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The present study investigates the wound healing potential of three chitosan-based topical preparations loaded with either tea tree essential oil, rosemary essential oil or a mixture of both oils in vivo. Essential oils of M. alternifolia and R. officinalis were analyzed using GC/MS. Essential oil-loaded chitosan topical preparations were formulated. Wound healing potential was evaluated in vivo using an excision wound model in rats. GC/MS analysis of M. alternifolia and R. officinalis essential oils revealed richness in oxygenated monoterpenes, representing 51.06% and 69.61% of the total oil composition, respectively. Topical application of chitosan-based formulation loaded with a mixture of tea tree and rosemary oils resulted in a significant increase in wound contraction percentage compared to either group treated with individual essential oils and the untreated group. Histopathological examination revealed that topical application of tea tree and rosemary oil combination demonstrated complete re-epithelialization associated with activated hair follicles. The high percentage of oxygenated monoterpenes in both essential oils play an important role in the antioxidant and wound healing potential observed herein. Incorporation of tea tree and rosemary essential oils in chitosan-based preparations in appropriate combination could efficiently promote different stages of wound healing.

Tea tree oil (TTO) is a yellow liquid extracted from Melaleuca alternifolia . Although the antimicrobial activity of TTO has been known for a long time, its specific antimicrobial effects and mechanism underlying these remain poorly characterized. The present study investigated the chemical composition of TTO and the dynamics and mechanism of its antimicrobial activities in two bacterial and two fungal strains. Gas chromatography–mass spectrometry analysis identified alkenes and alcohols as the main constituents of TTO. Terpinen-4-ol was the most abundant individual component, accounting for approximately 23 % of the TTO. Poisoned food technique assessment showed that the minimum inhibitory concentrations of TTO for bacterial strains ( Escherichia coli and Staphylococcus aureus ) and fungal strains ( Candida albicans and Aspergillus niger ) were 1.08 and 2.17 mg/mL, respectively. Antimicrobial dynamic curves showed that with increasing concentrations of TTO, the rate of cell killing and the duration of growth lag phase increased correspondingly. These data indicated that TTO produced concentration and time-dependent antimicrobial effects. The minimum bactericidal and fungicidal concentrations of TTO were 2.17, 4.34, and 4.34 against E. coli , S. aureus , and C. albicans , respectively. However, A. niger conidia were not completely eradicated, even after 3 days in the presence of 17.34 mg/mL TTO. Transmission electron microscopy images indicated that TTO penetrated the cell wall and cytoplasmic membrane of all the tested bacterial and fungal strains. TTO may also penetrate fungal organelle membrane. These findings indicated that TTO maybe exerts its antimicrobial effects by compromising the cell membrane, resulting in loss of the cytoplasm and organelle damage, which ultimate leads to cell death.

Background: Finding an effective treatment for acne that is well tolerated by the patients is a challenge. One study has suggested the efficacy of tea tree oil in treatment of the acne vulgaris. Aim: To determine the efficacy of tea tree oil in mild to moderate acne vulgaris. Methods: This was a randomized double-blind clinical trial performed in 60 patients with mild to moderate acne vulgaris. They were randomly divided into two groups and were treated with tea tree oil gel (n=30) or placebo (n=30). They were followed every 15 days for a period of 45 days. Response to treatment was evaluated by the total acne lesions counting (TLC) and acne severity index (ASI). The data was analyzed statistically using t-test and by SPSS program. Results: There were no significant differences regarding demographic characteristics between the two groups. There was a significant difference between tea tree oil gel and placebo in the improvement of the TLC and also regarding improvement of the ASI. In terms of TLC and ASI, tea tree oil gel was 3.55 times and 5.75 times more effective than placebo respectively. Side-effects with both groups were relatively similar and tolerable. Conclusion: Topical 5% tea tree oil is an effective treatment for mild to moderate acne vulgaris.

