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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]

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]

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]

Terpinen-4-ol has potent antifungal activity and controls decay in postharvest strawberry fruit. In order to overcome the unstable and volatile characteristics of terpinen-4-ol, a γ-cyclodextrin (γ-CD) metal-organic framework (MOF) with high porosity and large specific surface area was synthesized by vapor diffusion and ultrasonic mixing. Terpinen-4-ol-loaded γ-CD-MOF (γ-CD-MOF/Ter) was then prepared using physical adsorption. Scanning electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy analysis, and nitrogen adsorption-desorption showed that terpinen-4-ol was successfully loaded into the center of the γ-CD-MOF structure, and that encapsulation efficiency and drug loading reached 53.61% and 9.31%, respectively. γ-CD-MOF/Ter reduced the release rate of terpinene-4-ol, and exhibited the higher antifungal effect against B. cinerea in vitro test. Meanwhile, it was effective in controlling gray mold and maintaining the quality of strawberry fruit. We conclude that γ-CD-MOF loads terpinen-4-ol and reduces its volatilization and has potential application in the preservation of strawberry fruit. • γ-CD-MOF was prepared using vapor diffusion combined with ultrasonic mixing. • Terpinen-4-ol was loaded into γ-CD-MOF with high encapsulation efficiency. • γ-CD-MOF/Ter has good thermal stability and sustainably releases terpinen-4-ol. • γ-CD-MOF/Ter has in vitro and in vivo anti-fungal properties. [ABSTRACT FROM AUTHOR]

Abstract Terpenes – the essential oil components - due to confirmed antimicrobial effect can be applied e.g. as ecological pesticides instead of synthetic and environmentally hazardous compounds. A practical use of these systems must be proceeded by the analysis of the properties and activity of a given mixture. In this paper the monolayers at the air/water solution interface were applied to verify the influence of eucalyptol/terpinen-4-ol mixtures on plant pathogen Botrytis cinerea model membrane. The experiments included the measurements of the surface pressure – area isotherms for model membranes on water and terpene solutions as well as terpenes penetration into lipid monolayers. In the studies done for particular terpenes stronger ability of terpinen-4-ol over eucalyptol to incorporate into membrane, alter the membrane lateral elasticity and decrease its stability was found. Based on the results for the mixtures composed of terpenes in various concentrations it was found that not only the concentration of the system but also its composition, namely the proportion of both terpenes, determines the influence on lipid system. Moreover, terpinen-4-ol, but not eucalyptol, even in low concentrations, was of strong influence on membrane activity of total mixture. Additionally, it was suggested that terpinen-4-ol acts as penetration enhancer for eucalyptol into the model membrane system. Highlights • Eucalyptol and terpinen-4-ol change elasticity of model Botrytis cinerea membrane. • Both concentration and composition of terpene mixture define its properties. • Terpnene-4-ol enhances penetration of eucalyptol into model plant pathogen membrane. [ABSTRACT FROM AUTHOR]

Nanoemulsions of Zanthoxylum rhetsa (Roxb.) DC fruit extract combined with eucalyptus oil (ZRNEs) were formulated using mixed surfactants at various Tween 80/Span 80 mass ratios of 20/80 (ZRNE-6), 50/50 (ZRNE-10), and 80/20 (ZRNE-13). These formulations had corresponding hydrophilic-lipophilic balance (HLB) values of 6, 10, and 13, respectively. Effect of the HLB on properties of the nanoemulsions were evaluated. Among these formulations, ZRNE-10, was found to be optimal for loading ZR extract with eucalyptus. It exhibited the smallest particle size of 402 ± 12 nm with a PDI of 0.41 ± 0.01, as analyzed by dynamic light scattering technique. ZRNE-10 showed the highest encapsulation efficiency for terpinen-4-ol at 83.42 ± 0.51%. It demonstrated a gradual release profile, releasing 30% of terpinen-4-ol within 48 h in a pH 7.4 PBS buffer at 37 °C. Interestingly, higher HLB values accelerated the release rate of terpinen-4-ol. The release kinetics of ZRNE-10 were best described by the Higuchi model (R2 = 0.903). ZRNE-10 displayed robust antioxidant activity (59.5 ± 1.6%) and effective inhibition of nitric oxide (76.9 ± 0.8%). It also exhibited low cytotoxicity on normal human skin fibroblasts (IC 50 ≈ 3 mg/mL). Stability assessments revealed that all ZRNE formulations maintained their physical attributes and bioactivities even after one month of storage at 25 °C, and even at an elevated temperature of 45 °C. Notably, the antioxidant activities of ZRNEs surpassed those of unencapsulated ZR extract. Given their favorable anti-inflammatory properties, low cytotoxicity, and maintained efficacy, ZRNEs hold promise as potential ingredients for topical use. [Display omitted] • ZR nanoemulsions were prepared using various hydrophilic-lipophilic balance (HLB). • The impact of HLB on the nanoemulsions' properties was emphasized. • HLB value played a critical role in drug release and cytotoxicity. • ZRNE-10 displayed excellent potential for topical anti-inflammatory applications. [ABSTRACT FROM AUTHOR]

