RESUMO
Otopetrin 1 (OTOP1) is a proton-activated channel crucial for animals' perception of sour taste. Despite its significance, the gating mechanism of OTOP1 remains poorly understood. Here, we demonstrate that carvacrol activates the mouse OTOP1 (mOTOP1) channel under neutral and acidic conditions. Functional analysis showed that carvacrol enhances pH fluorescence signals in OTOP1-expressing cells, with reduced efficacy at lower pH levels. Carvacrol selectively activates mOTOP1, while mOTOP2, mOTOP3, and Chelonia mydas OTOP1 (CmOTOP1) are insensitive to carvacrol activation under neutral pH. Through chimera and point mutation experiments, swapping S134 in transmembrane segment 3 (TM3) and T247 in the TM5-6 linker abolished carvacrol activation of mOTOP1 and conferred activation on CmOTOP1, suggesting these two residues are critical for carvacrol sensitivity. These findings highlight TM3 and TM5-6 linker as pivotal gating apparatus of OTOP1 channels and potential docking sites for drug design.
Assuntos
Cimenos , Cimenos/farmacologia , Animais , Camundongos , Ativação do Canal Iônico/efeitos dos fármacos , Humanos , Células HEK293 , Concentração de Íons de Hidrogênio , Canais Iônicos/metabolismo , Canais Iônicos/genéticaRESUMO
Pichia kudriavzevii (formerly Candida krusei) poses a significant threat to immunocompromised patients due to its inherent resistance to various antifungal drugs. This study explored the anticandidal potential of citral, linalool, and carvacrol in combination with nystatin against P. kudriavzevii strains.Using the microdilution method following CLSI guidelines, Minimum Inhibitory Concentrations (MICs) and fungicidal concentrations (MFCs) were determined. Citral exhibited MIC values ranging from 50 to 100 µg/ml, averaging 70.24 ± 16.99 µg/ml, while carvacrol had MIC values of 50 to 100 µg/ml, averaging 86.90 ± 16.99 µg/ml. Linalool demonstrated weaker antifungal activity, with MIC values between 100 and 200 µg/ml, averaging 150 ± 38.73 µg/ml. The study assessed the synergistic effectsof these phenols with nystatin through fractional inhibitory concentration indices (FICIS). In addition, flow cytometry was employed to assess apoptosis induction in P. kudriavzevii cells.Carvacrol displayed a remarkable synergistic effect in combination with nystatin against all 21 isolates tested. Conversely, linalool showed synergy in 17 isolates, while citral exhibited synergy in only 2 isolates. These findings highlight distinct patterns of synergy between the different compounds and nystatin against P. kudriavzevii. Also, Carvacrol emerged as the most potent inducer of apoptosis across all P. kudriavzevii strains, followed by citral and linalool. This suggests that carvacrol not only possesses a stronger antifungal effect but also has a more pronounced ability to trigger programmed cell death in P. kudriavzevii. In conclusion, the study supports the potential of carvacrol, citral and linalool, as anticandidal agents, suggesting their supplementation with nystatin for treating P. kudriavzevii infections.
Assuntos
Monoterpenos Acíclicos , Antifúngicos , Apoptose , Cimenos , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana , Monoterpenos , Nistatina , Pichia , Antifúngicos/farmacologia , Cimenos/farmacologia , Monoterpenos Acíclicos/farmacologia , Nistatina/farmacologia , Apoptose/efeitos dos fármacos , Humanos , Monoterpenos/farmacologia , Pichia/efeitos dos fármacos , Pichia/isolamento & purificaçãoRESUMO
This study aimed to investigate the effects of the monoterpenes thymol and p-cymene on the liver of rats subjected to prolonged immobilization stress and to discover the possible mechanism behind this effect. For 14 consecutive days, the rats were placed in a restrainer for 2.5 h every day to expose them to stress. During the same period, thymol (10 mg/kg, gavage) and p-cymene (50 mg/kg, intraperitoneally) were also administered. Thymol and p-cymene prevented the increase in malondialdehyde levels and the decrease in glutathione content in the liver of rats exposed to chronic immobility. They also increased the activity of the glutathione peroxidase enzyme in the liver of stressed animals, but only thymol could increase the activity of superoxide dismutase. These monoterpenes reduced the expression of pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, and IL-6 and nuclear factor kappa B (NF-κB) in the liver of stressed animals. They increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Thymol and p-cymene greatly prevented the infiltration of inflammatory cells in the liver parenchyma of stressed rats. In conclusion, the study found that thymol and p-cymene have a hepatoprotective effect on immobilized rats, likely exerted by suppressing oxidative stress and inflammation, stimulating Nrf2/HO-1 signaling, and inhibiting the TNF-α/NF-κB pathway.
