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1.
Molecules ; 26(14)2021 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-34299454

RESUMO

In this study, a new broth macrodilution volatilization method for the simple and rapid determination of the antibacterial effect of volatile agents simultaneously in the liquid and vapor phase was designed with the aim to assess their therapeutic potential for the development of new inhalation preparations. The antibacterial activity of plant volatiles (ß-thujaplicin, thymohydroquinone, thymoquinone) was evaluated against bacteria associated with respiratory infections (Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes) and their cytotoxicity was determined using a modified thiazolyl blue tetrazolium bromide assay against normal lung fibroblasts. Thymohydroquinone and thymoquinone possessed the highest antibacterial activity against H. influenzae, with minimum inhibitory concentrations of 4 and 8 µg/mL in the liquid and vapor phases, respectively. Although all compounds exhibited cytotoxic effects on lung cells, therapeutic indices (TIs) suggested their potential use in the treatment of respiratory infections, which was especially evident for thymohydroquinone (TI > 34.13). The results demonstrate the applicability of the broth macrodilution volatilization assay, which combines the principles of broth microdilution volatilization and standard broth macrodilution methods. This assay enables rapid, simple, cost- and labor-effective screening of volatile compounds and overcomes the limitations of assays currently used for screening of antimicrobial activity in the vapor phase.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Óleos Voláteis/farmacologia , Administração por Inalação , Antibacterianos/análise , Bactérias/efeitos dos fármacos , Benzoquinonas/administração & dosagem , Benzoquinonas/farmacologia , Haemophilus influenzae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Monoterpenos/administração & dosagem , Monoterpenos/farmacologia , Óleos Voláteis/química , Staphylococcus aureus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Streptococcus pyogenes/efeitos dos fármacos , Timol/administração & dosagem , Timol/análogos & derivados , Timol/farmacologia , Tropolona/administração & dosagem , Tropolona/análogos & derivados , Tropolona/farmacologia , Compostos Orgânicos Voláteis/química , Compostos Orgânicos Voláteis/farmacologia , Volatilização
2.
Phytochemistry ; 190: 112864, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34311279

RESUMO

Historically, essential oils and their lead molecules have been extensively recognised for their anti-infective properties. In this context, certain volatile phenolics (VPs) have emerged as important antimicrobial compounds with excellent inhibitory activity against pathogenic bacteria and fungi, which further extends to drug-resistant and biofilm-forming micro-organisms. In this review, we aim to collate and discuss a number of published papers on the anti-infective activities of naturally occurring VPs with special emphasis on eugenol, isoeugenol, thymol and carvacrol, using Scopus Web of Science and PubMed databases. The biosynthesis and extraction of these VPs are discussed, while particular attention is given to their broad-spectrum antimicrobial activity and the mechanisms of action. We highlight combinational studies of the VPs with other phytocompounds and with commercially available drugs, which may be a promising and a rewarding future approach to combat antimicrobial resistance. These VPs alone, or concomitantly with other compounds or drugs, have the potential to be incorporated into different formulations for biomedical applications. An in-depth assessment of 2310 articles retrieved from the Scopus database spanning a 35-year period indicated 23.1% increase in global publication growth in VPs anti-infective research, with authors from Italy, Portugal and Austria dominating the research landscape. The dominant areas of investigations are identified as antimicrobial activity, antibacterial mechanism of action, antifungal mechanism of action, extraction methods and phytochemistry, use in the food industry, and for oral and dental anti-infective activity. Specific research areas, which require future attention include; antituberculosis research, nanoparticle formulation of antimicrobial active VP molecules, preclinical and clinical trials. The antimicrobial testing of isoeugenol was found to be the least studied of the VPs and this requires further attention.


Assuntos
Anti-Infecciosos , Óleos Voláteis , Preparações Farmacêuticas , Anti-Infecciosos/farmacologia , Fungos , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia , Timol/farmacologia
3.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200464