Plutella xylostella is an important pest of brassica crops throughout the world and causes harm to family farming in the city of Bezerros in the state of Pernambuco, Brazil. The annual cost of controlling this pest surpasses 14 million dollars in northeastern Brazil. The main form of controlling this pest in these agricultural niches is the use of synthetic insecticides, such as deltamethrin, which has led to the emergence of resistant P. xylostella populations. The aim of the present study was to determine the chemical composition of essential oils from Citrus aurantium, C. limon and C. aurantiifolia and evaluate the insecticidal activity of these essential oils and selected constituents (α -terpinene, myrcene, α -pinene, ρ -cymene, β -pinene, limonene and terpinen-4-ol) on different stages of development of two populations of P. xylostella – one susceptible and one resistant to deltamethrin. A further aim was to determine the phytotoxic effects these essential oils and selected constituents on the host plant. Among the oils and chemical constituents tested, the oil from C. limon and terpinen-4-ol were the most promising and had the same level of toxicity to the populations of P. xylostella investigated. Compared to the positive controls (deltamethrin and azadirachtin), these products were more toxic and exhibited greater antifeedant action for the resistant population. Moreover, none of the oils exhibited phytotoxicity to the host plant. In conclusion, essential oils from the species of Citrus investigated and selected constituents act on different stages of development of P. xylostella (larvae and eggs) with different modes of action (larvicidal, ovicidal and antifeedant). [Display omitted] • Citrus species presented variable contents of terpenes, their main bioactive molecules. • Citrus limon essential oils showed the most relevant insecticidal activity. • Phytotoxicity bioassays showed that essential oils were not toxic to the host plant. • Chemical constituents showed toxicity different stages of development of Plutella xylostella. [ABSTRACT FROM AUTHOR]

Oxidative stress has been linked to a pathological mechanism that contributes to the initiation and progression of hepatic injury during Ichthyophthirius multifiliis infection. Thus, natural compounds with antioxidant and free radical scavenger properties, such as the Melaleuca alternifolia essential oil (TTO), might help to prevent or reduce hepatic damage. Thus, the aim of this study was to investigate whether TTO is capable of preventing or reducing hepatic oxidative damage in silver catfish naturally infected with I. multifiliis. After a TTO bath treatment of 1 h/day for 4 days, the number of trophonts on the skin of catfish was reduced by 94.87% compared to the control group. Hepatic samples from fish infected by I. multifiliis showed increased thiobarbituric acid reactive substances (TBARS) and protein carbonylation levels, while catalase (CAT) activity decreased compared to uninfected and untreated animals. Moreover, the histopathology analyses demonstrated the presence of necrosis, nuclear lateralization and cariorrexis, as well as swelling and vacuolization of cytoplasm. Treatment with TTO reduced hepatic TBARS and protein carbonylation levels and ameliorated the antioxidant system of infected fish, as well as preserve the hepatocytes morphology, but not prevented the occurrence of necrosis. Based on our findings, we propose that TTO is an alternative therapeutic option for silver catfish infected with I. multifiliis . Moreover, TTO treatment is a useful approach for avoiding or minimizing the hepatic oxidative stress caused by I. multifiliis, thus improving the hepatic antioxidant system. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the short-term tolerability of five commercially available anti-demodectic eyelid cleansers; OCuSOFT Oust Demodex (OD), I-MED I-Lid'n Lash Plus (ILL+), Labtician BlephaDex (BD), Chrissanthe Eye Cleanse (EC), and Théa Blephademodex (BDdx).Methods: Thirty healthy non-contact lens wearers (18 female; mean ± SD age, 33 ± 12 years) were enrolled in a prospective randomised crossover study. On separate visits, spaced at least 48 h apart, participants were randomised to receive topical application of one of five eyelid cleansers or saline. Participants rated subjective ocular discomfort during the 10-minute post-application period. Visual acuity, non-invasive tear film stability, conjunctival hyperaemia, and ocular surface staining were assessed at baseline and 10 min.Results: No inter-group differences in ocular parameters were noted at baseline (all p > 0.05). Ocular discomfort scores significantly exceeded baseline scores for 60 s following BD application, 120 s with OD, 135 s with BDdx, 150 s with ILL+, and 195 s with EC (all p < 0.05). Deterioration in non-invasive tear film stability, limbal conjunctival hyperaemia, as well as corneal, conjunctival, and lid margin staining was detected following EC application (all p < 0.05), and increased bulbar conjunctival hyperaemia was observed following both EC and ILL+ treatment (both p < 0.05).Conclusions: Study outcomes highlight varying tolerability profiles with different anti-demodectic lid cleanser preparations, and the potential to induce tear film instability, conjunctival hyperaemia and ocular surface staining on application. Awareness of possible adverse effects arising from topical application of commercial anti-demodectic lid cleanser formulations may help clinicians set realistic patient expectations and encourage better compliance in their use of lid hygiene therapies. [ABSTRACT FROM AUTHOR]

• The industrially – relevant product terpinen–4–ol is produced without isomers. • The synthesis proceeds with simple solid catalysts in 66% yield. • Batch and in – flow processes are both studied at multigram scale. • The synthetic three – step sequence is 100% atom economic. • Nanotitania is a competent catalyst for the isomerization of epoxides to allyl alcohols. Terpinen–4–ol is a natural product with wide application in the fragrance and agrochemical industry, currently extracted from tea tree oil or synthesized from either base–promoted rearrangement of 1,4–cineol or acid–catalyzed hydration of limonene. However, these synthetic processes, based on aggressive, unrecoverable homogeneous reagents, are non–selective and give significant amounts of isomers, which severely complicate and make more expensive the purification of the active substance. Here we show the isomers–free synthesis of terpinen–4–ol, exclusively over solid catalysts such as alumina, nanotitania and Pd/C, in >60% yield, by selective epoxidation, isomerization of terpinolene epoxide and allyl alcohol hydrogenation. The synthesis can be performed either in batch or in flow mode for the isomerization of terpinolene epoxide. The use of bare nanotitania as a selective epoxide isomerization catalyst, here demonstrated, opens new ways for the synthesis of quaternary alcohols. [Display omitted] [ABSTRACT FROM AUTHOR]