Assuntos
Cimenos , Fígado , Monoterpenos , Fator 2 Relacionado a NF-E2 , NF-kappa B , Estresse Oxidativo , Timol , Fator de Necrose Tumoral alfa , Animais , Cimenos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , NF-kappa B/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Ratos , Fator de Necrose Tumoral alfa/metabolismo , Timol/farmacologia , Masculino , Monoterpenos/farmacologia , Ratos Wistar , Heme Oxigenase-1/metabolismo , Malondialdeído/metabolismo , Imobilização , Superóxido Dismutase/metabolismo , Glutationa/metabolismo , Heme Oxigenase (Desciclizante)RESUMO
OBJECTIVES: This study aimed to investigate the protective effect and mechanism of carvacrol hydrogel on the alveolar bone in rats with periodontitis. METHODS: A thermosensitive hydrogel supported by carvacrol was prepared using poloxamer and hydroxypropyl methyl cellulose as matrix. SD rats were randomly divided into blank group, periodontitis group, blank hydrogel group, and low-, medium-, and high-dose hydrogel groups. The periodontitis symptoms and the CT structure of the alveolar bone were observed. The changes in liver, spleen, kidney, and periodontal tissues were observed. The related indexes of bone metabolism in serum were detected. The expression of osteoprotegerin (OPG) and nuclear transcription factor-κB (NF-κB) pathway proteins was determined by Western blot. The levels of inflammatory factors were assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Carvacrol hydrogel had good slow release, biocompatibility, and cell adhesion. The periodontitis of rats in the carvacrol hydrogel group was significantly alleviated, the expression of OPG protein in gingival tissue was significantly increased (P<0.01), and the levels of receptor activator of NF-κB ligand (RANKL), receptor activator of NF-κB (RANK), NF-κB protein, and inflammatory factors were significantly decreased (P<0.01). CONCLUSIONS: Carvacrol hydrogel can regulate the OPG and NF-κB pathways, reduce alveolar bone absorption, and improve periodontal inflammation.
Assuntos
Cimenos , Hidrogéis , NF-kappa B , Osteoprotegerina , Periodontite , Ratos Sprague-Dawley , Animais , Cimenos/farmacologia , Cimenos/uso terapêutico , Ratos , Periodontite/tratamento farmacológico , Osteoprotegerina/metabolismo , NF-kappa B/metabolismo , Processo Alveolar/efeitos dos fármacos , Processo Alveolar/metabolismo , Monoterpenos/farmacologia , Monoterpenos/uso terapêuticoRESUMO
The skin is constantly exposed to a variety of environmental stressors, including ultraviolet (UV) radiation. Exposure of the skin to UV radiation causes a number of detrimental biological damages such as endoplasmic reticulum (ER) stress. The ER stress response is a cytoprotective mechanism that maintains homeostasis of the ER by increasing the capacity of the ER against the accumulation of unfolded proteins in the ER. Carvacrol (CRV) is a monoterpenoid phenol found in essential oils with antimicrobial and anti-inflammatory activities. We investigated for the first time in the literature the potential protective role of CRV against combined UVA and UVB-induced skin damage by targeting the ER stress pathway in a rat model. For this purpose, expressions of Grp78, Perk, Atf6, Ire-1, Chop, Xbp1, Casp12, elF2α, and Traf2 genes related to ER stress were analyzed by RT-PCR and protein expression levels of GRP78, ATF6, CHOP, and XBP1 were determined by ELISA assay in tissue sections taken from the back of the rats. As a result of analysis, it was seen that the expression levels of aforementioned ER stress genes increased significantly in the UVA + UVB irradiated group compared to the control group, while their expression levels decreased markedly by supplementation of CRV in UVA + UVB + CRV group. With regard to expressions of foregoing proteins, their levels escalated notably with UVA + UVB application and decreased markedly by CRV supplementation. In conclusion, present study revealed that CRV ameliorates UVA + UVB-induced ER stress via reducing the expression of mRNA as well as proteins involved in the unfolded protein response (UPR) pathway and inducing apoptosis as evidenced from high Caspase12 level.