RESUMO

Due to lifespan extension and changes in global climate, the increase in mycoses caused by primary and opportunistic fungal pathogens is now a global concern. Despite increasing attention, limited options are available for the treatment of systematic and invasive mycoses, owing to the evolutionary similarity between humans and fungi. Although plants produce a diversity of chemicals to protect themselves from pathogens, the molecular targets and modes of action of these plant-derived chemicals have not been well characterized. Using a reverse genetics approach, the present study revealed that thymol, a monoterpene alcohol from Thymus vulgaris L., (Lamiaceae), exhibits antifungal activity against Cryptococcus neoformans by regulating multiple signaling pathways including calcineurin, unfolded protein response, and HOG (high-osmolarity glycerol) MAPK (mitogen-activated protein kinase) pathways. Thymol treatment reduced the intracellular concentration of Ca2+ by controlling the expression levels of calcium transporter genes in a calcineurin-dependent manner. We demonstrated that thymol decreased N-glycosylation by regulating the expression levels of genes involved in glycan-mediated post-translational modifications. Furthermore, thymol treatment reduced endogenous ergosterol content by decreasing the expression of ergosterol biosynthesis genes in a HOG MAPK pathway-dependent manner. Collectively, this study sheds light on the antifungal mechanisms of thymol against C. neoformans.


Assuntos
Antifúngicos/farmacologia , Criptococose/tratamento farmacológico , Cryptococcus neoformans/efeitos dos fármacos , Timol/farmacologia , Calcineurina/metabolismo , Criptococose/metabolismo , Cryptococcus neoformans/metabolismo , Ergosterol/farmacologia , Proteínas Fúngicas/metabolismo , Humanos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Monoterpenos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Thymus (Planta)/química
4.
J Agric Food Chem ; 69(25): 6958-6967, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34152748

RESUMO

The semisynthesis of 15 new thymol derivatives was achieved through Williamson synthesis and copper-catalyzed azide-alkyne cycloaddition (CuAAC) approaches. The reaction of CuAAC using the "Click Chemistry" strategy, in the presence of an alkynyl thymol derivative and commercial or prepared azides, provided nine thymol derivatives under microwave irradiation. This procedure reduces reaction time and cost. All molecular entities were elucidated by 1H and 13C NMR, IR, and HRMS data. These derivatives were evaluated in vitro for their fungicidal activity against Fusarium solani sp. Among the nine triazolic thymol derivatives obtained, seven of them were found to have moderated antifungal activity. In contrast, naphthoquinone/thymol hybrid ether 2b displayed activity comparable with that of the commercial fungicide thiabendazole. The structure-activity relationship for the most active compound 2b was discussed, and the mode of action was predicted by a possible binding to the fungic ergosterol and interference of osmotic balance of K+ into the extracellular medium.


Assuntos
Fungicidas Industriais , Fusarium , Alcinos , Antifúngicos/farmacologia , Química Click , Fungicidas Industriais/farmacologia , Timol/farmacologia
5.
Molecules ; 26(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066411

RESUMO

Polyvinyl chloride (PVC), polypropylene (PP), polyethylene (PE), and stainless steel (SS) are commonly used in medicine and food production technologies. During contact with microorganisms on the surface of these materials, a microbial biofilm is formed. The biofilm structure is difficult to remove and promotes the development of pathogenic bacteria. For this reason, the inhibition of biofilm formation in medical and food production environments is very important. For this purpose, five naturally occurring compounds were used for antimicrobial screening tests. The two with the best antimicrobial properties were chosen to inhibit the biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa. After 3 days of exposure, thymol reduced the amount of biofilm of Pseudomonas aeruginosa within the range of 70-77% and 52-75% for Staphylococcus aureus. Carvacrol inhibited the formation of biofilms by up to 74-88% for Pseudomonas aeruginosa and up to 86-100% for Staphylococcus aureus. Those phenols decreased the enzyme activity of the biofilm by up to 40-100%. After 10 days of exposure to thymol, biofilm formation was reduced by 80-100% for Pseudomonas aeruginosa and by about 79-100% for Staphylococcus aureus. Carvacrol reduced the amount of biofilm by up to 91-100% for Pseudomonas aeruginosa and up to 95-100% for Staphylococcus aureus.


Assuntos
Biofilmes/efeitos dos fármacos , Cimenos/farmacologia , Testes de Sensibilidade Microbiana , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Timol/farmacologia , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Química Farmacêutica/tendências , Tecnologia de Alimentos/tendências , Hidrólise , Teste de Materiais , Aço Inoxidável , Propriedades de Superfície
6.
Ecotoxicol Environ Saf ; 221: 112435, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34171690

