Thymol and carvacrol are phenolic monoterpenes found in thyme, oregano, and several other species of the Lamiaceae. Long valued for their smell and taste, these substances also have antibacterial and ...anti-spasmolytic properties. They are also suggested to be precursors of thymohydroquinone and thymoquinone, monoterpenes with anti-inflammatory, antioxidant, and antitumor activities. Thymol and carvacrol biosynthesis has been proposed to proceed by the cyclization of geranyl diphosphate to γ-terpinene, followed by a series of oxidations via
-cymene. Here, we show that γ-terpinene is oxidized by cytochrome P450 monooxygenases (P450s) of the CYP71D subfamily to produce unstable cyclohexadienol intermediates, which are then dehydrogenated by a short-chain dehydrogenase/reductase (SDR) to the corresponding ketones. The subsequent formation of the aromatic compounds occurs via keto-enol tautomerisms. Combining these enzymes with γ-terpinene in in vitro assays or in vivo in
yielded thymol and carvacrol as products. In the absence of the SDRs, only
-cymene was formed by rearrangement of the cyclohexadienol intermediates. The nature of these unstable intermediates was inferred from reactions with the γ-terpinene isomer limonene and by analogy to reactions catalyzed by related enzymes. We also identified and characterized two P450s of the CYP76S and CYP736A subfamilies that catalyze the hydroxylation of thymol and carvacrol to thymohydroquinone when heterologously expressed in yeast and
Our findings alter previous views of thymol and carvacrol formation, identify the enzymes involved in the biosynthesis of these phenolic monoterpenes and thymohydroquinone in the Lamiaceae, and provide targets for metabolic engineering of high-value terpenes in plants.
•SPI can easily form nanocomplexes with thymol.•The water solubility and stability of thymol was enhanced by nanocomplexation with SPI.•The antimicrobial activities of thymol against E. coli and S. ...aureus were improved by nanocomplexation with SPI.
The complexation of thymol with soy protein isolate (SPI) at various mixing mass ratios, as well as some physicochemical characteristics, stability and antibacterial properties of the resultant complexes, was evaluated. The loading capacity of thymol in complexes formed at a mixing mass ratio of 2.5:12 was 10.36%, and the particles were spherical with a z-average diameter less than 110 nm. Fluorescence spectroscopy results indicated the SPI-thymol nanocomplexes were formed mainly through hydrophobic interactions. Upon nanocomplexation, the solubility, sustained release, thermal stability and antibacterial activity of thymol were greatly improved. Moreover, the encapsulation efficiency and solubility of thymol in complexes were improved with the increasing mixing mass ratio, while the stability and antibacterial activity of thymol were not significantly different among all the complexes. These findings suggest that SPI could be used as a nanocarrier for improving solubility and stability of thymol.
An antibacterial and plant growth promoting nanoemulsion was formulated using thymol, an essential oil component of plant and Quillaja saponin, a glycoside surfactant of Quillaja tree. The emulsion ...was prepared by a sonication method. Fifty minutes of sonication delivered a long term stable thymol nanoemulsion which was characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), cryogenic-field emission scanning electron microscopy (Cryo-FESEM) and fourier transform infra-red (FTIR) spectroscopy. Creaming index, pH and dilution stability were also studied for deliberation of its practical applications. The nanoemulsion (0.01-0.06%, v/v) showed substantial in vitro growth inhibition of Xanthomonas axonopodis pv. glycine of soybean (6.7-0.0 log CFU/ml). In pot experiments, seed treatment and foliar application of the nanoemulsion (0.03-0.06%, v/v) significantly lowered the disease severity (DS) (33.3-3.3%) and increased percent efficacy of disease control (PEDC) (54.9-95.4%) of bacterial pustule in soybean caused by X. axonopodis pv. glycine. Subsequently, significant enhancements of plant growth were also recorded in plants treated with thymol nanoemulsion. This is the first report of a thymol based nanoemulsion obtained using Quillaja saponin as a surfactant. Our study claims that nano scale thymol could be a potential antimicrobial and plant growth promoting agent for agriculture.