Assuntos
Cimenos , Estresse do Retículo Endoplasmático , Raios Ultravioleta , Animais , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Raios Ultravioleta/efeitos adversos , Cimenos/farmacologia , Ratos , Pele/efeitos dos fármacos , Pele/patologia , Pele/efeitos da radiação , Pele/metabolismo , Monoterpenos/farmacologia , Monoterpenos/química , Masculino , Ratos WistarRESUMO
Oral submucous fibrosis (OSF) is a precancerous condition in the oral cavity, which is closely related to the myofibroblast conversion of buccal mucosal fibroblasts (BMFs) after chronic consumption of areca nut. Emerging evidence suggests pyroptosis, a form of programmed cell death that is mediated by inflammasome, is implicated in persistent myofibroblast activation and fibrosis. Besides, numerous studies have demonstrated the effects of non-coding RNAs on pyroptosis and myofibroblast activities. Herein, we aimed to target key long non-coding RNA PVT1 with natural compound, carvacrol, to alleviate pyroptosis and myofibroblast activation in OSF. We first identified PVT1 was downregulated in the carvacrol-treated fBMFs and then demonstrated that myofibroblast features and expression of pyroptosis makers were all reduced in response to carvacrol treatment. Subsequently, we analysed the expression of PVT1 and found that PVT1 was aberrantly upregulated in OSF specimens and positively correlated with several fibrosis markers. After revealing the suppressive effects of carvacrol on myofibroblast characterisitcs and pyroptosis were mediated by repression of PVT1, we then explored the potential mechanisms. Our data showed that PVT1 may serve as a sponge of microRNA(miR)-20a to mitigate the myofibroblast activation and pyroptosis. Altogether, these findings indicated that the anti-fibrosis effects of carvacrol merit consideration and may be due to the attenuation of pyroptosis and myofibroblast activation by targeting the PVT1/miR-20a axis.
Assuntos
Cimenos , MicroRNAs , Miofibroblastos , Fibrose Oral Submucosa , Piroptose , RNA Longo não Codificante , Fibrose Oral Submucosa/patologia , Fibrose Oral Submucosa/genética , Fibrose Oral Submucosa/metabolismo , Fibrose Oral Submucosa/tratamento farmacológico , Piroptose/efeitos dos fármacos , Piroptose/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Humanos , Cimenos/farmacologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Miofibroblastos/metabolismo , Miofibroblastos/efeitos dos fármacos , Miofibroblastos/patologia , Progressão da Doença , Regulação para Baixo/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/efeitos dos fármacosRESUMO
Arsenic is a toxic environmental pollutant heavy metal, and one of its critical target tissues in the body is the liver. Carvacrol is a natural phytocompound that stands out with its antioxidant, anti-inflammatory, and antiapoptotic properties. The current study aims to investigate the protective feature of carvacrol against sodium arsenite-induced liver toxicity. Thirty-five Sprague-Dawley male rats were divided into five groups: Control, Sodium arsenite (SA), CRV, SA + CRV25, and SA + CRV50. Sodium arsenite was administered via oral gavage at a dose of 10 mg/kg for 14 days, and 30 min later, CRV 25 or 50 mg/kg was administered via oral gavage. Oxidative stress, inflammation, apoptosis, autophagy damage pathways parameters, and liver tissue integrity were analyzed using biochemical, molecular, western blot, histological, and immunohistological methods. Carvacrol decreased sodium arsenite-induced oxidative stress by suppressing malondialdehyde levels and increasing superoxide dismutase, catalase, glutathione peroxidase activities, and glutathione levels. Carvacrol reduced inflammation damage by reducing sodium arsenite-induced increased levels of NF-κB and the cytokines (TNF-α, IL-1ß, IL-6, RAGE, and NLRP3) it stimulates. Carvacrol also reduced sodium arsenite-induced autophagic (Beclin-1, LC3A, and LC3B) and apoptotic (P53, Apaf-1, Casp-3, Casp-6, Casp-9, and Bax) parameters. Carvacrol preserved sodium arsenite-induced impaired liver tissue structure. Carvacrol alleviated toxic damage by reducing sodium arsenite-induced increases in oxidative stress, inflammation, apoptosis, and autophagic damage parameters in rat liver tissues. Carvacrol was also beneficial in preserving liver tissue integrity.