RESUMO

The present work was designed to assess the potential ameliorative effect of thymol on the testicular toxicity caused by imidacloprid (IMI) in adult male rats. Forty adult male rats were allocated into four groups; control group was given corn oil, thymol-treated group (30 mg/kg b.wt), IMI-treated group (22.5 mg/kg b.wt), and IMI + thymol-treated group. All administrations were done by gavage every day for duration of 56 days. As a result, the IMI exposure caused a significant decline in the body weight change, reproductive organ weights, sperm functional parameters, and serum level of testosterone, widespread histological alterations, and apoptosis in the testis. Additionally, the IMI-treated rats exhibited a remarkable increment in the serum levels of follicle stimulating hormone and luteinizing hormone. Also, IMI induced testicular oxidative stress, as indicated by elevated malondialdehyde (MDA) levels and a marked decline in the activity of antioxidant enzymes and reduced glutathione (GSH), and total antioxidant capacity (TAC) levels. Moreover, IMI treatment significantly downregulated the mRNA expression of steroidogenic genes and proliferating cell nuclear antigen (PCNA) immunoexpression in the testicular tissue. However, thymol co-administration significantly mitigated the IMI-induced toxic effects. Our findings suggested that IMI acts as a male reproductive toxicant in rats and thymol could be a potential therapeutic option for IMI reprotoxic impacts.


Assuntos
Apoptose/genética , Neonicotinoides/toxicidade , Nitrocompostos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Testículo/efeitos dos fármacos , Timol/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Masculino , Tamanho do Órgão/efeitos dos fármacos , Ratos , Espermatozoides/efeitos dos fármacos , Testosterona/sangue
7.
Vet Parasitol ; 296: 109501, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34147769

RESUMO

The present study aimed to develop a microemulsion formulation containing thymol and eugenol for field control of Rhipicephalus sanguineus sensu lato on dogs, as well to evaluate its safety and the physical characteristics of the formulation. The microemulsion using thymol and eugenol (5.0 + 5.0 mg/mL) had as vehicles water, propylene glycol, polysorbate 80 and canola oil. On the next day the preparation (formulation freshly prepared) and after 24 months, the size of the microemulsion droplets, polydispersion index (PdI), organoleptic properties (color, viscosity), and presence of precipitate in the microemulsion were evaluated. For the field assay, on day -1, 10 English Cocker Spaniel dogs were experimentally infested with 200 larvae, 100 nymphs and 30 adults of R. sanguineus s.l. On day 0, after tick counts, the animals were divided into two groups: treated with the freshly prepared microemulsion (10 mL/kg), and control, which received the vehicle (10 mL/kg). Tick counts on dogs were performed daily for three more days. Engorged females were recovered from the dogs and their biological and reproductive parameters were monitored. The dogs' clinical parameters (temperature, mucosa color, and general physical condition) were evaluated daily. In addition, blood samples were collected before infestation to verify hematological (packed cell volume) and biochemical parameters (total serum protein, albumin, globulins, creatinine, urea, alanine transaminase, aspartate aminotransferase, and alkaline phosphatase). Freshly prepared and 24-month aged microemulsions had droplets with mean sizes of 30.94 nm and 27.93 nm, and PdI values of 0.214 and 0.161, respectively. In addition, no difference in the organoleptic properties and no precipitation formation were observed, indicating physical stability. Treatment with the microemulsion resulted in reduction of larvae (p < 0.05) parasitizing the dogs on day 1 while the number of nymphs and adults was not reduced (P> 0.05). In the evaluation of the reproductive biology of engorged females, the larval hatchability (%) was compromised (p < 0.05), and the microemulsion had control rate of 85.5 %. The microemulsion and its vehicles did not change the clinical, hematological and biochemical parameters of the dogs. We concluded that the microemulsion was efficient against R. sanguineus s.l. by reducing the number of larvae and affecting the reproductive parameters of engorged females, safe for dogs, and stable (physical stability) during a two-year interval.


Assuntos
Doenças do Cão , Emulsões , Rhipicephalus sanguineus , Infestações por Carrapato , Animais , Doenças do Cão/tratamento farmacológico , Doenças do Cão/prevenção & controle , Cães , Emulsões/farmacologia , Emulsões/normas , Eugenol/farmacologia , Eugenol/uso terapêutico , Feminino , Larva , Ninfa , Rhipicephalus sanguineus/efeitos dos fármacos , Segurança , Timol/farmacologia , Timol/uso terapêutico , Infestações por Carrapato/tratamento farmacológico , Infestações por Carrapato/prevenção & controle , Infestações por Carrapato/veterinária
8.
Int J Biol Macromol ; 183: 753-759, 2021 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-33932425