Terpinen-4-ol, the main component of Australian tea tree oil, which was widely used in pharmaceutical and cosmetic fields, was chosen as the active component in this study because of its excellent antimicrobial properties and good permeability. The objective of this study was to investigate the relationships between rheological characters, in vitro release and permeation profiles of the emulgels. Particle size distribution, optical microscopy tests were performed to characterize the status of the emulgels. Scanning electron microscopy and rheology tests were carried out to assess the strength of the structures. In vitro release and percutaneous permeation study of Terpinen-4-ol through Cellophane® membrane and excised rabbit skin were conducted by vertical Franz diffusion cell, respectively. All of the emulgel samples showed a non-uniform bimodal distribution and the microstructure represented a matrix type which could inhibit the diffusion of oil droplets in formulation in some extent. Rheological data showed a good fit to the Herschel–Bulkley model in viscosimetric studies regardless of the polymers used. Moreover, 10% Sepiplus 400 had obtained the highest zero-shear viscosity, G′, G″ value and lowest τ 95%G ′ value corresponding to the strongest structure. The results of in vitro release tests revealed that an increase in viscosity may affect the release profiles inversely, irrespective of the polymers used. In vitro permeation of Terpinen-4-ol tests indicated that when the drug amount released could satisfy the essential driving force, permeation processes was independent of release. In contrast, the drug amount released could not satisfy the essential driving force, the permeation amount was inversely proportional to the viscosity as the release amount did. [ABSTRACT FROM AUTHOR]

This work demonstrates the potential of fast multiple heart-cut enantioselective multidimensional gas chromatography (GC − e GC) and enantioselective comprehensive two-dimensional gas chromatography ( e GC × GC), to perform the stereoisomeric analysis of three key chiral monoterpenes (limonene, terpinen-4-ol and α-terpineol) present in tea tree oil (TTO). In GC − e GC, separation was conducted using a combination of mid-polar first dimension ( 1 D) column and a chiral second dimension ( 2 D) column, providing interference-free enantioresolution of the individual antipodes of each optically active component. A combination of 1 D chiral column and 2 D polar columns (ionic liquid and wax phases) were tested for the e GC × GC study. Quantification was proposed based on summation of two major modulated peaks for each antipode, displaying comparable results with those derived from GC − e GC. Fast chiral separations were achieved within 25 min for GC − e GC and < 20 min for e GC × GC, while ensuring adequate interference-free enantiomer separation. The suitability of using these two enantioselective multidimensional approaches for the routine assessment of chiral monoterpenes in TTO was evaluated and discussed. Exact enantiomeric composition of chiral markers for authentic TTOs was proposed by analysing a representative number of pure TTOs sourced directly from plantations of known provenance in Australia. Consistent enantiomeric fractions of 61.6 ± 1.5% (+):38.4 ± 1.5% (−) for limonene, 61.7 ± 1.6% (+):38.3 ± 1.6% (−) for terpinen-4-ol and 79.6 ± 1.4% (+):20.4 ± 1.4% (−) for α-terpineol were obtained for the 57 authentic Australian TTOs. The results were compared (using principle component analysis) with commercial TTOs (declared as derived from Melaleuca alternifolia ) obtained from different continents. Assessing these data to determine adulteration, or additives that affect the enantiomeric ratios, in commercially sourced TTOs is discussed. The proposed method offers distinct advantages over e GC, especially in terms of analysis times and selectivity which can serve as a reliable platform for authenticity control of TTO. [ABSTRACT FROM AUTHOR]

The growing awareness of a mounting trend toward adulteration of essential oil products has resulted in considerable interest among producer and consumer industries to develop suitable and cost-effective methods for authenticity control. In response to this trend, this study reports authenticity assessment of Australian tea tree oil (TTO) by means of stereospecific analysis of designated chiral monoterpenes present within the oil. Enantioselective gas chromatography ( e GC) coupled with either flame ionization detection or mass spectrometry was used to determine the enantiomeric distribution of terpinen-4-ol and α-terpineol, both key chemical markers in TTO. Consistent enantiomeric ratios of 68.5 ± 0.2% (+): 31.5 ± 0.2% (–) for terpinen-4-ol and 74.2 ± 1.4% (+): 25.8 ± 1.4% (–) for α-terpineol were observed for the 57 authentic 100% pure Australian TTOs analyzed, which were sourced directly from different plantation sites throughout Australia. On the other hand, considerable variations from these ratios were observed for a number of commercial TTOs sampled from different continents, with 50% of the samples varying markedly from the ∼68.5% value found for (+) terpinen-4-ol. Robustness of the method and reliability of the attained results were evaluated by cross-checking data derived from the two independent analyses performed in this study. To the best of our knowledge, this work encapsulates the most comprehensive dataset currently available for the enantiomeric distribution of terpinen-4-ol and α-terpineol in pure Australian TTO, and which can serve as an important reference for detection of variation in commercially-sourced samples, and be a potential indicator of adulteration. Additionally, results of this study proved the considerable potential of using chiral compositions of terpinen-4-ol and α-terpineol as chiral signatures for authenticity assessment of TTO. [ABSTRACT FROM AUTHOR]

