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1.
J Anim Sci ; 98(5)2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32280983

RESUMO

This research evaluated a feed additive (benzoic acid, eugenol, thymol, and piperine), associated or not with colistin, in weaned piglets feeding. The parameters evaluated were growth performance, apparent total tract digestibility (ATTD) of nutrients, diarrhea incidence, intestinal morphology, relative weights of digestive organs, microbial diversity, and the percentages of operational taxonomic units of microorganisms in the cecum content of pigs. One-hundred and eight crossbred piglets (5.3 ± 0.5 kg) were used in a three-phase feeding program (21 to 35, 36 to 50, 51 to 65 d of age) and fed a control diet with no inclusion of growth promoter feed additive, a diet with 40 ppm of colistin, a diet with 0.3% of alternative additive, and a diet with 0.3% of alternative additive and 40 ppm of colistin. The diets were based on corn, soybean meal, dairy products, and spray-dried blood plasma and formulated to provide 3.40, 3.38, and 3.20 Mcal of ME/kg and 14.5, 13.3, and 10.9 g/kg of digestible lysine, in phases 1, 2, and 3, respectively. The piglets were housed three per pen, with nine replicates per diet, in a complete randomized block design based on initial BW. The data were submitted to ANOVA and means were separated by Tukey test (5%), using SAS. Pigs fed diets with the alternative feed additive had greater (P < 0.05) ADG (114.3 vs. 91.8 g) and ADFI (190.1 vs. 163.3 g) in phase 1 than pigs fed diets without the product. The alternative additive improved (P < 0.05) ATTD of crude protein (CP) in phase 1 (71.0% vs. 68.6%), gross energy in phases 1 (77.4% vs. 75.2%) and 3 (79.0% vs. 77.1%), and dry matter in phase 3 (79.1% vs. 77.1%). The antibiotic inclusion in the diets increased (P < 0.05) ATTD of CP in phase 1 (71.5% vs. 68.2%). The alternative feed additive tended (P = 0.06) to increase (46%) normal feces frequency, decreased (P < 0.05) goblet cells count (104.3 vs. 118.1) in the jejunum, and decreased (P < 0.05) small intestine (4.60% vs. 4.93%) and colon (1.41% vs. 1.65%) relative weights, compared with pigs not fed with the alternative additive. There was a tendency (P = 0.09) for a lower concentration of Escherichia-Shigella (1.46% vs. 3.5%) and lower (P < 0.05) percentage of Campylobacter (0.52% vs. 10.21%) in the cecum content of piglets fed diets containing essential oils and benzoic acid compared with pigs fed diets without the alternative feed additive. The alternative feed additive was effective in improving growth performance, diets digestibility, and gut health in piglets soon after weaning.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Aditivos Alimentares/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Óleos Voláteis/farmacologia , Suínos/fisiologia , Alcaloides/farmacologia , Ração Animal/análise , Animais , Benzodioxóis/farmacologia , Ácido Benzoico/farmacologia , Dieta/veterinária , Digestão/efeitos dos fármacos , Eugenol/farmacologia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/fisiologia , Masculino , Nutrientes , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia , Soja , Suínos/crescimento & desenvolvimento , Suínos/microbiologia , Timol/farmacologia , Desmame , Zea mays
2.
Bratisl Lek Listy ; 121(2): 122-128, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32115964

RESUMO

BACKGROUND: Cancer is a major public health problem in many areas of the world. Many anticancer drugs in current clinical use have been isolated from plant species or are based on such substances. Thymol (5-methyl-2-isopropylphenol) is an oxygenated aromatic compound from monoterpene group. It is the main constituent of thyme essential oil and shows antioxidant, antiseptic and antiproliferative properties. The aim of this study is to determine the antiproliferative activity and apoptotic effect of thymol on prostate cancer (PC-3, DU145), breast cancer (MDA-MB-231), and lung cancer (KLN205) cell lines. METHODS: The cancer cells were treated with different concentrations of thymol (100, 200, 400, 600, 800 µM) at 24 h, 48 h and 72 h. The cell viability was investigated by MTT assay and analysis of apoptosis was determined with annexin V assay. RESULTS: The study showed the dose and time-dependent cytotoxic effect of thymol in PC-3, DU145, MDA-MB-231, and KLN205 cancer cell lines. Thymol significantly induced apoptosis in all groups in a dose-dependent manner. Statistical analysis showed a significant difference between thymol­treated cell lines compared to the control (p < 0.001). CONCLUSION: The data in the present study demonstrated that thymol has apoptotic and antiproliferative properties in lung, breast and prostate cancer cell lines. Thymol could serve as a potential therapeutic agent in the future (Fig. 5, Ref. 26).