Assuntos
Arsenitos , Caspase 3 , Doença Hepática Induzida por Substâncias e Drogas , Cimenos , Fator 2 Relacionado a NF-E2 , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos Sprague-Dawley , Compostos de Sódio , Animais , Masculino , Ratos , Compostos de Sódio/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cimenos/farmacologia , Arsenitos/toxicidade , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Caspase 3/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Proteína Beclina-1/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Proteína X Associada a bcl-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Estresse Oxidativo/efeitos dos fármacosRESUMO
Tribolium castaneum is a challenging pest of stored products, causing significant economic losses. The present study explored the efficacy of Coridothymus capitatus essential oil and its primary constituent, carvacrol, as eco-friendly alternatives for managing this pest. To evaluate their insecticidal potential, repellency, fumigant toxicity, and antifeedant properties, progeny inhibition assays were performed. Carvacrol exhibited superior repellency compared to the essential oil, achieving a 92% repellency rate at 2 mg/cm2. Both compounds demonstrated significant fumigant toxicity against T. castaneum, with LC50 values of 168.47 and 106.5 µL/L for the essential oil and carvacrol, respectively, after 24 h. Carvacrol also outperformed the essential oil in antifeedant activity, inducing an 80.7% feeding deterrence at 1.17 mg/g. Moreover, both treatments effectively suppressed the development of the pest's progeny. These results collectively underscore the potent insecticidal properties of C. capitatus essential oil and carvacrol, particularly carvacrol, as promising candidates for the sustainable management of T. castaneum in stored product protection.
Assuntos
Cimenos , Repelentes de Insetos , Inseticidas , Óleos Voláteis , Tribolium , Animais , Cimenos/farmacologia , Repelentes de Insetos/farmacologia , Repelentes de Insetos/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Inseticidas/farmacologia , Inseticidas/química , Tribolium/efeitos dos fármacos , Fumigação , Besouros/efeitos dos fármacosRESUMO
This work aimed to explore an alternative to the use of antibiotics for prevention and treatment of wounds infection caused by two common bacterial pathogens Staphylococcus aureus and Pseudomonas aeruginosa. For this purpose, three different essential oil components (EOCs), namely carvacrol, citronellol and cinnamic acid, were loaded into electrospun fibers of poly-ε-caprolactone (PCL) aided by alpha-cyclodextrin (αCD) and hydroxypropyl-ß-cyclodextrin (HPßCD). Electrospun-fibers prepared with each EOC and their mixtures were screened for antimicrobial capability and characterized regarding morphological, mechanical, thermal, surface polarity, antibiofilm and antioxidant properties. αCD formed poly(pseudo)rotaxanes with PCL and weakly interacted with EOCs, while HPßCD facilitated EOC encapsulation and formation of homogeneous fibers (500-1000 nm diameter) without beads. PCL/HPßCD fibers with high concentration of EOCs (mainly carvacrol and cinnamic acid) showed strong antibiofilm (>3 log CFU reduction) and antioxidant activity (10-50% DPPH scavenging effects). Different performances were recorded for the EOCs and their mixtures; cinnamic acid migrated to fiber surface and was released faster. Fibers biocompatibility was verified using hemolysis tests and in ovo tissue integration and angiogenesis assays. Overall, HPßCD facilitates complete release of EOCs from the fibers to the aqueous medium, being an environment-friendly and cost-effective strategy for the treatment of infected wounds.