RESUMO

Recently, the improvement of gelatin-based films for usage in food packaging has attracted more attention owing to their non-toxicity, biodegradability, availability, and renewability. In the current study, the improved gelatin-based films were produced using covalent interaction through dialdehyde kappa-carrageenan (DAK-car) and thymol-loaded zein nanoparticle content. The influences of DAK-car into the matrix of gelatin films (GEL) on the structural, total soluble matter (TSM), moisture content (MC), and water vapor permeability (WVP), and mechanical properties were investigated. After the formation of covalent crosslinking amongst the amino groups of GEL and the dialdehyde groups of DAK-car with the blending ratio of 1:2 (GEL 4% w/v): (DAK-car 1% w/v), a remarkably (p < 0.05) reduction was saw in TSM, MC, and WVP of film. The tensile strength of this film (72.26 ± 0.3 MPa) was ~20-fold higher compared with pure GEL film. It should also be noted that the presence of zein nanoparticles (ZNPs) did not have a notably effect on improving the attributes of gelatin-based film. However, the presence of thymol in concentrations of 0.25 and 0.5 mg/mL showed acceptable antioxidant and antimicrobial activities. As a result, GEL/DAK-car with blending ratio of 1:2 containing thymol-loaded ZNPs films demonstrated the valuable potential for application in active food packaging.


Assuntos
Anti-Infecciosos/farmacologia , Carragenina/química , Gelatina/química , Timol/farmacologia , Zeína/química , Anti-Infecciosos/química , Embalagem de Alimentos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletroquímica de Varredura , Nanopartículas , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Resistência à Tração , Termogravimetria , Timol/química
9.
Molecules ; 26(9)2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946153

RESUMO

Leaves of Lippia thymoides (Verbenaceae) were dried in an oven at 40, 50 and 60 °C and the kinetic of drying and the influence of the drying process on the chemical composition, yield, and DPPH radical scavenging activity of the obtained essential oils were evaluated. The composition of the essential oils was determined with gas chromatography-mass spectrometry and gas chromatography-flame ionization detection analyses. The influence of drying on the chemical composition of the essential oils of L. thymoides was evaluated by multivariate analysis, and their antioxidant activity was investigated via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The Midilli model was the most appropriate to describe the behavior of drying kinetic data of L. thymoides leaves. Thymol was the major compound for all analyzed conditions; the maximum content was obtained from fresh leaves (62.78 ± 0.63%). The essential oils showed DPPH radical scavenging activity with an average of 73.10 ± 12.08%, and the fresh leaves showed higher inhibition (89.97 ± 0.31%). This is the first study to evaluate the influence of drying on the chemical composition and antioxidant activity of L. thymoides essential oils rich in thymol.


Assuntos
Antioxidantes/química , Lippia/química , Óleos Voláteis/química , Óleos Vegetais/química , Timol/química , Antioxidantes/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Óleos Voláteis/farmacologia , Folhas de Planta/química , Óleos Vegetais/farmacologia , Temperatura , Timol/farmacologia
10.
Curr Microbiol ; 78(5): 1846-1855, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33861370

RESUMO

Bovine mastitis is an infectious disease that affects the mammary gland of dairy cattle with considerable economic losses. Staphylococcus aureus is the main microorganism involved in this highly contagious process, and the treatment is only using antibiotics. Currently, the search for new treatment and/or compounds is still in need due to microbial resistance. In this work, we evaluated the potential of eugenol and thymol derivatives against S. aureus strains from bovine mastitis. On that purpose, nine derivatives were synthesized from eugenol and thymol (1-9), and tested against 15 strains of S. aureus from subclinical bovine mastitis. Initially, the strains were evaluated for the biofilm production profile, and those with strong adherence were selected to the antimicrobial sensitivity determination in the Minimum Inhibitory Concentration (MIC) assays. Herein the compounds toxicity was also evaluated by in silico analysis using Osiris DataWarrior® software. The results showed that 60% of the strains were considered strongly adherent and three strains (S. aureus 4271, 4745 and 4746) were selected for the MIC tests. Among the nine eugenol and thymol derivatives tested, four were active against the evaluated strains (MIC = 32 µg mL-1) within CLSI standard values. In silico analysis showed that all derivatives had cLopP < 5, cLogS > - 4 and TPSA < 140 Å2, and similar theoretical toxicity parameters to some antibiotics currently on the market. These molecules also showed negative drug-likeness values, pointing to the originality of these structures and theoretical feasibility on escaping of resistance mechanism and act against resistant strains. Thus, these eugenol derivatives may be considered as promising for the development of new treatments against bovine mastitis and future exploring on this purpose.