Assuntos
Apoptose , Fenol , Timol , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Humanos , Masculino , Monoterpenos , Timol/farmacologia
3.
J Mycol Med ; 30(1): 100911, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32008964

RESUMO

Role of biofilm in disease development and enhance tolerance to antifungal drugs among Candida species has necessitated search for new anti-fungal treatment strategy. Interference in pathogenic biofilm development by new antifungal compounds is considered as an attractive anti-infective strategy. Therefore, the objective of this study was to evaluate Thymus vulgaris essential oil and its major active compound, thymol for their potential to inhibit and eradicate biofilms alone and in combination with antifungal drugs against Candida spp. with especial reference to Candida tropicalis. Anti-candidal efficacy of T. vulgaris and thymol in terms of minimum inhibitory concentration (MIC) was first determined to select the sub-MICs against C. albicans and C. tropicalis. Biofilm formation in the presence and absence of test agents was determined in 96-well microtiter plate by XTT reduction assay and effect of essential oils at sub-MICs of the test agents on biofilm development on glass surface was analysed by light and scanning electron microscopy. Synergistic interaction between essential oils and antifungal drugs were studied by checkerboard method. Effect of sub-MIC of T. vulgaris (0.5×MIC) and thymol (0.5×MIC) on biofilm formation showed a significant reduction (P<0.05) in biofilms. Light microscopy and SEM studies revealed disaggregation and deformed shape of C. albicans biofilm cells and reduced hyphae formation in C. tropicalis biofilm cells at sub-MICs of thymol. Significant effect of T. vulgaris and thymol was also recorded on pre-formed biofilms of both C. albicans and C. tropicalis. T. vulgaris and thymol also showed synergy with fluconazole against both in planktonic and biofilm mode of growth of C. albicans and C. tropicalis. However, synergy with amphotericin B is clearly evident only in planktonic Candida cells. Thyme oil and thymol alone or in combination with antifungal drugs can act as promising antibiofilm agent against drug resistant strains of Candida species and needs further in vivo study to synergise its therapeutic efficacy.


Assuntos
Antifúngicos/farmacologia , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida tropicalis/efeitos dos fármacos , Óleos Vegetais/farmacologia , Timol/farmacologia , Thymus (Planta)/química , Biofilmes/crescimento & desenvolvimento , Candida albicans/fisiologia , Candida tropicalis/fisiologia , Candidíase/microbiologia , Farmacorresistência Fúngica/efeitos dos fármacos , Sinergismo Farmacológico , Humanos , Testes de Sensibilidade Microbiana , Óleos Voláteis/farmacologia
4.
Int J Food Microbiol ; 320: 108519, 2020 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-31962221

RESUMO

A novel composite antimicrobial film (CAF), made from a pullulan-based biopolymer and polyethylene (PE) was developed and evaluated for controlling pathogens associated with muscle foods. Initially, CAFs were developed by incorporating thymol (T), nisin (N) and/or lauric arginate (LAE) into the pullulan layer and layering it on top of PE. The antimicrobial activity of the resulting CAFs was evaluated against cocktails of Shiga toxin-producing E. coli (STEC), Salmonella spp., Listeria monocytogenes (L. monocytogenes) and Staphylococcus aureus (S. aureus) in disk diffusion assays (DDAs). CAFs containing N were ineffective, while those containing T were effective for inhibiting the pathogens in DDAs. However, CAFs made with them did not exhibit desirable physical and mechanical properties since solvents (HCl and ethanol, respectively) interfered with the binding of pullulan to PE. Conversely, CAFs made with 0.5, 1 and 2.5% LAE maintained proper physical and mechanical characteristics and inhibited the four bacterial pathogens in DDAs. Based on these preliminary results, cocktails consisting of approximately 8 log10 CFU/ml of STEC, Salmonella, L. monocytogenes, or S. aureus were experimentally-inoculated onto raw beef, raw chicken breast, or ready-to-eat (RTE) turkey breast to obtain approximately 6.6 log10 CFU/cm2, aseptically transferred to CAFs containing 0.5, 1, or 2.5% LAE that were made into sachets/bags, vacuum packaged, sealed, and remaining microbial populations determined up to 28 days of refrigerated storage (4 °C). By day 28, CAFs containing 0.5, 1, and 2.5% LAE reduced: STEC by 1.13, 1.33 and 2.88 log10 CFU/cm2 respectively, on raw beef; Salmonella by 2.03, 2.12 and 3.01 log10 CFU/cm2 respectively, on raw chicken breast; L. monocytogenes by 1.12, 1.81 and 3.56 log10 CFU/cm2 respectively, on RTE turkey breast; and S. aureus by 0.68, 2.02 and 3.43 log10 CFU/cm2, respectively, on RTE turkey breast. CAFs may be of interest to the meat and poultry industry to control foodborne pathogens associated with these food products.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Embalagem de Alimentos/instrumentação , Carne/microbiologia , Animais , Arginina/análogos & derivados , Arginina/química , Arginina/farmacologia , Bactérias/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Embalagem de Alimentos/métodos , Glucanos/química , Glucanos/farmacologia , Nisina/química , Nisina/farmacologia , Timol/química , Timol/farmacologia
5.
Vet Parasitol ; 277: 108989, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31794909