[Display omitted] • Activity of four detoxifying enzymes was notably affected by terpene terpinen-4-ol. • 260 differentially expressed genes were found between T4ol-treated and control. • Pathways associated with development are inhibited following T4ol exposure. • RNAi of CYP9Z6 or GSTs7 increased mortality of T. castaneum larvae after T4ol exposure. • Terpene terpinen-4-ol exhibited pronounced contact toxicity against T. castaneum. The terpene, terpinen-4-ol (T4ol), exhibits contact toxicity in Tribolium castaneum. However, the molecular mechanisms underlying this toxicity have not been elucidated. This study examined changes in the expression of four classic enzymes after exposure of T. castaneum to T4ol. Acetylcholinesterase and glutathione S-transferase activities were markedly inhibited after exposure to T4ol, while that of the detoxifying enzyme cytochrome oxidase P450 increased markedly. Carboxylesterase activity did not show significant changes. Furthermore, RNA sequencing revealed 260 differentially expressed genes (DEG) between the T4ol-treated and control samples, and qRT-PCR was used to validate the RNA-Seq data. The Gene Ontology analysis classified the DEGs into 36 functional groups, including the immune system processes, response to stimulus, and developmental processes. T4ol altered the response to stimulus and the immune system process of beetles by inducing the expression of the genes Stabilin-1, Attacin 1, and Defensin 1. Furthermore, the DEGs receptor tyrosine kinase Torso-like protein (RTKTsl), Frizzled 4 (Fz4), Protein Wnt-5b, Ecdysone-induced protein 78C (E78), Zinc finger protein GLIS1 (ZFPGLIS1) were classified as participating in beetle development, and Fz4 and Protein Wnt-5b also mapped to the Wnt signaling pathway. This indicated that pathways associated with development are inhibited after exposure to T4ol. T4ol also induced CYP9Z6 / GSTs7 overexpression, and RNAi targeting these genes significantly increased larvae mortality on T4ol exposure, supporting the participation of CYP9Z6 / GSTs7 in the response to T4ol in T. castaneum. The results of this study will facilitate understanding of the toxic mechanisms of T4ol and provide a basis for controlling the pests of stored products. [ABSTRACT FROM AUTHOR]

Aims This study investigated the mechanisms underlying the vascular effects of terpinen-4-ol in isolated rat aortic ring preparations. Main methods The thoracic aortae of healthy rats were submitted to isometric tension recording. Membrane resting potential and input membrane resistance were measured by conventional microelectrode technique. Key findings Terpinen-4-ol reversibly relaxed endothelium-containing preparations pre-contracted with high K + and phenylephrine with IC 50 values of 421.43 μM and 802.50 μM, respectively. These effects were significantly reduced by vascular endothelium removal. In Ca 2 + -free and high K + (80 mM) medium, the contractions produced by Ba 2 + were reduced by terpinen-4-ol (100–1000 μM) in a concentration-dependent manner. In aortic rings maintained under Ca 2 + -free conditions, terpinen-4-ol significantly reduced the contractions induced by either phenylephrine (1 μM) or phorbol 12,13-dibutyrate (1 μM). Terpinen-4-ol (10–1000 μM) also relaxed the contractions evoked by BAYK-8644 (3 μM) with an IC 50 of 454.23 μM. Neither membrane resting potential nor input resistance of smooth muscle cells was altered by terpinen-4-ol exposure. Significance The present results suggest that terpinen-4-ol induced vascular smooth muscle relaxation that was preferentially due to the inhibition of electromechanical pathways related to calcium influx through voltage-operated calcium channels. [ABSTRACT FROM AUTHOR]

Abstract: The in vivo pediculicidal effectiveness of 1% and 2% formulations of tea tree (Melaleuca alternifolia) oil (TTO) against sheep chewing lice (Bovicola ovis) was tested in two pen studies. Immersion dipping of sheep shorn two weeks before treatment in both 1% and 2% formulations reduced lice to non detectable levels. No lice were found on any of the treated sheep despite careful inspection of at least 40 fleece partings per animal at 2, 6, 12 and 20 weeks after treatment. In the untreated sheep louse numbers increased from a mean (±SE) of 2.4 (±0.7) per 10cm fleece part at 2 weeks to 12.3 (±4.2) per part at 20 weeks. Treatment of sheep with 6 months wool by jetting (high pressure spraying into the fleece) reduced louse numbers by 94% in comparison to controls at two weeks after treatment with both 1% and 2% TTO formulations. At 6 and 12 weeks after treatment reductions were 94% and 91% respectively with the 1% formulation and 78% and 84% respectively with the 2% formulation. TTO treatment also appeared to reduce wool damage in infested sheep. Laboratory studies indicated that tea tree oil ‘stripped’ from solution with a progressive reduction in concentration as well as volume as more wool was dipped, indicating that reinforcement of active ingredient would be required to maintain effectiveness when large numbers of sheep are treated. The results of these studies suggest significant potential for the development of ovine lousicides incorporating TTO. [Copyright &y& Elsevier]