Background The gold standard in treatment of periodontitis is mechanical removing of dental biofilm but using local delivery drugs as adjunctive to SRP is widely used to modulate inflammatory host and eradicate microbes. Tea tree oil (TTO) has a broad-spectrum antimicrobial, anti-inflammatory, antifungal, antiviral, antioxidant effect. This study aimed to assess clinically and biochemically the effect of intrapocket application of TTO ( Melaleuca alternifolia ) gel adjunctive to scaling and root planing (SRP) in the treatment of stage 2 (moderate) periodontitis and to correlate the biochemical levels with clinical response. Methods A randomized, controlled clinical trial was conducted on thirty patients with stage 2 periodontitis. Patients were equally divided into two groups: Control Group treated with (SRP) alone and Test Group treated with SRP and locally delivered 5% TTO gel. Clinical assessment included pocket probing depth (PPD), clinical attachment loss (CAL), gingival index (GI) and bleeding on probing (BOP) measured at baseline and after 3 and 6 months. The level of matrix metalloproteinase-8 (MMP-8), in the gingival crevicular fluid (GCF) was also assessed at baseline and after1, 3 and 6 months by Enzyme-linked immunosorbent assay (ELISA) kit. Chi-square, Student t- tests, Mann–Whitney U test and Spearman correlation were the statistical tests used in the study. Results An improvement of all clinical and biochemical parameters was observed (at p  < 0.001) in both groups. A significant difference between the two groups was found in both clinical and biochemical parameters. Conclusion The local delivery of TTO gel adjunctive to SRP proved to be effective in the treatment of stage II periodontitis. Trial registration The study was retrospectively registered at clinicaltrials.gov NCT04769271, on 24/2/2021.

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.

Australian tea tree oil (TTO) and its extract terpinen-4-ol (T4O) are found to be effective in moderating demodex-related diseases. Their possible effects are lowering the mite counts, relieving the demodex-related symptoms and modulating the immune system especially the inflammatory response. This review summarizes the topical treatments of TTO and T4O in human demodicosis, their possible mechanism of actions, side-effects and potential resistance in treating this condition. Although current treatments other than TTO and T4O are relatively effective in controlling the demodex mite population and the related symptoms, more research on the efficacy and drug delivery technology is needed in order to assess its potential as an alternative treatment with minimal side-effect profile, low toxicity and low risk of demodex resistance.

In this study, antibacterial and antioxidant molecules-rich Melaleuca alternifolia oil (tea tree oil (TTO)) loaded chitosan (CS) based nanoemulsions (NEMs) were prepared and encapsulated by sodium alginate (SA) microsphere for antibacterial wound dressing. CS-TTO NEMs were prepared by oil-in-water emulsion technique, and the nanoparticle tracking analysis (NTA) confirmed that the CS-TTO NEMs had an average particle size of 89.5 nm. Further, the SA-CS-TTO microsphere was confirmed through SEM analysis with an average particle size of 0.76 ± 0.10 µm. The existence of TTO in CS NEMs and SA encapsulation was evidenced through FTIR analysis. The XRD spectrum proved the load of TTO and SA encapsulation with CS significantly decreased the crystalline properties of the CS-TTO and SA-CS-TTO microsphere. The stability of TTO was increased by the copolymer complex, as confirmed through thermal gravimetric analysis (TGA). Furthermore, TTO was released from the CS–SA complex in a sustained manner and significantly inhibited the bacterial pathogens observed under confocal laser scanning microscopy (CLSM). In addition, CS-TTO (100 µg/mL) showed antioxidant potential (>80%), thereby increasing the DPPH and ABTS free radicals scavenging ability of SA-CS-TTO microspheres. Moreover, CS and SA-CS-TTO microsphere exhibited negligible cytotoxicity and augmented the NIH3T3 cell proliferation confirmed in the in vitro scratch assay. This study concluded that the SA-CS-TTO microsphere could be an antibacterial and antioxidant wound dressing.