RESUMO

The aim of this study was to investigate whether the combination of thymol with eugenol has a synergistic effect on the immature life stages of Rhipicephalus sanguineus sensu lato (s.l.), to evaluate the cost-benefit ratio of using these compounds in combination, and to develop a formulation combining thymol with eugenol with activity on immature stages of R. sanguineus s.l. To evaluate synergism, thymol and eugenol, combined (ratio 1:1) or not, were tested at concentrations of 2.5, 5.0, 10.0, 15.0 and 20.0 mg/mL on unfed larvae and nymphs using a larval packet test, and 0.625, 1.25, 2.5, 5.0 and 10 mg/mL on engorged larvae and nymphs using an immersion test. A cost estimate was calculated to produce 1 L of a solution containing a concentration of thymol and eugenol, combined or not, that could cause a tick mortality rate greater than 95 %. Finally, a formulation was developed, consisting of a micellar dispersion containing polymers (MDP), with thymol + eugenol (1:1), at concentrations of 2.5, 5.0, 10.0, 15.0 and 20.0 mg/mL, and the activity was evaluated on unfed and engorged larvae and nymphs. For unfed larvae and nymphs, concentrations of 2.5 and 5.0 mg/mL and 2.5, 5.0 and 10.0 mg/mL, respectively, presented synergistic effects. In tests with engorged larvae and nymphs, respective concentrations of 0.625, 1.25 and 2.5 mg/mL and 2.5 and 5.0 mg/mL had synergistic effects. The estimated costs for producing a solution of 1 L with efficacy greater than 95 % was $5.97 using only thymol (15 mg/mL), $ 5.93 using only eugenol (15 mg/mL), and $ 3.97 using thymol + eugenol (1:1 - 5,0 mg/mL). In tests with MDP, the combination of thymol + eugenol resulted in a mortality rate higher than 95 % at concentration of 10 mg/mL for unfed and engorged larvae and nymphs. Thus, the combination of thymol + eugenol, depending on the concentration, has synergistic effects and this combination lowers the cost for the active ingredients thymol and eugenol. The combination of thymol + eugenol in MDP had acaricidal activity against immature life stages of R. sanguineus s.l.


Assuntos
Eugenol/farmacologia , Rhipicephalus sanguineus/efeitos dos fármacos , Timol/farmacologia , Acaricidas/economia , Acaricidas/farmacologia , Animais , Sinergismo Farmacológico , Eugenol/economia , Estágios do Ciclo de Vida/efeitos dos fármacos , Timol/economia
6.
Artigo em Inglês | MEDLINE | ID: mdl-31683013

RESUMO

Thymol, a phenolic monoterpene, is well known for its antimicrobial, antifungal and antioxidant properties. In spite of wide use in oral care products, pharmaceutical and cosmetic preparation and in food industry, the effects of thymol on the neuronal activity and intrinsic properties have not been well studied. We studied the effects of thymol on the spontaneous activity and action potential properties of central neurons of snail Caucasotachea atrolabiata. Thymol (1 mM) altered action potentials characteristics and provoked epileptiform burst firing in snail neurons, which were partially reversible after washout. Before burst firing, action potentials had lower amplitude and maximum rising slope, while the threshold voltage was raised. These results suggest the inhibition of ion channels underlying action potential initiation and upstroke. The maximum falling slope and afterhyperpolarization were also considerably reduced, suggesting the inhibition of potassium channels. Thymol (0.5 mM) that was not able to induce burst firing in snail neurons, synergistically acted with potassium channel blocker, tetraethyl ammonium, to induce burst firing, which also supports the importance of potassium channel inhibition, especially delayed rectifier potassium channels, to the thymol-induced alteration of firing pattern. The thymol-induced burst firing seems to be dependent on both sodium and calcium currents. Our findings provide evidences for the ability of thymol in altering the firing mode of central neurons of snail, which apparently involves the inhibition of calcium and potassium currents. These results further support the interaction of thymol with ion channels and emphasize on the vulnerability of nervous system to this compound.


Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Sistema Nervoso Central/efeitos dos fármacos , Gastrópodes/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Bloqueadores dos Canais de Potássio/farmacologia , Timol/farmacologia , Potenciais de Ação/efeitos dos fármacos , Animais , Gastrópodes/fisiologia
7.
Food Microbiol ; 86: 103357, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31703857

RESUMO

We investigated combinations of gaseous essential oils (EO gases) for their synergistic inhibitory activities against Listeria monocytogenes on a laboratory medium and radish sprouts. The minimum inhibitory concentrations and minimum lethal concentrations of oregano, thyme thymol, and cinnamon bark EO gases against L. monocytogenes were 0.0781 µL/mL on nutrient agar supplemented with glucose and bromocresol purple (NGBA). A checkerboard assay showed that combinations of oregano and thyme thymol EO gases and of oregano and cinnamon bark EO gases exert the strongest synergistic antilisterial activity (fractional inhibitory concentration index [FICI] = 0.3750). A combination of thyme thymol and cinnamon bark EO gases also had a synergistic effect (FICI = 0.5000) on L. monocytogenes on NGBA. Combinations of oregano and thyme thymol EO gases were tested for synergistic antimicrobial activity against L. monocytogenes on radish sprouts. A combination of these gases, each at 0.313 µL/mL, caused a significant (P ≤ 0.05) reduction in the number of L. monocytogenes on radish sprouts compared with reductions caused by treatment with oregano or thyme thymol EO gas alone at the same concentration. Our findings provide information that will be useful when developing antimicrobial applications using EO gases to control L. monocytogenes in the food industry.


Assuntos
Antibacterianos/farmacologia , Listeria monocytogenes/efeitos dos fármacos , Óleos Voláteis/farmacologia , Origanum/química , Raphanus/microbiologia , Timol/farmacologia , Thymus (Planta)/química , Antibacterianos/química , Cinnamomum zeylanicum/química , Meios de Cultura/química , Meios de Cultura/metabolismo , Sinergismo Farmacológico , Gases/farmacologia , Listeria monocytogenes/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Óleos Voláteis/química , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Raphanus/crescimento & desenvolvimento , Timol/química
8.
Ecotoxicol Environ Saf ; 188: 109894, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31706239

RESUMO

Modulation of plant salt tolerance has been drawing great attention. Thymol is a kind of natural chemical that has been developed as anti-microbial reagent and medicine. To date, we still have limited knowledge about thymol-modulated plant physiology. In this work, physiological, histochemical, and biochemical methods were adopted to study thymol-conferred salt resistance in the root of rice (Oryza sativa). Thymol significantly rescued root growth under salt stress. Thymol ameliorated cell membrane damage, oxidative stress, ROS accumulation, and cell death in roots under salt stress. Thymol-attenuated oxidative stress may be resulted from the activation of anti-oxidative capacity, including both enzymatic and non-enzymatic system. Thymol treatment significantly decreased Na+ content in root cells upon salt stress, which might be ascribed to the upregulation of OsSOS1 (salt overly sensitive 1) facilitating Na+ exclusion. In addition, thymol stimulated the expression of genes encoding tonoplast OsNHX (Na+/H+antiporter), which may help root cells to compartmentalize Na+ in vacuole. The results of these works evidenced that thymol was capable of inducing salt tolerance by reestablishing ROS homeostasis and modulating cellular Na+ flux in rice roots. These findings may be applicable to improve crop growth in salinity area.


Assuntos
Antioxidantes/metabolismo , Homeostase/efeitos dos fármacos , Oryza/efeitos dos fármacos , Tolerância ao Sal/efeitos dos fármacos , Sódio/metabolismo , Timol/farmacologia , Íons/metabolismo , Oryza/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Plantas Tolerantes a Sal , Trocadores de Sódio-Hidrogênio/metabolismo
9.
Molecules ; 24(23)2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31817023

RESUMO

Essential oil of Origanum species is well known for antimicrobial activity, but only a few have been evaluated in narrow spectrum antiprotozoal assays. Herein, we assessed the antiprotozoal potential of Turkish Origanum onites L. oil and its major constituents against a panel of parasitic protozoa. The essential oil was obtained by hydrodistillation from the dried herbal parts of O. onites and analyzed by Gas Chromatography-Flame Ionization Detector (GC-FID) and Gas Chromatography coupled with Mass Spectrometry (GC-MS). The in vitro activity of the oil and its major components were evaluated against Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum. The main component of the oil was identified as carvacrol (70.6%), followed by linalool (9.7%), p-cymene (7%), γ-terpinene (2.1%), and thymol (1.8%). The oil showed significant in vitro activity against T. b. rhodesiense (IC50 180 ng/mL), and moderate antileishmanial and antiplasmodial effects, without toxicity to mammalian cells. Carvacrol, thymol, and 10 additional abundant oil constituents were tested against the same panel; carvacrol and thymol retained the oil's in vitro antiparasitic potency. In the T. b. brucei mouse model, thymol, but not carvacrol, extended the mean survival of animals. This study indicates the potential of the essential oil of O. onites and its constituents in the treatment of protozoal infections.