Abstract: Laboratory studies were conducted to assess the effect of tea tree oil (TTO) from Melaleuca alternifolia (terpinen-4-ol chemotype) against different stages of the Australian sheep blowfly Lucilia cuprina. When applied to wool, 3% TTO formulation repelled gravid female L. cuprina and prevented oviposition for six weeks. Formulations containing 1% TTO caused 100% mortality of L. cuprina eggs and 1st instar larvae and 2.5% TTO caused mortality of most second and third instar larvae in agar feeding assays. In experiments where third instar larvae were dipped in TTO formulations for 60s, concentrations of up to 50% TTO gave less than 50% kill. TTO at concentrations of 0.5%, 2% and 5% was strongly repellent to third instar larvae and caused them to evacuate treated areas. Inclusion of TTO in formulations with diazinon, ivermectin and boric acid reduced mortality in comparison with the larvicides used alone, at least partially because of avoidance behaviour stimulated by the TTO. Addition of TTO to wound treatments may aid in wound protection and myiasis resolution by preventing oviposition by L. cuprina adults, insecticidal action against L. cuprina eggs and larvae, stimulating larvae to leave the wound and through antimicrobial and anti-inflammatory properties that aid in wound healing. [Copyright &y& Elsevier]

Abstract: The aim of this study was to isolate and identify phytochemicals with anti-Helicobacter pylori activity from the stem bark of Sclerocarya birrea. The plant crude extract was fractionated by silica gel column and thin layer chromatography techniques, initially with ethyl acetate (EA) and subsequently with a combination of ethyl acetate/methanol/water (EMW). Further fractionation and identification of the phytoconstituents was achieved by gas chromatography and mass spectrometry (GC/MS) analysis. The antimicrobial activity of the fractions and compounds was evaluated against five metronidazole- and clarithromycin-resistant strains of H. pylori as well as a reference strain ATCC 43526 using the microbroth dilution technique. Amoxicillin was included in the experiments as a positive control antibiotic. Of the 18 fractions collected, 16 demonstrated anti-H. pylori activity with 50% minimum inhibitory concentration (MIC50) values ranging from 310μg/mL to 2500μg/mL. Two of the fractions (EMW fraction 6 and EA fraction 1) revealed the presence of 5 and 24 compounds, respectively, representing 40.5% and 86.57% of the total composition. Most of the compounds were essential oils, with terpinen-4-ol being the most abundant agent (35.83%), followed by pyrrolidine (32.15%), aromadendrene (13.63%) and α-gurjunene (8.77%). MIC50 ranges for amoxicillin, terpinen-4-ol and pyrrolidine were 0.0003–0.06μg/mL, 0.004–0.06μg/mL and 0.005–6.3μg/mL, respectively. The inhibitory activities of terpinen-4-ol and pyrrolidine were similar to amoxicillin (P >0.05). Most of these compounds are being reported in this plant for the first time and may represent new sources of therapeutically useful compounds against H. pylori. [Copyright &y& Elsevier]

Abstract: Pittosporum undulatum from the Azores archipelago was characterized by both molecular and volatiles analyses. Inter simple sequence repeat (ISSR) evaluation was performed based on a random sampling of 77 individuals from a total of 123 samples collected on all the Azorean islands. Molecular studies grouped the samples mainly according to the geographical collection site, with some exceptions. Leaf volatiles were isolated by distillation–extraction and analyzed by gas chromatography (GC) and gas chromatography–mass spectrometry (GC–MS) from all the 123 samples. Cluster analysis based on the leaf volatiles chemical composition defined three main clusters, not related to sample site collection, and was based mainly on the relative amounts of limonene (3–89%), sabinene (0.1–64%) and terpinen-4-ol (traces-43%). Clusters obtained from both molecular studies and volatiles composition were not superimposable and no correlation between ISSR markers and volatile oils could be drawn. The results suggest that there is a high genetic variability among individuals of P. undulatum that can explain the invasive ability of this species in the Azores archipelago. The detailed characterization of this alien weed species may assist finding potential commercial uses as well as management strategies to help its eradication and/or control. [Copyright &y& Elsevier]

Abstract: The dried fruits of Zanthoxylum rhesta DC syn Z. budrungawall syn. Z. limonella (Dennst) are used as condiments and have spice value. While the essential oil is concentrated in the pericarp, the seeds have fatty oil. The extraction of fragrance/flavour components is carried out from the pericarp by subcritical CO2, modified methanol–subcritical CO2, hydrodistillation and traditional solvent extraction processes and the composition of these extracts are compared. The components are identified by GC–MS and the composition is determined by GC–FID. The principal components such as sabinene, terpinen-4-ol, α-terpineol are present in different amounts in the extracts. The traditional solvent extraction processes provide more amounts of waxy components along with the principal components. Though hydrodistillation process provides a wax free essential oil, the yield is low. The extract obtained by the subcritical CO2 method is superior in comparison to traditional processes, but it contains higher percentage of monoterpenes in comparison to oxygenated monoterpenes. On the other hand, extraction of all the desired components is possible through pre-treatment of pericarp by small amounts of methanol. These details are described and discussed. [Copyright &y& Elsevier]