Pathogenic microorganisms posed perniciousness for postharvest fruits and vegetables, as well as brought potential risks for human health. In this work, pullulan/polyvinyl alcohol (PUL/PVA) ...nanofibers incorporated with thymol-loaded porphyrin metal-organic framework nanoparticles (THY@PCN-224 NPs) were developed for antibacterial food packaging. PCN-224 MOFs not only act as thymol loading carriers but also highly produce singlet oxygen (1O2) with bactericidal activity. PUL/PVA nanofiber was a promising sustainable substrate because of its good flexibility, biocompatibility and biodegradability. The loading capacity of PCN-224 for thymol was about 20%. The THY@PCN/PUL/PVA nanofibers exhibited synergistic antibacterial activities against E. coli (~99%) and S. aureus (~98%) under light irradiation. The cell viability assays and fruit preservation study demonstrated good biosafety of the polymeric film. The results suggested that this novel nanofiber has potential application prospects for food packaging.
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•Pullulan/polyvinyl alcohol (PUL/PVA) biopolymer nanofibers were fabricated.•PUL/PVA nanofibers showed good availability, biodegradability and biosafety.•PCN-224 has photosensitive bactericidal activity under light irradiation.•Thymol loaded into PCN-224 nanoparticles achieved synergistic antibacterial activity.•Polymer-based THY@PCN@PUL/PVA nanofibers have potential in active packaging.
Thymol (a phenol ring bearing active phytoconstituent) is a privileged scaffold, which is diversified in natural sources. This scaffold acts as an obligatory template for scheming and arriving at ...designing some newer drug‐molecules with potential biological activities. In the pharmacological perspective, the promising active sites of the scaffold are the positions C‐1, C‐4, and C‐6 of thymol that would be accountable for developing potent drug candidates. This review aims to explore the various synthetic routes and the structural‐activity relationship of thymol scaffold with suitable active pharmacophore sites.
•ZnO-NPs affect fish health by inducing various toxic traits, including cytotoxicity, genotoxicity, and embryotoxicity.•Thymol has been successfully used in fish nutrition to enhance nutrient ...bioavailability and growth performance.•Thymol protected against ZnO-NPs-induced immunotoxicity in fish co-supplemented with thymol.•The exposed fish to ZnO-NPs revealed a decline in serum immunoglobulins, nitric oxide, and the activities of lysozyme and myeloperoxidase.
Zinc oxide nanoparticles (ZnO-NPs) have many exciting properties that make their use in a continuous increase in various biomedical, industrial, and agricultural applications. This is associated with accumulation in the aquatic ecosystems and fish exposure with consequent deleterious effects. To determine the potential of thymol to counteract the immunotoxic effects of ZnO-NPs, Oreochromis niloticus was exposed to ZnO-NPs (⅕ LC50 =1.14 mg/L, for 28 days) with or without feeding a thymol-incorporated diet (1 or 2 g/kg diet). Our data demonstrated a reduction of aquaria water quality, leukopenia, and lymphopenia with a decrease in serum total protein, albumin, and globulin levels in exposed fish. At the same time, the stress indices (cortisol and glucose) were elevated in response to ZnO-NPs exposure. The exposed fish also revealed a decline in serum immunoglobulins, nitric oxide, and the activities of lysozyme and myeloperoxidase, in addition to reduced resistance to the Aeromonas hydrophila challenge. The RT-PCR analysis showed downregulation of antioxidant (SOD) superoxide dismutase and (CAT) catalase gene expression in the liver tissue with overexpression of the immune-related genes (TNF-α and IL-1β). Importantly, we found that thymol markedly protected against ZnO-NPs-induced immunotoxicity in fish co-supplemented with thymol (1 or 2 g/kg diet) in a dose-dependent manner. Our data confirm the immunoprotective and antibacterial effects of thymol in ZnO-NPs exposed fish, supporting the potential utility of thymol as a possible immunostimulant agent.
Essential oils are natural antimicrobils and have been frequently incorporated into edible films aimed at extending shelf-life of food products. In this study, thymol nanoemulsions co-emulsified by ...natural emulsifiers (i.e., blend of gelatin and soy lecithin) were prepared and incorporated into gelatin films. The physical and antimicrobial properties of gelatin films were characterized. Thymol nanoemulsions incorporation increased the water vapor permeability and elongation at break of gelatin film, but decreased the moisture content and tensile strength. With nano-scale and uniform particles, the surface of films containing thymol nanoemulsions was smooth and continuous. Due to the hydrophobic property of lecithin and thymol, the water contact angle of gelatin film increased to above 90°. Moreover, sustained release of thymol from gelatin films was also observed, and these films exhibited effective inhibition activities against both Gram-positive and Gram-negative bacteria. Therefore, gelatin films containing thymol nanoemulsions co-emulsified by gelatin and lecithin may have great potentials to be applied as novel and GRAS biodegradable packaging materials to achieve the goal of extending the shelf life of food products.