Assuntos
Mastite Bovina , Infecções Estafilocócicas , Animais , Antibacterianos/farmacologia , Bovinos , Eugenol/farmacologia , Feminino , Mastite Bovina/tratamento farmacológico , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/veterinária , Staphylococcus aureus , Timol/farmacologia
11.
Molecules ; 26(9)2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922682

RESUMO

The European Union is promoting regulatory changes to ban fungicides because of the impact their use has on the ecosystem and the adverse effects they can pose for humans. An ecofriendly alternative to these chemicals to fight against fungal species with low toxicity is essential oils and their compounds extracted from aromatic plants. The purpose of this study was to evaluate the in vitro antifungal capacity of the botanical compounds eugenol, carvacrol, thymol, and cinnamaldehyde, and the synergy or antagonism of their mixtures, against Botryotinia fuckeliana and Rhizoctonia solani. Different bioassays were performed at doses of 300, 200, 150, and 100 µg/mL using pure commercial compounds and their combination in potato dextrose agar culture medium. Growth rate and the mycelium growth inhibition parameters were calculated. Phenolic compounds and their combination inhibited the development of species at the different concentrations, with fungicidal or fungistatic activity shown under almost all the tested conditions. When comparing the growth rates of the species in the control plates and treatments, the statistical analysis showed that there were statistically significant differences. The mixture of compounds improved fungicidal activity against the studied species and at a lower concentration of monoterpenes.


Assuntos
Antifúngicos/farmacologia , Botrytis/efeitos dos fármacos , Rhizoctonia/efeitos dos fármacos , Acroleína/análogos & derivados , Acroleína/farmacologia , Ascomicetos/efeitos dos fármacos , Timol/farmacologia
12.
Bioorg Med Chem ; 38: 116136, 2021 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-33894490

RESUMO

Natural product produced by plants has been the backbone for numerous anticancer agents. In the present work, natural bioactive thymol based 1,2,3-triazole hybrids have been synthesized and evaluated for anticancer activity in MCF-7 and MDA-MB-231 cancer cells. The synthesized molecules displayed desired pharmacokinetic predictions for an orally available drug. Among the synthesized hybrids, compound 4-((2-isopropyl-5-methylphenoxy)methyl)-1-o-tolyl-1H-1,2,3-triazole (10) was the most potent (IC50 6.17 µM) showing comparable cytotoxity to tamoxifen (IC50 5.62 µM) and 3.2 fold inhibition to 5-fluorouracil (IC50 20.09 µM) against MCF-7 cancer cells. Whereas against MDA-MB-231 cancer cells, compound 10 (IC50 10.52 µM) and 3-(4-((2-isopropyl-5-methylphenoxy)methyl)-1H-1,2,3-triazol-1-yl)benzoic acid (12) (IC50 11.41 µM) displayed 1.42 and 1.3 fold inhibition, respectively to tamoxifen (IC50 15.01 µM) whereas 2.4 fold and 2.2 activity to 5-Florouracil (IC50 25.31 µM). Furthermore, 10 and 12 significantly inhibited thymidylate synthase enzyme with 2.4 and 1.26 fold activity to standard drug, Pemetrexed (IC50 5.39 µM) suggesting their mode of action as thymidylate synthase inhibitors. Cell cycle arrest and annexin V induced apoptosis study of compound 10 showed cell cycle arrest at the G2/M phase and induction of apoptosis in MCF-7 cells. The molecular docking was accomplished onto thymidylate synthase (TS) protein. The active compounds exhibited promising binding interactions and binding affinities into active sites. Finally, density functional theory (DFT) calculations including chemical reactivity and molecular electrostatic potential (MEP) have been performed to confirm the data obtained from docking and biological experiments. The results from this study inferred that compound 10 could be served as a lead molecule for the treatment of breast cancer.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Simulação de Acoplamento Molecular , Timidilato Sintase/antagonistas & inibidores , Timol/farmacologia , Triazóis/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Feminino , Células HEK293 , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , Timidilato Sintase/metabolismo , Timol/química , Triazóis/síntese química , Triazóis/química
13.
Biomolecules ; 11(3)2021 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800308