Abstract: Essential oils are widely used in pharmaceutical and cosmetic preparations e.g. as fragrance, active ingredient or penetration enhancer. However, reports on skin absorption are rare. Therefore, the aim of our study was to investigate the capability of terpinen-4-ol, the main compound of Australian tea tree oil (TTO), to permeate human skin. In static Franz diffusion cells permeation experiments with heat separated human epidermis were carried out using infinite dosing conditions and compared to liberation experiments. The flux values of three different semisolid preparations with 5% TTO showed the rank order semisolid O/W emulsion (0.067μl/cm2 h)>white petrolatum (0.051μl/cm2 h)>ambiphilic cream (0.022μl/cm2 h). In comparison to the flux value obtained with the native TTO (0.26μl/cm2 h), the flux values are remarkably reduced due to the lower amount of terpinen-4-ol. P app values for cream (2.74±0.06×10−7 cm/s) and native TTO (1.62±0.12×10−7 cm/s) are comparable whereas white petrolatum (6.36±0.21×10−7 cm/s) and semisolid O/W emulsion (8.41±0.15×10−7 cm/s) demonstrated higher values indicating a penetration enhancement. No relationship between permeation and liberation was found. [Copyright &y& Elsevier]

Abstract: The essential oils of aerial parts of three Artemisia species (A. absinthium, A. santonicum and A. spicigera) were isolated by hydrodistillation method and tested for their toxicity against to granary weevil, Sitophilus granarius (L.) (Coleoptera: Curculionidae). All of the essential oils tested were found to be toxic to adults of S. granarius. The oils showed about 80–90% mortality of granary weevil, S. granarius at a dose of 9μl/l air after 48h of exposure. The constituents of these oils isolated from Artemisia spp. were also analyzed by GC–MS method. Camphor, 1,8-cineole, chamazulene, nuciferol propionate, nuciferol butanoate, caryophyllene oxide, terpinen-4-ol, borneol and α-terpineol were the predominant components of the oils. Some pure compounds (camphor, 1,8-cineole, terpinen-4-ol, borneol, bornyl acetate and α-terpineol) identified as major component in the oils, at 0.5, 0.75 and 1μl/l air doses were also tested for their toxicity against S. granarius. While all pure compounds were found to be toxic against S. granarius, 1,8-cineole and terpinen-4-ol were more toxic among the tested pure compounds. 1,8-Cineole and terpinen-4-ol showed 100% mortality at all doses after 12h of exposure. It can be concluded that essential oils of three Artemisia species and their major components, 1,8-cineole and terpinen-4-ol are potential control agents against S. granarius. [Copyright &y& Elsevier]

Abstract: A HPTLC method has been developed and validated for the determination of tea tree oil from cosmeceutical formulations. Tea tree oil concentration was estimated by analyzing the terpinen-4-ol content. The method employed TLC aluminium plates precoated with silica gel 60F-254. The solvent system consisted of toluene and ethyl acetate in the ratio 85:15. The calibration curve of terpinen-4-ol was linear in the range of 100–900ng. The polynomial regression data for the calibration plots showed a good linear relationship with r 2 =0.9949. The Rf value of terpinen-4-ol was found to be 0.62±0.05. The method was validated for precision and accuracy. The minimum detectable amount was found to be 60ng. The limit of quantitation was found to be 100ng. The drug content was within the limits (±5% of the labeled content of the formulations). The recovery of tea tree oil was greater than 99%. The method was found to be simple, sensitive, precise, accurate and specific for estimation of tea tree oil from formulations. [Copyright &y& Elsevier]

Individual leaves of the three most common chemotypes of Melaleuca alternifolia were examined both quantitatively and qualitatively for volatile constituents from the emergence of the first true leaves, through to 6-week-old tenth leaf set material. The 1,8-cineole and terpinolene chemotypes were investigated and compared with the recently reported commercial terpinen-4-ol chemotype. The 1,8-cineole chemotype was found to accumulate 1,8-cineole and associated p-menthanes limonene, terpinen-4-ol and α-terpineol gradually with increasing leaf set number. As with the terpinen-4-ol variety, higher than expected concentrations of the pinenes and terpinolene were found only in the early leaf sets. The terpinolene variety showed two stages of terpinolene accumulation, the first at leaf sets 2–3 similar to the unexpected biosynthesis of terpinolene in the terpinen-4-ol chemotype and the second at leaf sets 8–9 which is characteristic of the terpinolene variety. [Copyright &y& Elsevier]

In recent decades, Melaleuca alternifolia has been grown in plantations for the commercial production of tea tree oil extracted from harvested leaf and stem material by steam distillation. Plantations are grown from seedlings raised from seeds collected from wild populations of this endemic Australian species. Considerable variation in morphology and leaf oil composition and yield has been observed and studies have demonstrated genetic and phenotypic heterozygosity between populations.Here we examine the variation in leaf oil chemical composition (chemotypes) between geographically defined locations of wild populations of M. alternifolia and investigate the relationships between tree size, chemotype and geographic location.Forty separate populations of M. alternifolia distributed amongst three river catchments (two in a warm moist coastal region and one in cool drier highlands) were studied. Total variation in tree size was significantly greater within individual sites than between them. However, the highland catchment populations exhibited significantly smaller mean tree size and a significantly different chemotype profile than the lowland populations. Contrary to the observation of lower genetic diversity, the highland catchment populations had greater chemotypic diversity. Furthermore, highly significant differences in population chemotypes were demonstrated between catchments.The possibilities that these differences could be ascribed to either genetic divergence or to environmental differences are discussed. [Copyright &y& Elsevier]