Assuntos
Monoterpenos Acíclicos , Antioxidantes , Cinamatos , Cimenos , Monoterpenos , Cicatrização , Cicatrização/efeitos dos fármacos , Cimenos/farmacologia , Cimenos/química , Cinamatos/química , Cinamatos/farmacologia , Monoterpenos Acíclicos/farmacologia , Monoterpenos Acíclicos/química , Antioxidantes/farmacologia , Antioxidantes/química , Monoterpenos/farmacologia , Monoterpenos/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Staphylococcus aureus/efeitos dos fármacos , Ciclodextrinas/química , Ciclodextrinas/farmacologia , Biofilmes/efeitos dos fármacos , Nanofibras/química , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologia , Antibacterianos/química , Poliésteres/química , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Pseudomonas aeruginosa/efeitos dos fármacosRESUMO
Natural caffeic acid (CA) and its analogues have been studied for their potential applications in the treatment of various inflammatory and infectious skin diseases. However, the molecular mechanism underlying the effects of the CA remains largely unknown. Here, we report that CA and its two analogues, caffeic acid phenethyl ester (CAPE) and caffeic acid methyl caffeate (CAMC), inhibit TRPV3 currents in their concentration- and structure-dependent manners with IC50 values ranging from 102 to 410 µM. At the single-channel level, CA reduces the channel open probability and open frequency without alteration of unitary conductance. CA selectively inhibits TRPV3 relative to other subtypes of thermo-TRPs, such as TRPA1, TRPV1, TRPV4, and TRPM8. Molecular docking combined with site-specific mutagenesis reveals that a residue T636 in the Pore-loop is critical for CA binding to TRPV3. Further in vivo evaluation shows that CA significantly reverses TRPV3-mediated skin inflammation induced by skin sensitizer carvacrol. Altogether, our findings demonstrate that CA exerts its anti-inflammatory effects by selectively inhibiting TRPV3 through binding to the pocket formed by the Pore-loop and the S6. CA may serve as a lead for further modification and identification of specific TRPV3 channel inhibitors.
Assuntos
Ácidos Cafeicos , Simulação de Acoplamento Molecular , Canais de Cátion TRPV , Ácidos Cafeicos/farmacologia , Ácidos Cafeicos/química , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/antagonistas & inibidores , Humanos , Animais , Camundongos , Pele/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Cimenos/farmacologia , Cimenos/química , Células HEK293 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Inflamação/tratamento farmacológico , Inflamação/metabolismoRESUMO
The adherence of foodborne microorganisms threatens human health, necessitating the development of antibacterial food packaging films. In this study, the antibacterial agent carvacrol (CV), hindered by its high volatility and intense aromatic odor, was encapsulated within the photosensitive metal-organic frameworks (MOFs) material PCN-224 (loading rate 50%). Subsequently, the microfluidic-blow-spinning (MBS) technique was employed for the rapid fabrication of CV@PCN-224/polycaprolactone (PCL)/chitosan (CS) nanofiber films. The incorporation of CV@PCN-224 NPs enhances the nanofiber films' thermal stability and mechanical properties and improves the water vapor permeability while maintaining the sustained release of CV over an extended period and good biocompatibility. Due to the simultaneous loading of antibacterial agent (CV) and photosensitive agent (PCN-224), the CV@PCN-224/PCL/CS films exhibited good synergistic antibacterial functionality, as demonstrated by effective inhibition against both E. coli and S. aureus. All results show the vast potential of the prepared nanofiber films in antibacterial food packaging.