RESUMO

Fresh vegetables and salads are increasingly implicated in outbreaks of foodborne infections, such as those caused by Listeria monocytogenes, a dangerous pathogen that can attach to the surfaces of the equipment creating robust biofilms withstanding the killing action of disinfectants. In this study, the antimicrobial efficiency of a natural plant terpenoid (thymol) was evaluated against a sessile population of a multi-strain L. monocytogenes cocktail developed on stainless steel surfaces incubated in lettuce broth, under optimized time and temperature conditions (54 h at 30.6 °C) as those were determined following response surface modeling, and in comparison, to that of an industrial disinfectant (benzalkonium chloride). Prior to disinfection, the minimum bactericidal concentrations (MBCs) of each compound were determined against the planktonic cells of each strain. The results revealed the advanced killing potential of thymol, with a concentration of 625 ppm (= 4 × MBC) leading to almost undetectable viable bacteria (more than 4 logs reduction following a 15-min exposure). For the same degree of killing, benzalkonium chloride needed to be used at a concentration of at least 20 times more than its MBC (70 ppm). Discriminative repetitive sequence-based polymerase chain reaction (rep-PCR) also highlighted the strain variability in both biofilm formation and resistance. In sum, thymol was found to present an effective anti-listeria action under environmental conditions mimicking those encountered in the salad industry and deserves to be further explored to improve the safety of fresh produce.


Assuntos
Alface/microbiologia , Listeria monocytogenes/efeitos dos fármacos , Timol/farmacologia , Compostos de Benzalcônio/farmacologia , Temperatura
14.
Front Immunol ; 12: 633621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777020

RESUMO

One of the main targets for the use of phytogenics in aquafeeds is the mucosal tissues as they constitute a physical and biochemical shield against environmental and pathogenic threats, comprising elements from both the innate and acquired immunity. In the present study, the modulation of the skin transcriptional immune response, the bacterial growth capacity in skin mucus, and the overall health condition of gilthead seabream (Sparus aurata) juveniles fed a dietary supplementation of garlic essential oil, carvacrol, and thymol were assessed. The enrichment analysis of the skin transcriptional profile of fish fed the phytogenic-supplemented diet revealed the regulation of genes associated to cellular components involved in the secretory pathway, suggesting the stimulation, and recruitment of phagocytic cells. Genes recognized by their involvement in non-specific immune response were also identified in the analysis. The promotion of the secretion of non-specific immune molecules into the skin mucus was proposed to be involved in the in vitro decreased growth capacity of pathogenic bacteria in the mucus of fish fed the phytogenic-supplemented diet. Although the mucus antioxidant capacity was not affected by the phytogenics supplementation, the regulation of genes coding for oxidative stress enzymes suggested the reduction of the skin oxidative stress. Additionally, the decreased levels of cortisol in mucus indicated a reduction in the fish allostatic load due to the properties of the tested additive. Altogether, the dietary garlic, carvacrol, and thymol appear to promote the gilthead seabream skin innate immunity and the mucus protective capacity, decreasing its susceptibility to be colonized by pathogenic bacteria.


Assuntos
Imunidade Inata/efeitos dos fármacos , Muco/metabolismo , Óleos Voláteis/farmacologia , Dourada/imunologia , Via Secretória/efeitos dos fármacos , Pele/efeitos dos fármacos , Ração Animal/análise , Animais , Aquicultura , Cimenos/química , Cimenos/farmacologia , Suplementos Nutricionais/análise , Alho/química , Imunidade Inata/genética , Imunidade nas Mucosas/efeitos dos fármacos , Muco/efeitos dos fármacos , Muco/microbiologia , Óleos Voláteis/classificação , Dourada/genética , Via Secretória/imunologia , Timol/química , Timol/farmacologia
15.
Commun Biol ; 4(1): 408, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767385

RESUMO

The emergence of multidrug-resistant bacteria has become a real threat and we are fast running out of treatment options. A combinatory strategy is explored here to eradicate multidrug-resistant Staphlococcus aureus and Pseudomonas aeruginosa including planktonic cells, established biofilms, and persisters as high as 7.5 log bacteria in less than 30 min. Blue-laser and thymol together rapidly sterilized acute infected or biofilm-associated wounds and successfully prevented systematic dissemination in mice. Mechanistically, blue-laser and thymol instigated oxidative bursts exclusively in bacteria owing to abundant proporphyrin-like compounds produced in bacteria over mammalian cells, which transformed harmless thymol into blue-laser sensitizers, thymoquinone and thymohydroquinone. Photo-excitations of thymoquinone and thymohydroquinone augmented reactive oxygen species production and initiated a torrent of cytotoxic events in bacteria while completely sparing the host tissue. The investigation unravels a previously unappreciated property of thymol as a pro-photosensitizer analogous to a prodrug that is activated only in bacteria.