Individual leaves of the commercial terpinen-4-ol type of Melaleuca alternifolia were examined both quantitatively and qualitatively for volatile constituents from the emergence of the first true leaves, through to 6-week-old tenth leaf set material. A GC internal standard addition method was used to measure changes in oil composition and the accumulation of volatile constituents expressed on a dry weight, unit leaf area and whole leaf basis. In the early stages of seedling growth, leaves contained higher concentrations of terpinolene, α-pinene and β-pinene and lower concentrations of terpinen-4-ol, sabinene and cis-sabinene hydrate than mature leaf. Concentrations of the former constituents fell and the latter rose by the time leaf set 10 was 6 weeks old. Key constituent, 1,8-cineole remained in similar concentration throughout ontogeny. The variation in concentration of other key constituents during early stages of seedling development suggests that caution is required in extrapolating seedling leaf data to mature tree oil quality. [Copyright &y& Elsevier]

• NMR shows higher levels of sucrose and fructose in terpinen-4-ol-treated strawberry. • Lower levels of α- d -glucose, β- d -glucose, and citric acid in treated fruit by NMR. • Higher anthocyanin content in terpinen-4-ol treated fruit. • Terpinen-4-ol increases the gene expression of sucrose and anthocyanin synthesis. • Higher sucrose levels induce anthocyanin accumulation in terpinen-4-ol treated fruit. Terpinen-4-ol, the main component of tea tree oil, controls postharvest decay of strawberry fruit. In this study, nuclear magnetic resonance (NMR)-based metabolomics was used to investigate global metabolic profiles in strawberries treated with terpinen-4-ol and stored at 20 °C for 3 d. Measurements showed higher levels of sucrose and fructose, and lower levels of α- d -glucose, β- d -glucose, and citric acid in terpinen-4-ol-treated fruit. Treatment also increased expression of FaSS and FaSPS mRNAs and decreased expression of FaAI. Terpinen-4-ol treatment maintained higher anthocyanin levels accompanied by increasing the expression of genes in the pentose phosphate, phenylpropanoid, and flavonoid pathways, and transcription factor MYB10. In addition, expression of FaSnRK1 was also increased in terpinen-4-ol-treated fruit. We conclude that terpinen-4-ol maintains strawberry fruit quality by regulating sucrose metabolism and anthocyanin biosynthesis, and that FaSnRK1 perceives the higher sucrose levels to induce anthocyanin accumulation in treated fruit. [ABSTRACT FROM AUTHOR]

Abstract: Widdringtonia is the only genus of the 16 genera of Cupressaceae present in South Africa. This genus is represented by three species in South Africa; W. nodiflora, W. schwarzii and W. cedarbergensis (= W. juniperoides) and the latter listed as critically endangered. Cedarwood oil (generally obtained from Juniperus species) is widely used as a fragrance material in several consumer products, however, no data has been published on the volatiles of the Clanwilliam cedar (W. cedarbergensis) native to South Africa. The essential oil composition of the wood and leaf oil isolated by hydro-distillation were analysed by GC–MS. The two oils were distinctly different. Twenty compounds representing 93.8% of the total oil were identified in the leaf oil which was dominated by terpinen-4-ol (36.0%), sabinene (19.2%), γ-terpinene (10.4%), α-terpinene (5.5%) and myrcene (5.5%). Twenty six compounds representing 89.5% of the total were identified in the wood oil with the predominance of thujopsene (47.1%), α-cedrol (10.7%), widdrol (8.5%) and cuparene (4.0%). [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the sedative and anesthetic potential of the essential oil (PHEO) and hydrolate (PHH) from the fruit of Protium heptaphyllum and the isolated compounds (IC) of PHEO in tambaqui (Colossoma macropomum) juveniles. Fish were placed in aquaria with different concentrations of PHEO, PHH or IC (sabinene, terpinen-04-ol, γ-terpinene and α-pinene) to evaluate sedative and anesthetic efficacy. In another experiment, fish were transported for 22 h with 10% anesthetic concentrations added to the water of transport. No similarities regarding the major compounds of PHEO and PHH were observed. No mortality was observed during the experiments, and PHH did not show any sedative or anesthetic effect. PHEO induced sedation at 250 mg L−1 and deep anesthesia at 500, 750 and 1000 mg L−1. The recovery time increased with increasing concentration of PHEO. There was a significant difference in the time to induce deep anesthesia between PHEO and IC. Water conductivity and mucous cell density were lower in the transport with 50 mg L−1 PHEO. Tambaqui transported with 50 mg L−1 PHEO and 11.6, 17.4, and 23.2 mg L−1 terpinen-04-ol presented lower net whole body K+ and Cl− effluxes. PHEO is an alternative as sedative and anesthetic for tambaqui juveniles, and the concentration of 500 mg L−1 was the best for deep anesthesia. The use of 50 mg L−1 PHEO was effective for the transport of this species because it reduced net K+ and Cl− effluxes and did not stimulate proliferation mucous cells. • Protium heptaphyllum essential oil is effective to sedate /anesthetize Tambaqui. • All isolated compounds showed sedative or anesthetic activity. • Essential oil affects the osmoregulatory system during long-time transportation. • The mucous cells of fish transported with the essential oil were not stimulated. [ABSTRACT FROM AUTHOR]

