/mol for liquiritin and terpinen-4-ol, respectively. Their binding affinity was confirmed through in vitro enzyme inhibition assays. The mode of inhibition was found to be uncompetitive. In order to explain the mode of inhibition, docking of the ligands to the enzyme-substrate complex was also done and binding energy was calculated after MD simulation. The energy values showed that the binding affinities of these compounds towards the enzyme substrate complex are more than that towards the enzyme alone. This explains the uncompetitive mode of inhibition.Communicated by Ramaswamy H. Sarma.

Long noncoding RNAs (lncRNAs) are important regulatory factors in multiple biological processes, and several lncRNAs are known to respond to insecticides. However, the lncRNA functions that are associated with terpinen-4-ol resistance in the red flour beetle (Tribolium castaneum) have not yet been identified. In this study, we determined the differentially transcribed lncRNAs between fumigated and control experimental groups. In the six libraries that underwent RNA sequencing, 34,546 transcripts were identified, including 8267 novel lncRNAs, 4155 novel mRNAs, 1151 known lncRNAs, and 20,973 known mRNAs. Among these, we found that the expression of 1858 mRNAs and 1663 lncRNAs was significantly different in the fumigated group compared with the control group. Among the differentially transcribed lncRNAs, 453 were up-regulated and 1210 were down-regulated lncRNAs. In addition, we identified the regulatory function targets of the lncRNAs. Functionally, all lncRNAs and target genes associated with terpinen-4-ol metabolism were enriched in several metabolic pathways, like the ATP-binding cassette transporter, pentose interconversion, and glucuronate interconversion. To the best of our knowledge, this study represents the first global identification of lncRNAs and their potential association with terpinen-4-ol metabolism in the red flour beetle. These results will provide reference information for studies on the resistance to terpinen-4-ol and other essential oil compounds and chemical pesticides, as well as an understanding of other biological processes in T. castaneum.

ABSTRACT The aim of this study was to evaluate the efficacy and safety of several anesthetics in the brachyuran crab Neohelice granulata, an emergent experimental model. The essential oils (EOs) of Lippia alba, Aloysia tryphilla, and Melaleuca alternifolia (tea tree oil; TTO), the isolated compounds eugenol, menthol, terpinen-4-ol, and the nanoencapsulated form of TTO, were administered in one or more of the following ways: added to the water (immersion), through an arthrodial membrane (injected), or by oral gavage. Unexpectedly, most EOs did not produce an anesthetic effect after immersion. Only TTO and eugenol induced anesthesia by immersion, with very long induction and recovery times compared to anesthesia of other crustaceans. However, a good anesthetic effect was observed with the injection of terpinen-4-ol and nanoencapsulated TTO in N. granulata; both demonstrated ideal induction and recovery times. These substances appear to be promising anesthetic alternatives for crustaceans.

The present study was focused on exploring the presence of active compounds in Origanum majorana essential oil (OmEO), and its various knock‐down effects against the rice moth, Corcyra cephalonica. GC–MS analysis detected the existence of major compounds such as monoterpenes, cis‐β‐terpineol and terpinen‐4‐ol with the total proportion of 52.16%. Fumigant toxicity against adult and larvae was calculated with an LC50 value of 11.31 and 49.83 μL/L air, respectively. The contact toxicity against adult, pupa, larvae and eggs was observed with LC50 value 2.54, 0.95, 2.78, and 0.49 μL/L, respectively. Furthermore, the influential repellent behavior against adults has been observed. Acetylesterase (AChE) inhibition activity of OmEO was observed against adult and larvae of C. cephalonica with an IC50 value of 35.89 and 118.54 μL/mL, respectively. Moreover, computational docking study revealed the binding affinity of Cis‐β‐terpineol and terpinen‐4‐ol towards the active binding sites of AChE. On the other hand, Fluorescence‐assisted cytometry and comet assay confirmed the cytotoxic and genotoxic effect of OmEO at various concentrations on C. cephalonica. Altogether, the results showed the knock‐down effect of OmEO against C. cephalonica, and it could be a potential biocontrol measure against the stored product pest. [ABSTRACT FROM AUTHOR]

Essential oil from leaf, root, and stem of Peperomia pellucida native to different countries have been isolated and characterized. Variations in the chemical composition of the essential oil from the same part of the plant were established. Meanwhile, the root essential oil of P. pellucida native to Nigeria has not been studied. This work aimed at characterizing the root essential oil of P. pellucida growing in Nigeria. To achieve this, pulverized roots (500 g) of P. pellucida were hydrodistilled and yielded 0.03±0.12 % (w/w) of essential oil. Analysis of the essential oil using GC and GC/MS showed the presence of twenty-three chemical compounds. The essential oil was predominated by sesquiterpenoids, which constituted 87.5 % of the oil. Monoterpenoids constituted 2.9 % of the oil. β-fernesene (22.2 %) was the most predominant compound in the essential oil. Other principal constituents of the oil were; β-bisabolene (14.8 %), β-bergamotene (10.7 %), 1,4- cadinadiene (7.4 %), α-copaene (6.6 %) and isosativene (6.5 %). Terpinen-4-ol (2.3 %) was the major monoterpenoid in the oil, while neryl acetate (0.6 %) existed in appreciable quantity. The predominance of β- fernesene in the oil implied that the oil was of β-farnesene chemotype. [ABSTRACT FROM AUTHOR]

Tea tree oil (TTO) and its two characteristic components (terpinen-4-ol and 1,8-cineole) have been shown to inhibit Botrytis cinerea growth. In this study, we conducted a transcriptome analysis to determine the effects of TTO and its characteristic components, alone and in combination, against B. cinerea. Most differentially expressed genes (DEGs) from B. cinerea cells treated with terpinen-4-ol participated in the biosynthesis of secondary metabolites, and the metabolism of amino acids, carbohydrates, and lipids. All treatments containing terpinen-4-ol potentially induced mitochondrial dysfunction and oxidative stress. These were further confirmed by the decreased activities of several enzymes (e.g., succinate dehydrogenase (SDH), malate dehydrogenase (MDH), α-ketoglutarate dehydrogenase (α-KGDH), isocitrate dehydrogenase (ICDH)), the increased activities of certain enzymes (e.g., catalase (CAT), peroxidase (POD), superoxide dismutase (SOD)), and increased content of hydrogen peroxide (H2O2). 1,8-Cineole mainly affected DEGs involved in genetic information processing, resulting in cell death. This study provides insight into the molecular mechanism of B. cinerea inhibition by TTO, and explains the synergistic effect of terpinen-4-ol and 1,8-cineole on B. cinerea. [ABSTRACT FROM AUTHOR]