Over the past 20–30 years, Trichophyton rubrum represented the most widespread dermatophyte with a prevalence accounting for 70% of dermatophytosis. The treatment for cutaneous infections caused by Trichophyton spp. are imidazoles (ketoconazole (KTZ)) and triazoles (itraconazole (ITZ)). T. rubrum can develop resistance to azoles after prolonged exposure to subinhibitory concentrations resulting in therapeutic failures and chronic infections. These problems have stimulated the search for therapeutic alternatives, including essential oils, and their potential use in combination with conventional antifungals. The purpose of this study was to evaluate the antifungal activity of tea tree oil (TTO) (Melaleuca alternifolia essential oil) and the main components against T. rubrum and to assess whether TTO in association with KTZ/ITZ as reference drugs improves the antifungal activity of these drugs. We used a terpinen-4-ol chemotype (35.88%) TTO, and its antifungal properties were evaluated by minimum inhibitory and minimum fungicidal concentrations in accordance with the CLSI guidelines. The interaction between TTO and azoles was evaluated through the checkerboard and isobologram methods. The results demonstrated both the fungicide activity of TTO on T. rubrum and the synergism when it was used in combination with azoles. Therefore, this mixture may reduce the minimum effective dose of azole required and minimize the side effects of the therapy. Synergy activity offered a promise for combination topical treatment for superficial mycoses.

Fungal skin infections are currently a major clinical problem due to their increased occurrence and drug resistance. The treatment of fungal skin infections is based on monotherapy or polytherapy using the synergy of the therapeutic substances. Tea tree oil (TTO) may be a valuable addition to the traditional antifungal drugs due to its antifungal and anti-inflammatory activity. Ketoconazole (KTZ) is an imidazole antifungal agent commonly used as a treatment for dermatological fungal infections. The use of hydrogels and organogel-based formulations has been increasing for the past few years, due to the easy method of preparation and long-term stability of the product. Therefore, the purpose of this study was to design and characterize different types of Pluronic® F-127 gel formulations containing KTZ and TTO as local delivery systems that can be applied in cases of skin fungal infections. The influence of TTO addition on the textural, rheological, and bioadhesive properties of the designed formulations was examined. Moreover, the in vitro release of KTZ, its permeation through artificial skin, and antifungal activity by the agar diffusion method were performed. It was found that obtained gel formulations were non-Newtonian systems, showing a shear-thinning behaviour and thixotropic properties with adequate textural features such as hardness, compressibility, and adhesiveness. Furthermore, the designed preparations with TTO were characterized by beneficial bioadhesive properties. The presence of TTO improved the penetration and retention of KTZ through the artificial skin membrane and this effect was particularly visible in hydrogel formulation. The developed gels containing TTO can be considered as favourable formulations in terms of drug release and antifungal activity.

Nanoemulsion is a new multi-component drug delivery system; the selection of different oil phases can give it special physiological activity, and play the role of “medicine and pharmaceutical excipients all-in-one”. In this paper, we used glycyrrhizic acid as the natural surfactant, and Blumea balsamifera oil (BB) and tea tree oil (TTO) as the mixed oil phase, to obtain a new green functional composite nanoemulsion. Using the average particle size and polydispersion index (PDI) as the evaluation criteria, the effects of the oil ratio, oil content, glycyrrhizic acid concentration, and ultrasonic time on the nanoemulsion were systematically investigated. The stability and physicochemical properties and biological activities of BB-TTO NEs prepared via the optimum formulation were characterized. The optimal prescription was BB: TTO = 1:1, 5% oil phase, 0.7% glycyrrhizic acid, and 5 min ultrasonication time. The mean particle size, PDI, and zeta potential were 160.01 nm, 0.125, and −50.94 mV, respectively. The nanoemulsion showed non-significant changes in stability after centrifugation, dilution, and 120 days storage. These nanoemulsions were found to exhibit potential antibacterial and anti-inflammatory activities. The minimal inhibitory concentration (MIC) of BB-TTO NEs against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa is 2975 μg/mL, 2975 μg/mL, and 5950 μg/mL, respectively. A lower level of inflammatory cell infiltration and proportion of fibrosis were found in the synovial tissue of AIA rats treated with BB-TTO NEs. These findings demonstrate that the BB-TTO NEs produced in this study have significant potential for usage in antibacterial and anti-inflammatory areas.