• CARAS is a serious health problem all over the world generating negative economic and social impacts. • 4-carvomenthenol (Carvo), an essential oil, reduces airway mucus production. • Carvo is a potent immunomodulatory molecule by decreasing IL-13 and increasing IL-10 into the airway. • The mechanism of action of Carvo is related, at least, with the p38MAPK / NF-κB (p65) signaling pathway inhibition. The aim of this study was to analyze the 4-carvomenthenol (carvo) oral treatment on the experimental model of the combined allergic rhinitis and asthma syndrome (CARAS). BALB/c mice were OVA-sensitized on day zero and 7th (50 μg/mL OVA in 10 mg/mL Al (OH)3) and OVA-challenged (5 mg/mL, 20 μL/animal) for three weeks. In the last week, the animals were dally challenged with aerosol of OVA and the carvo treatment (12.5, 25 or 50 mg/kg) occurred one hour before each OVA-challenge. Data were analyzed and p < 0.05 was considered significant. Carvo (12.5–50 mg/kg) decreased significantly the eosinophil migration into the nasal (NALF) and bronchoalveolar (BALF) cavities as well as on the nasal and lung tissues of sick animals. The treatment also decreased mucus production on both tissue sections stained with PAS (periodic acid-Schiff satin). In addition, the histological analyzes demonstrated that sick mice presented hyperplasia and hypertrophy of the lung smooth muscle layer followed by increasing of extracellular matrix and carvo (50 mg/kg) inhibited these asthmatic parameters. We analyzed the allergic rhinitis signals as nasal frictions and sneezing and observed that carvo decreased these two signals as well as serum OVA-specific IgE titer, type 2 cytokine synthesis, mainly IL-13, with increasing of IL-10 production. Decreasing of IL-13 production corroborated with decreasing of mucus production and these effects were dependent on p38MAPK/NF-κB(p65) signaling pathway inhibition. Therefore, these data demonstrated that a monoterpene of essential oils presents anti-allergic property on an experimental model of CARAS suggesting a new drug prototype to treat this allergic syndrome. [ABSTRACT FROM AUTHOR]

Oil quantity and quality were measured for the cotyledon leaves of the commercial terpinen-4-ol chemical variety of Melaleuca alternifolia. Oil yield obtained by ethanolic extraction was 3.8 micrograms per leaf or 2.6% (dry weight basis). The major components of the oil were α-pinene (7.4%), β-pinene (12.0%) and terpinolene (27.3%). The non-commercial terpinolene chemical variety was found to be rich in 1,8-cineole (12.5%) and terpinolene (25.4%). The non-commercial 1,8-cineole chemical variety was rich in 1,8-cineole (37%) with significant quantities of α-pinene (15.5%), β-pinene (23.3%) and terpinolene (10.9%). The cotyledon leaf composition, when compared with that of mature leaf from the same chemical variety, was found to be biased toward pinene and terpinolene biogenetic pathway constituents and hence not a good indicator of mature tree quality especially for the commercial terpinen-4-ol chemical variety. The implications of these analyses for the determination of M. alternifolia plantation quality and the understanding of oil formation, are discussed. [Copyright &y& Elsevier]

The monoterpenoid terpinen-4-ol (4TERP) is known to inhibit cell excitability, has low toxicity and important pharmacological activities, which are likely related to neural excitability, such as anti-inflammatory, antiepileptic and antinociceptive effects. However, the pharmacological characteristics and mechanisms underlying the effects of 4TERP on blockade of neural action potential are not completely elucidated. Since Na+ current (I Na) through voltage-dependent Na+ channels (Na V) is a major mechanism for excitability, the present study investigated the pharmacological characteristics and mechanisms of the action of 4TERP on I Na through Na V. For this aim, dissociated small neurons of dorsal root ganglia of adult rats were used for whole cell patch-clamp recordings. 4TERP concentration-dependently inhibits I Na (IC 50 0.8 ± 0.3 mM; pharmacological efficacy 42.89 ± 5.54%). 4TERP interfered with I Na through a mechanism with various components, which includes predominantly channel pore block and sensitivity to frequency of use. In presence of 4TERP (3 mM), decreasing stimulation from 5 Hz to very low frequency (75 s of quiescence previously to stimulation) induced I Na decrease to 65.17 ± 5.86% of control. 4TERP also altered (left shift) voltage sensitivity of the steady state activation of Na V. Data are discussed aiming to interpret the importance of blockade of I Na through Na V as participant of 4TERP-induced inhibition of membrane excitability. • 4TERP concentration-dependently inhibits voltage-dependent Na+ channels activation. • 4TERP inhibits I Na predominantly through the mechanism of channel pore blockade. • 4TERP blockade showed sensitivity to use-dependence. • This effect is coherent with 4TERP-induced blockade of neuronal excitability. [ABSTRACT FROM AUTHOR]

Abstract: This note summarises recent studies on skin penetration of terpinen-4-ol, which is the main component of tea tree oil [S.E. Cross, M. Russell, I. Southwell, M.S. Roberts, Human skin penetration of the major components of Australian tea tree oil applied in its pure form and as a 20% solution in vitro, Eur. J. Pharm. Biopharm. doi: 10.1016/j.ejpb.2007.10.002 (in press)]. The influence of different experimental models on obtained skin penetration results is discussed. [Copyright &y& Elsevier]