•Gelatin films loaded with thymol nanoemulsions were prepared using the blend of gelatin and lecithin as emulsifiers.•Thymol nanoemulsion droplets were evenly distributed in the gelatin film matrix.•Addition of thymol nanoemulsions improved the mechanical properties and hydrophobicity of gelatin films.•Gelatin films loaded with thymol nanoemulsions exhibited efficient antimicrobial activities.
Thymol and eugenol derivatives as anti-leishmanial agents
In Northeastern Brazil visceral leishmaniasis is endemic with lethal cases among humans and dogs. Treatment is toxic and 5–10% of humans die ...despite treatment. The aim of this work was to survey natural active compounds to find new molecules with high activity and low toxicity against Leishmania infantum chagasi. The compounds thymol and eugenol were chosen to be starting compounds to synthesize acetyl and benzoyl derivatives and to test their antileishmanial activity in vitro and in vivo against L. i. chagasi. A screening assay using luciferase-expressing promastigotes was used to measure the growth inhibition of promastigotes, and an ELISA in situ was performed to evaluate the growth inhibition of amastigote. For the in vivo assay, thymol and eugenol derivatives were given IP to BALB/c mice at 100mg/kg/day for 30days. The thymol derivatives demonstrated the greater activity than the eugenol derivatives, and benzoyl-thymol was the best inhibitor (8.67±0.28μg/mL). All compounds demonstrated similar activity against amastigotes, and acetyl-thymol was more active than thymol and the positive control drug amphotericin B. Immunohistochemistry demonstrated the presence of Leishmania amastigote only in the spleen but not the liver of mice treated with acetyl-thymol. Thus, these synthesized derivatives demonstrated anti-leishmanial activity both in vitro and in vivo. These may constitute useful compounds to generate new agents for treatment of leishmaniasis.
Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow obstruction and inflammation. Natural products, such as monoterpenes, displayed anti-inflammatory and ...anti-oxidant activities and can be used as a source of new compounds to COPD treatment. Our aim was to evaluate, in an elastase-induced pulmonary emphysema in mice, the effects of and underlying mechanisms of three related natural monoterpenes (
-cymene, carvacrol and thymol) isolated from essential oil from leaves
Cham. (Verbenaceae).
Mices received porcine pancreatic elastase (PPE) and were treated with
-cymene, carvacrol, thymol or vehicle 30 min later and again on 7th, 14th and 28th days. Lung inflammatory profile and histological sections were evaluated.
In the elastase-instilled animals, the tested monoterpenes reduced alveolar enlargement, macrophages and the levels of IL-1β, IL-6, IL-8 and IL-17 in bronchoalveolar lavage fluid (BALF), and collagen fibers, MMP-9 and p-65-NF-κB-positive cells in lung parenchyma (
< 0.05). All treatments attenuated levels of 8-iso-PGF2α but only thymol was able to reduced exhaled nitric oxide (
< 0.05).
Monoterpenes
-cymene, carvacrol and thymol reduced lung emphysema and inflammation in mice. No significant differences among the three monoterpenes treatments were found, suggesting that the presence of hydroxyl group in the molecular structure of thymol and carvacrol do not play a central role in the anti-inflammatory effects.
•Thymol was successfully loaded into zein nanoparticles using a low energy method.•Sodium caseinate and chitosan hydrochloride were used as the stabilizer layers.•Stabilized zein nanoparticles had a ...desirable redispersibility in water.•Improved encapsulation efficiency was achieved with double stabilizer layers.•Encapsulated thymol showed stronger antimicrobial activity for a longer time period.
Thymol-loaded zein nanoparticles stabilized with sodium caseinate (SC) and chitosan hydrochloride (CHC) were prepared and characterized. The SC stabilized nanoparticles had well-defined size range and negatively charged surface. Due to the presence of SC, the stabilized zein nanoparticles showed a shift of isoelectric point from 6.18 to 5.05, and had a desirable redispersibility in water at neutral pH after lyophilization. Coating with CHC onto the SC stabilized zein nanoparticles resulted in increased particle size, reversal of zeta potential value from negative to positive, and improved encapsulation efficiency. Both thymol-loaded zein nanoparticles and SC stabilized zein nanoparticles had a spherical shape and smooth surface, while the surfaces of CHC-SC stabilized zein nanoparticles seemed rough and had some clumps. Encapsulated thymol was more effective in suppressing gram-positive bacterium than un-encapsulated thymol for a longer time period.
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