Assuntos
Antiprotozoários/administração & dosagem , Antiprotozoários/química , Óleos Voláteis/administração & dosagem , Óleos Voláteis/química , Origanum/química , Tripanossomíase Africana/tratamento farmacológico , Animais , Antiprotozoários/farmacologia , Cimenos/administração & dosagem , Cimenos/farmacologia , Modelos Animais de Doenças , Cromatografia Gasosa-Espectrometria de Massas , Concentração Inibidora 50 , Camundongos , Estrutura Molecular , Óleos Voláteis/farmacologia , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Timol/administração & dosagem , Timol/farmacologia , Trypanosoma brucei rhodesiense/efeitos dos fármacos
10.
BMC Microbiol ; 19(1): 294, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842755

RESUMO

BACKGROUND: Thymol is a phenolic compound used for its wide spectrum antimicrobial activity. There is a limited understanding of the antimicrobial mechanisms underlying thymol activity. To investigate this, E. coli strain JM109 was exposed to thymol at sub-lethal concentrations and after 16 rounds of exposure, isolates with a 2-fold increased minimal inhibitory concentration (MIC) were recovered (JM109-Thyr). The phenotype was stable after multiple sub-cultures without thymol. RESULTS: Cell morphology studies by scanning electron microscopy (SEM) suggest that thymol renders bacterial cell membranes permeable and disrupts cellular integrity. 1H Nuclear magnetic resonance (NMR) data showed an increase in lactate and the lactic acid family amino acids in the wild type and JM109-Thyr in the presence of thymol, indicating a shift from aerobic respiration to fermentation. Sequencing of JM109-Thyr defined multiple mutations including a stop mutation in the acrR gene resulting in a truncation of the repressor of the AcrAB efflux pump. AcrAB is a multiprotein complex traversing the cytoplasmic and outer membrane, and is involved in antibiotic clearance. CONCLUSIONS: Our data suggests that thymol tolerance in E. coli induces morphological, metabolic and genetic changes to adapt to thymol antimicrobial activity.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Timol/farmacologia , Permeabilidade da Membrana Celular , Farmacorresistência Bacteriana Múltipla , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Fermentação , Regulação Bacteriana da Expressão Gênica , Lactatos/metabolismo , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana , Mutação , Fenótipo , Proteínas Repressoras/genética
11.
Biofouling ; 35(9): 1026-1039, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31778072

RESUMO

The emergence and spread of multidrug-resistant (MDR) pathogenic bacteria is a clinical problem that requires novel anti-infective agents. Targeting pathogenic biofilms is considered a promising strategy to control bacterial infections. In this study, bioactive extracts of Carum copticum were investigated for their anti-biofilm efficacy against extended spectrum ß-lactamase (ESßL) producing MDR enteric bacteria. Thymol was also tested for its anti-biofilm properties, as gas chromatography-mass spectrometry revealed a high content (65.8%) of this phytochemical in the C. copticum methanolic extract. Biofilm inhibition was assessed in microtitre plates and further validated by light, electron and confocal laser microscopy. Sub-inhibitory concentrations of bioactive extracts of C. copticum and thymol significantly prevented biofilm development, ranging from 78.6 to 83.9% reductions. Microscopic analysis revealed that biofilms made by ESßL producing MDR enteric bacteria had a weakened structure, scattered microcolonies, and reduced cell density and thickness after exposure to the bioactive extracts and thymol.


Assuntos
Biofilmes/efeitos dos fármacos , Carum/química , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Extratos Vegetais/farmacologia , Timol/farmacologia , Inibidores de beta-Lactamases/farmacologia , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Testes de Sensibilidade Microbiana
12.
Exp Parasitol ; 207: 107774, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31614118

RESUMO

The acaricidal activity of combinations of thymol, carvacrol and eugenol was evaluated on larvae and engorged females of the cattle tick Rhipicephalus microplus. The first step assessed the compounds separately, in concentrations of 3.125, 6.25, 12.5 and 25 mg/mL. Then tests were performed with the compounds combined in the ratio of 1:1 at concentrations of 3.125 and 6.25 mg/mL, along with the control group treated with the solvent (3% DMSO). In the second step, combinations were tested incorporated in a formulation at the concentration de 6.25 mg/mL, using the larval packet and adult immersion tests. The associations carvacrol + thymol (3.125 mg/mL), carvacrol + eugenol and thymol + eugenol (6.25 mg/mL) presented synergism, while the other associations had an additive effect. In the experiments with formulation, all combinations caused 100% larval mortality, but the efficacy was under 15% against engorged females. Therefore, the combinations of thymol + carvacrol (3.125 mg/mL) as well as carvacrol + eugenol and eugenol + thymol (6.25 mg/mL) had a synergistic effect on engorged females, but when incorporated in the formulation, the acaricide activity was strong against larvae but weak against engorged females.