Assuntos
Antibacterianos , Cimenos , Escherichia coli , Embalagem de Alimentos , Estruturas Metalorgânicas , Nanofibras , Staphylococcus aureus , Embalagem de Alimentos/instrumentação , Cimenos/química , Cimenos/farmacologia , Nanofibras/química , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Porfirinas/química , Porfirinas/farmacologia , Microfluídica , Testes de Sensibilidade MicrobianaRESUMO
An ultrasound-assisted dispersive liquid-liquid microextraction by solidifying floating organic droplets, coupled to a form of temperature-programmed gas chromatography flame ionization detection, has been developed for the extraction and determination of thymol and carvacrol. This method utilizes undecanol as the extraction solvent, offering advantages such as facilitating phase transfer through solidification and enhancing solvent-focusing efficiency. The optimal gas chromatography conditions include a sample injection volume of 0.2 µL, a split ratio of 1:10, and a flow rate of 0.7 mL min-1. The extraction conditions entail an extraction solvent volume of 20 µL, a disperser solvent (acetone) volume of 500 µL, pH 7.0, 7.0% NaCl (3.5 M), a sample volume of 5.0 mL, an ultrasound duration of 10 min, and a centrifuge time of 7.5 min (800 rpm). These conditions enable the achievement of a high and reasonable linear range of 3.5 to 70. 0 µg mL-1 for both thymol and carvacrol. The detection limits are found to be 0.95 and 0.89 µg mL-1, respectively, for thymol and carvacrol. The obtained relative standard deviations, 2.7% for thymol and 2.6% for carvacrol, demonstrate acceptable precision for the purpose of quantitative analysis.
Assuntos
Cimenos , Microextração em Fase Líquida , Solventes , Timol , Timol/análise , Timol/química , Cimenos/química , Cimenos/análise , Microextração em Fase Líquida/métodos , Cromatografia Gasosa/métodos , Solventes/química , Limite de DetecçãoRESUMO
Carvacrol and thymol are broad-spectrum natural antimicrobial agents. To reduce their volatility and improve their antimicrobial performance, synergistic systems were prepared loading the active molecules in zinc-modified clays. Montmorillonite (MMT) and zeolite (ZEO) were modified with zinc ions (ZnMMT and ZnZEO), with well-known antimicrobial properties, and then with carvacrol or thymol, reaching the 26 ± 3% and 33 ± 2% w/w of loading, respectively. The resulting hybrid materials were characterized by FT-IR, XPS, XRD, TGA, and GC-MS to evaluate carvacrol/thymol release in simulating food matrices. Antimicrobial assays carried out using spoiler and pathogenic bacterial strains showed that the antimicrobial activity of both thymol and carvacrol was largely preserved once they were loaded into Zn-modified clays. However, MMT hybrids showed an antibacterial activity significantly higher than ZEO hybrids at 50 mg/mL of thymol and carvacrol. For this reason, deeper antimicrobial evaluations were carried out only for ZnMMT composites. ZnMMT loaded with thymol or carvacrol produced inhibition zones against most of the target strains, also at 3.12 mg/mL, while the positive controls represented by the single molecule thymol or carvacrol were not active. The hybrid materials can be useful for applications in which the antimicrobial activity of natural molecules need to be displayed over time as requested for the control of microbial pathogens and spoilage bacteria in different applications, such as active packaging, biomaterials, and medical devices.