Assuntos
Lasers , Fármacos Fotossensibilizantes/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos da radiação , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/efeitos da radiação , Timol/farmacologia , Benzoquinonas/metabolismo , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/fisiologia , Staphylococcus aureus Resistente à Meticilina/efeitos da radiação , Plâncton/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia , Staphylococcus aureus/fisiologia , Timol/análogos & derivados , Timol/metabolismo
16.
Life Sci ; 274: 119335, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33713663

RESUMO

AIM: Evaluating the possible protective effect of thymol as an approach against 1,2 N,N-dimethylhydrazine and/or high-fat diet (HFD)-induced colon cancer. MAIN METHODS: Adult male Wistar rats were divided into 7 groups, namely a normal control group, colon cancer groups received DMH (40 mg/kg i.p., twice weekly), 20% HFD and DMH/HFD, thymol (20 mg/kg/day, p.o.), thymol/DMH and thymol/DMH/HFD (treatment of all groups continued for 16 weeks). KEY FINDINGS: Thymol significantly reduced the elevated serum levels of colon related tumor markers carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) as well as the apoptotic marker, caspase-3 compared with the colon cancer group. In addition, it mitigated colonic tissue oxidative stress markers and inflammatory mediators. Moreover, the histopathological study revealed reduction of mucous secretion with elongated nuclei, frequent mitotic figures, focal nuclear stratification, mild interstitial edema, and markedly dilated congested blood vessels, aberrant crypt foci (ACF); adenoma with moderate to severe dysplasia of colon corrected by thymol treatment. SIGNIFICANCE: The administration of thymol had a promising preclinical protective efficacy and could be considered as a new strategy for the prophylaxis from colon cancer in clinical practices.


Assuntos
1,2-Dimetilidrazina/toxicidade , Anticarcinógenos/farmacologia , Carcinógenos/toxicidade , Neoplasias do Colo/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , NF-kappa B/metabolismo , Timol/farmacologia , Animais , Neoplasias do Colo/etiologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Masculino , NF-kappa B/genética , Ratos , Ratos Wistar
17.
Int J Parasitol Drugs Drug Resist ; 15: 126-133, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33647675

RESUMO

Cryptosporidium parvum is a protozoan parasite that infects intestinal epithelial cells causing malabsorption and severe diarrhea. The monoterpene thymol has been reported to have antifungal and antibacterial properties but less is known about the antiparasitic effect of this compound. Terpenes are sometimes unsuitable for therapeutic and food applications because of their instability. Esterification of terpenes eliminates this disadvantage. The present study evaluates the effects of thymol (Th) and a thymol ester, thymol octanoate (TO), against C. parvum infectivity in vitro. The cytotoxicity IC50 value for TO after 24 h of treatment was 309.6 µg/mL, significantly higher than that of Th (122.5 µg/mL) in a human adenocarcinoma cell line (HCT-8). In the same way, following 48 h of treatment, the cytotoxicity IC50 value for TO was significantly higher (139 µg/mL) than that of Th (75.5 µg/mL). These results indicate that esterification significantly reduces Th cytotoxicity. Dose-dependent effects were observed for TO and Th when both parasite invasion and parasite growth assays were evaluated. When evaluated for their activity against C. parvum growth cultured in vitro in HCT-8 cells, the anti-cryptosporidial IC50 values were 35.5 and 7.5 µg/mL, for TO and Th, respectively. Together, these findings indicate that esterified thymol has anti-cryptosporidial effect comparable with its parental compound thymol, but with improved safety margins in mammalian cells and better physicochemical properties that could make it more suitable for diverse applications as an antiparasitic agent.


Assuntos
Criptosporidiose , Cryptosporidium parvum , Cryptosporidium , Animais , Técnicas de Cultura de Células , Ésteres/farmacologia , Humanos , Timol/farmacologia
18.
J Econ Entomol ; 114(1): 397-402, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33558901