Assuntos
Acaricidas/farmacologia , Eugenol/farmacologia , Monoterpenos/farmacologia , Rhipicephalus/efeitos dos fármacos , Timol/farmacologia , Animais , Cimenos , Combinação de Medicamentos , Sinergismo Farmacológico , Feminino , Larva/efeitos dos fármacos
13.
Vet Dermatol ; 30(6): 524-e159, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31566822

RESUMO

BACKGROUND: Multidrug-resistant pathogens present a major global challenge in antimicrobial therapy and frequently complicate otitis externa in dogs. HYPOTHESIS/OBJECTIVES: In vitro efficacy of oregano oil, thyme oil and their main phenolic constituents against bacterial and fungal isolates associated with canine otitis externa were investigated. It was hypothesized that the main phenolic components would have greater antimicrobial activity compared to the relative essential oil. METHODS AND MATERIALS: Antimicrobial susceptibility testing was performed using broth microdilution with spot-plating technique to determine minimum inhibitory and bactericidal/fungicidal concentrations (MICs, MBCs and MFCs). A time-kill kinetics assay was performed to confirm the bactericidal and fungicidal activity of the oils and their phenolic constituents. One hundred bacterial and fungal isolates, including meticillin-susceptible Staphylococcus pseudintermedius (n = 10), meticillin-resistant S. pseudintermedius (n = 10), ß-haemolytic Streptococcus spp. (n = 20), Pseudomonas aeruginosa (n = 20; including 10 isolates resistant to one or two antimicrobials), Proteus mirabilis (n = 20) and Malassezia pachydermatis (n = 20) from dogs with otitis externa were used. RESULTS: Oregano oil, thyme oil, carvacrol and thymol exhibited antibacterial activity against all bacterial and fungal isolates tested. MIC90 values ranged from 0.015 to 0.03% (146-292 µg/mL) for the Gram-positive bacteria and P. mirabilis. For P. aeruginosa and M. pachydermatis, MIC90 values ranged from 0.09 to 0.25% (800-2,292 µg/mL). CONCLUSIONS AND CLINICAL SIGNIFICANCE: Oregano oil, thyme oil, carvacrol and thymol showed good in vitro bactericidal and fungicidal activity against 100 isolates from dogs with otitis externa, including some highly drug-resistant isolates. These essential oils and their main phenolic constituents have the potential to be further investigated in vivo for the treatment of canine otitis externa.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Óleos Voláteis/farmacologia , Otite Externa/veterinária , Óleos Vegetais/farmacologia , Animais , Cimenos/farmacologia , Doenças do Cão/microbiologia , Cães , Testes de Sensibilidade Microbiana , Origanum/química , Otite Externa/microbiologia , Timol/farmacologia , Thymus (Planta)/química
14.
Plant Physiol Biochem ; 145: 64-74, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31665668

RESUMO

Herein, we report zinc-functionalized thymol nanoemulsion (Zn-TNE) by sonication method and its characterization by DLS, HR-TEM, FEG-SEM-EDS, Cryo-FESEM, FTIR and AAS studies. Zn-TNE treated seeds bestowed better seedling vigor index and higher activities of seed stored food mobilizing enzymes (α-amylase and protease). Foliar application of Zn-TNE (0.01-0.06%, v/v) enhanced defense-antioxidant enzymes activities, balanced reactive oxygen species, induced higher content of chlorophyll-a, b and higher lignin deposition in soybean plants. In the field, Zn-TNE application (0.02-0.06%, v/v) significantly controlled bacterial pustule disease (PEDC value 28-79%) and increased grain yield up to 16.6% as compared with bulk thymol application and up to 50% from control. Disease control and higher yield in soybean could be explained by diverse bioactivities of Zn-TNE in maintaining cellular homeostasis of soybean plants. Study shows that Zn-TNE can further be maneuvered for slow delivery of other micronutrients for higher crop yield.


Assuntos
Produção Agrícola , Soja , Timol , Zinco , Produção Agrícola/métodos , Sementes/efeitos dos fármacos , Soja/efeitos dos fármacos , Soja/fisiologia , Timol/farmacologia , Zinco/farmacologia
15.
J Pharm Pharmacol ; 71(12): 1774-1783, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31608449

RESUMO

OBJECTIVES: Based on this, the central therapeutic effects of thymol were verified in the neurotrophic pathway. METHODS: Female swiss mice were divided into four groups: control, corticosterone (Cort), thymol (Cort + thymol) and fluvoxamine (Cort + Flu). The administration of corticosterone was used to induce depressive symptoms for 23 days. After the treatment, the animals were exposed the behavioural tests, such as forced swimming test, tail suspension test, sucrose preference test, light/dark test, social interaction test, Y-maze test, plus-maze test and hole-board test. The hippocampus was also removed, and BDNF was measured by ELISA and Western blot. KEY FINDINGS: As a result, thymol and fluvoxamine were able to reverse the depressive symptoms, as well as to improve the anxious frame. The anhedonic and short-term memory was restored with the treatment. In the neurochemical tests, both thymol and fluvoxamine restored BDNF levels, improving the depressive condition. CONCLUSIONS: This work opens up new investigations aiming at the use of this molecule as a therapeutic alternative for treating depression disorders.