Assuntos
Anti-Infecciosos , Argila , Cimenos , Testes de Sensibilidade Microbiana , Timol , Zinco , Cimenos/química , Cimenos/farmacologia , Timol/química , Timol/farmacologia , Zinco/química , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Argila/química , Espectroscopia de Infravermelho com Transformada de Fourier , Bactérias/efeitos dos fármacos , Bentonita/químicaRESUMO
In the current study, to discover novel antibacterial agents, we designed and synthesized 72 carvacrol and thymol derivatives by biomimicking the structure and function of cationic antimicrobial peptides (AMPs). Many of the derivatives showed good antibacterial activity, and compound thy2I exhibited the most potent antibacterial activity with minimum inhibitory concentration (MIC) values ranging from 0.5 µg/mL to 8 µg/mL. Compound thy2I could kill both gram-positive and gram-negative bacteria via a membrane-targeting mechanism of action with a low frequency of resistance. In addition, thy2I had the advantages of good membrane selectivity, low toxicity in vitro and in vivo, and good plasma stability. The in vivo activity results revealed that thy2I exhibited a positive therapeutic effect in a mouse skin abscess model induced by Staphylococcus aureus ATCC29213. After thy2I treatment (10 mg/kg), the bacterial load of the S. aureus-infected abscesses was reduced by approximately 99.65 %. Our study suggests that thy2I may serve as an antibacterial lead for further clinical evaluation.
Assuntos
Antibacterianos , Cimenos , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Timol , Cimenos/farmacologia , Cimenos/química , Timol/farmacologia , Timol/química , Timol/síntese química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Animais , Camundongos , Relação Estrutura-Atividade , Staphylococcus aureus/efeitos dos fármacos , Estrutura Molecular , Relação Dose-Resposta a Droga , Bactérias Gram-Negativas/efeitos dos fármacosRESUMO
The incorporation of active compounds into polymeric matrices using traditional methods has several drawbacks mainly due to the high volatility and thermal sensitivity of these substances. A solution to this problem could be the incorporation of bioactive compounds forming inclusion complexes as a strategy to improve the chemical stability, bioactivity and achieve controlled release. In this work, ß-cyclodextrin/carvacrol inclusion complex was prepared by spray drying to be incorporated into poly(lactic acid) (PLA) and Mater-Bi® films by supercritical CO2 impregnation. The impregnation process was carried out at pressures of 10, 15 and 20â¯MPa and at 40⯰C. Both polymers showed the highest amount of incorporated inclusion complex at 15â¯MPa, where the percentage of impregnation varied from 0.6â¯% to 7.1â¯% in Mater-Bi® and PLA, respectively. Release tests for PLA films impregnated with inclusion complex showed a slow release of the active compound, which did not reach equilibrium after 350â¯h under the experimental conditions. This prolonged release was not observed in Mater-Bi® due to the lower incorporation of the inclusion complex. The release rate was described herein by a comprehensive phenomenological model considering the decomplexation kinetics combined with the equilibrium and mass transfer expressions.
Assuntos
Cimenos , Poliésteres , beta-Ciclodextrinas , Poliésteres/química , beta-Ciclodextrinas/química , Cimenos/química , Cinética , Liberação Controlada de FármacosRESUMO
Soy isolate protein / chitooligosaccharide (SPI/COS) glycosylated conjugates was prepared and employed as an emulsifier to stabilize carvacrol-loaded nanoemulsions (CNE-SPI/COS). The effects of CNE-SPI/COS on the oxidation and aggregation of myofibrillar protein (MPs) from sea bass (Lateolabrax maculatus) were investigated. Samples were immersed in sterile water (CK), SPI/COS solution and CNE-SPI/COS solution, respectively, follow by a 15-day refrigerated storage. MPs were extracted from fish fillets at 3-day intervals, then assessed for the oxidation degree and conformational changes in MPs, as well as structural variations in myofibrils. Compared with the CK group, the results obtained from protein oxidation assessment clarified that the oxidation and aggregation of MPs was significantly reduced by the CNE-SPI/COS treatment, as evidenced by the higher total sulfhydryl content and Ca2+-ATPase activity and lower surface hydrophobicity. Conformational analysis of MPs showed that CNE-SPI/COS was effective in maintaining the ordered secondary structure of MPs and reducing the exposure of hydrophobic residues in the hydrophobic core of the tertiary structure. In addition, CNE-SPI/COS was found to be effective in protecting the microstructure of muscle fibers and myofibrils in fish fillets. These results suggest that CNE-SPI/COS can be a promising method to prevent protein oxidation and aggregation in fish.