RESUMO

Some plant essential oil constituents, such as monoterpenoids and phenylpropanoids, are promising insecticides in some situations and for certain insect pests. They vary in their toxicity, depending on the target insect. Moths (Lepidoptera) appear susceptible to these compounds, making them of promise for use against greater wax moths (Galleria mellonella Fabricius, (Lepidoptera: Pyrallidae), GWM), an important pest of western honey bee (Apis mellifera Linnaeus. (Hymenoptera: Apidae)) colonies. We determined the LC50 for GWM larvae or LD50 for GWM adults of select compounds (thymol, carvacrol, (S)-(+)-carvone, estragole, citral, linalool, (S)-(-)-limonene, and γ-terpinene). Concentrations between 8 and 2,266 µg/cm3 were mixed into the diets of GWM larvae and doses ranging between 0.08 and 70.3 mg per adult were applied topically to the abdomens of GWM adults. Lethal concentrations and doses were calculated after of 72 h of exposure. All eight compounds showed insecticidal activity against all tested stages of GWMs. Thymol (LC50 µg/cm3 (95% CI) = 21 [9-56], carvacrol = 46 [26-79], citral = 63 [30-134], and carvone = 76 [33-201]) had the highest toxicity toward GWM larvae. The hydrocarbons limonene (296 [231-377]), estragole (466 [354-611]), and γ-terpinene (729 [630-857]) had the lowest toxicity toward GWM larvae. Thymol had the highest toxicity towards GWM adults (LD50 (CI) = 0.5 [0.4-0.8] mg/adult). However, carvacrol (11.6 [10.1-13.6]), linalool (12.9 [9.3-17.8]), and limonene (15.8 [13.1-19.2]) were less toxic to GWM larvae. Our data show that select plant essential oil constituents are promising controls of GWM.


Assuntos
Inseticidas , Mariposas , Óleos Voláteis , Animais , Abelhas , Larva , Óleos Vegetais , Timol/farmacologia
19.
Food Chem ; 347: 129051, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33476921

RESUMO

A way to reduce food waste is related to the increase of the shelf-life of food as a result of improving the package type. An innovative active food packaging material based on cocrystallization of microbiologically active compounds present in essential oils i.e. carvacrol, thymol and cinnamaldehyde was developed following the Quality by Design principles. The selected active components were used to produce antimicrobial plastic films with solidified active ingredients on their surface characterized by antimicrobial properties against four bacterial strains involved in fruit and vegetable spoilage. The developed packaging prototypes exhibited good antimicrobial activity in vitro providing inhibition percentage of 69 (±15)% by contact and inhibition diameters of 32 (±6) mm in the gas phase, along with a prolonged release of the active components. Finally, the prolonged shelf-life of grape samples up to 7 days at room temperature was demonstrated.


Assuntos
Anti-Infecciosos/química , Embalagem de Alimentos/métodos , Óleos Voláteis/química , Acroleína/análogos & derivados , Acroleína/química , Acroleína/farmacologia , Anti-Infecciosos/farmacologia , Cristalização , Cimenos/química , Cimenos/farmacologia , Escherichia coli/efeitos dos fármacos , Microbiologia de Alimentos , Qualidade dos Alimentos , Testes de Sensibilidade Microbiana , Salmonella typhimurium/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Timol/química , Timol/farmacologia
20.
Sci Rep ; 11(1): 1223, 2021 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441680

RESUMO

Plant essential oils are considered as important bio-sources for the development of natural and environmentally safe pest control tools due to their multiple modes of action on insects. In this paper we have evaluated the activity of commercially available thyme oil and its constituents thymol, carvacrol, and p-cymene, as potential disruptants of the pheromone-mediated communication in the major pest moths Spodoptera littoralis Boisduval (Lepidoptera: Noctuidae), and Grapholita molesta (Busck) (Lepidoptera: Tortricidae). In electroantennographic assays, the antennal response of males to thyme oil, thymol, and carvacrol was altered at high doses (103-104 µg), shifting the signal waveform into a biphasic negative-positive potential that caused a decay in the response. In wind tunnel assays, pheromone-mediated attraction of males of both species was interrupted in presence of thyme oil. Further trials demonstrated that thymol alone reduced the number of G. molesta and S. littoralis males landing on the pheromone source. This effect did not differ from that of thyme oil, although the latter provoked a significant reduction on downwind behavior steps in S. littoralis. Overall, our findings provide a preliminary basis for delving into the effect of thyme oil, and especially of its major constituent thymol, as potential mating disruptants of both species.


Assuntos
Mariposas/efeitos dos fármacos , Mariposas/fisiologia , Feromônios/farmacologia , Atrativos Sexuais/farmacologia , Comportamento Sexual Animal/efeitos dos fármacos , Timol/farmacologia , Animais , Cimenos/farmacologia , Masculino , Óleos Voláteis/farmacologia , Reprodução/efeitos dos fármacos , Thymus (Planta)/química
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