Assuntos
Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/tratamento farmacológico , Timol/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Corticosterona/administração & dosagem , Modelos Animais de Doenças , Feminino , Fluvoxamina/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Regulação para Cima/efeitos dos fármacos
16.
J Food Sci ; 84(11): 3194-3203, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31589346

RESUMO

A multilayer film containing star anise essential oil and thymol coating layers (SAEO and TH, respectively), with insect repellent and antimicrobial properties, has been developed using bar coating and adhesive lamination processes. Our previous study reported the in vitro activities of this polypropylene film (PP)/SAEO/polyethylene terephthalate film (PET)/TH/low-density polyethylene film (LDPE) multilayer film. The current study focused on demonstrating the morphological, optical, and mechanical properties of the film, and evaluating its in vivo activities when used as a bread packaging material. The developed film was 15.03% thicker and 1.86% less transparent than the control film (without active agent coating layers: PP/PET/LDPE). While the color values of the developed film were slightly different from the control film, both films appeared similar to the naked eye. The tensile strength in the developed film was somewhat lower than that of the control film, while both films had statistically comparable values for elongation at break. During storage of sliced bread packaged in the developed film, the film both deterred insects from approaching toward and impeded the growth of microorganisms in the bread. These results suggest the potential applicability of the developed film as an active food packaging material with insect repellent and antimicrobial activities. PRACTICAL APPLICATION: A multilayer film incorporated with insect repellent and antimicrobial coating layers was applied in sliced wheat bread packaging. The developed film effectively inhibited approaches of stored-product insects to packaged bread and growth of microorganisms on the bread surface. It can be used as an active food packaging material that improves the safety and shelf-life of foods.


Assuntos
Antibacterianos/química , Pão/análise , Conservação de Alimentos/métodos , Illicium/química , Repelentes de Insetos/química , Óleos Voláteis/química , Timol/química , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Pão/microbiologia , Embalagem de Alimentos/instrumentação , Conservação de Alimentos/instrumentação , Repelentes de Insetos/farmacologia , Insetos/efeitos dos fármacos , Insetos/crescimento & desenvolvimento , Óleos Voláteis/farmacologia , Óleos Vegetais/química , Óleos Vegetais/farmacologia , Polietileno/química , Polipropilenos/química , Timol/farmacologia , Triticum/química , Triticum/microbiologia
17.
Molecules ; 24(19)2019 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-31547527

RESUMO

Zika virus (ZIKV) is an emerging mosquito-borne virus of medical concern. ZIKV infection may represent a serious disease, causing neonatal microcephaly and neurological disorders. Nowadays, there is no approved antiviral against ZIKV. Several indigenous or endemic medicinal plants from Mascarene archipelago in Indian Ocean have been found able to inhibit ZIKV infection. The purpose of our study was to determine whether essential oil (EO) from Reunion Island medicinal plant Ayapana triplinervis, whose thymohydroquinone dimethyl ether (THQ) is the main component has the potential to prevent ZIKV infection in human cells. Virological assays were performed on human epithelial A549 cells infected with either GFP reporter ZIKV or epidemic viral strain. Zebrafish assay was employed to evaluate the acute toxicity of THQ in vivo. We showed that both EO and THQ inhibit ZIKV infection in human cells with IC50 values of 38 and 45 µg/mL, respectively. At the noncytotoxic concentrations, EO and THQ reduced virus progeny production by 3-log. Time-of-drug-addition assays revealed that THQ could act as viral entry inhibitor. At the antiviral effective concentration, THQ injection in zebrafish does not lead to any signs of stress and does not impact fish survival, demonstrating the absence of acute toxicity for THQ. From our data, we propose that THQ is a new potent antiviral phytocompound against ZIKV, supporting the potential use of medicinal plants from Reunion Island as a source of natural and safe antiviral substances against medically important mosquito-borne viruses.


Assuntos
Óleos Voláteis/farmacologia , Plantas Medicinais/química , Timol/análogos & derivados , Zika virus/efeitos dos fármacos , Células A549 , Animais , Humanos , Óleos Voláteis/efeitos adversos , Timol/efeitos adversos , Timol/farmacologia , Peixe-Zebra , Infecção por Zika virus/prevenção & controle
18.
Oxid Med Cell Longev ; 2019: 3173745, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31531182

RESUMO

Premature ovarian failure (POF) is a common cause of infertility in premenopausal women who are unavoidably exposed to cytotoxic therapy. Radiotherapy is one of the most effective cytotoxic treatments. However, the radiosensitivity of ovarian tissues limits its therapeutic outcome and results in the depletion of the primordial follicle and loss of fertility. Therefore, the need for an effective radioprotective therapy is evident especially when none of the current clinically used modalities for radioprotection succeeds efficiently. The present study investigated the potential radioprotective effect of carvacrol (CAR) (80 mg) or thymol (80 mg) on gamma- (γ-) irradiation-induced ovarian damage as well as their role in the cross-talk between IGF-1 and TNF-α signaling and antioxidative activity. In immature female Wister rats, a single dose of whole-body irradiation (3.2 Gy, LD20) produced considerable ovarian damage, which was evident by histopathological findings and hormonal changes. Interestingly, pretreatment with CAR or thymol significantly enhanced the follicular development and restored the anti-Mullerian hormone (AMH), E2, and FSH levels. Both essential oils improved the irradiation-mediated oxidative stress and reduction in proliferating cell nuclear antigen (PCNA) expression. Moreover, irradiated rats exhibited an inverse relationship between IGF-1 and TNF-α levels two days post irradiation, which was further inverted by the pretreatment with CAR and thymol and ought to contribute in their radioprotective mechanisms. In conclusion, CAR and thymol showed a radioprotective effect and rescued the ovarian reserve mainly through counteracting oxidative stress and the dysregulated cross-talk between IGF-1 and TNF-α.


Assuntos
Cimenos/farmacologia , Raios gama/efeitos adversos , Fator de Crescimento Insulin-Like I/metabolismo , Insuficiência Ovariana Primária/sangue , Protetores contra Radiação/farmacologia , Transdução de Sinais , Timol/farmacologia , Fator de Necrose Tumoral alfa/sangue , Animais , Feminino , Insuficiência Ovariana Primária/etiologia , Radioterapia/efeitos adversos , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação
19.
Food Chem Toxicol ; 134: 110844, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31562950

RESUMO

Mesenchymal stromal cells (MSCs) represent a progenitor cell population with several biological properties. MSCs are thus of therapeutic interest for cell-based therapy but great efforts are needed to enhance their efficiency and safety. Herbal remedies and in particular their bioactive molecules, are potential candidates for improving human health. The novelty and originality of this study is to develop an efficient cell-therapeutic product by combining MSCs with medicinal plant derived bioactive molecules. Thus, the impact of Essential Oil, Thymol and Carvacrol from Ptychotis verticillata on several BM-MSC biological features were studied. These compounds have shown positive effects on MSCs by preserving their morphology, sustaining their viability, promoting their proliferation, protecting them from cytotoxicity and oxidative stress. Accordingly, the combined administration of P. verticillata extract and MSCs may represent a new approach to enhance the therapeutic issue. Further investigations should greatly improve the manufacturing of these compounds as well as our understanding of the therapeutic effects of these bioactive molecules on the biology and functions of MSCs.


Assuntos
Cimenos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Óleos Voláteis/farmacologia , Timol/farmacologia , Proliferação de Células/efeitos dos fármacos , Humanos
20.
Drug Des Devel Ther ; 13: 2513-2532, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440034

RESUMO

Background: Nowadays, the drug delivery system is important in the treatment of diseases. Purpose: A polymeric nanoparticle modified by oleic acid (NPMO) as a Thymol (Thy) drug release system was synthesized from Thymbra spicata and its neurotrophic and angiogenic effects on rat's olfactory ensheathing cells (OECs) in normal (NG) and high glucose (HG) conditions were studied. Methods: The NPMO was characterized by using different spectroscopy methods, such as infrared, HNMR, CNMR, gel permeation chromatography, dynamic light scattering, and atomic force microscopy. Load and releasing were investigated by HPLC. The toxicity against OECs diet-induced by MTT assay. ROS and generation of nitric oxide (NO) were evaluated using dichloro-dihydro-fluorescein and Griess method, respectively. The expression of protein integrin-linked kinase (ILK), vascular endothelial growth factor (VEGF), brain-derived neurotrophic factor (BDNF), and nerve growth factor (NGF) were evaluated by Western blotting. Results: ThyNPMO is desirable for transferring drug as a carrier. The amount of Thy and extract (E) loaded on NPMO estimated at 43±2.5% and 41±1.8%, respectively. Then, 65% and 63% of the drug load were released, respectively. Thy, ThyNPMO, E, and ENPMO prevented HG-induced OECs cell death (EC50 33±1.5, 22±0.9, 35±1.8, and 25±1.1 µM, respectively). Incubation with Thy, ThyNPMO, E ,and ENPMO at high concentrations increased cell death with LC50 105±3.5, 82±2.8, 109±4.3, and 86±3.4 µM, respectively in HG states. Conclusion: OECs were protected by ThyNPMO and ENPMO in protective concentrations by reducing the amount of ROS and NO, maintaining ILK, reducing VEGF, and increasing BDNF and NGF. The mentioned mechanisms were totally reversed at high concentrations.


Assuntos
Glucose/efeitos adversos , Glucose/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Nanopartículas/química , Mucosa Olfatória/efeitos dos fármacos , Polímeros/síntese química , Proteínas Serina-Treonina Quinases/metabolismo , Timol/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Conformação Molecular , Óxido Nítrico/análise , Óxido Nítrico/biossíntese , Mucosa Olfatória/metabolismo , Polímeros/química , Polímeros/farmacologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade , Timol/síntese química , Timol/química
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