Assuntos
Bass , Cimenos , Emulsões , Proteínas de Peixes , Oxirredução , Proteínas de Soja , Animais , Bass/metabolismo , Emulsões/química , Cimenos/química , Cimenos/farmacologia , Proteínas de Peixes/química , Proteínas de Soja/química , Proteínas de Soja/metabolismo , Proteínas Musculares/química , Proteínas Musculares/metabolismo , Oligossacarídeos/química , Quitosana/química , Quitina/química , Quitina/análogos & derivados , Miofibrilas/química , Miofibrilas/metabolismo , Alimentos Marinhos/análise , Conservação de Alimentos , Conformação Proteica , RefrigeraçãoRESUMO
OBJECTIVES: This study compares the biofilm inhibition effects of denture cleaning tablets, carvacrol, and their combined use against Candida albicans on denture bases produced with different techniques. Additionally, the surface roughness and contact angles of these denture bases were evaluated. MATERIALS AND METHODS: Test samples were prepared from four different denture base materials (cold-polymerized, heat-polymerized, CAD/CAM milling, and 3D-printed). The surface roughness and contact angles of the test samples were measured using a profilometer and goniometer, respectively. For the evaluation of biofilm inhibition, samples were divided into 5 subgroups: Corega and carvacrol, separately and combined treatments, positive (inoculated with C. albicans) and negative control (non-inoculated with C. albicans, only medium). Biofilm mass was determined using the crystal violet method. An additional prepared test sample for each subgroup was examined under scanning electron microscopy (SEM). RESULTS: The surface roughness values of the 3D-printed test samples were found to be statistically higher than the other groups (P < .001). The water contact angle of all test materials was not statistically different from each other (P > .001). Corega and carvacrol, separately and combined, significantly decreased the amount of biofilm on all surfaces (P < .0001). Treatment of corega alone and in combination with carvacrol to the 3D-printed material caused less C. albicans inhibition than the other groups (P < .001; P < .05). CONCLUSIONS: The surface roughness values of all test groups were within the clinically acceptable threshold. Although Corega and carvacrol inhibited C. albicans biofilms, their combined use did not show a synergistic effect. CLINICAL RELEVANCE: Carvacrol may be used as one of the disinfectant agents for denture cleaning due to its biofilm inhibition property.
Assuntos
Biofilmes , Candida albicans , Cimenos , Bases de Dentadura , Higienizadores de Dentadura , Teste de Materiais , Microscopia Eletrônica de Varredura , Propriedades de Superfície , Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Bases de Dentadura/microbiologia , Cimenos/farmacologia , Higienizadores de Dentadura/farmacologia , Impressão Tridimensional , ComprimidosRESUMO
BACKGROUND: The Pseudorabies Virus (PRV) leading to pseudorabies and causes huge economic losses in pig industry. The development of novel PRV variations has diminished the efficacy of traditional vaccinations, and there is yet no medication that can stop the spread of PRV infection. Therefore, PRV eradication is challenging. Oregano essential oil, the plant-based ingredient for medication feed have been shown to has strong anti-herpesvirus activity, but no anti-PRV function has been reported. RESULTS: The current study assessed the anti-pseudorabies virus (PRV) activity of oregano essential oil and explored its mechanisms and most effective components against PRV. Our in vivo findings demonstrated that oregano essential oil could decrease the PRV load in tissues, mitigate tissue lesions, and enhance the survival rate of mice. The potential antiviral mechanism involves augmenting humoral and cellular immune responses in PRV-infected mice. To further investigate the most effective components of oregano essential oil against PRV, an in vitro study was conducted, revealing that oregano essential oil and its main constituents, carvacrol and thymol, all diminished PRV intracellular proliferation in vitro. Carvacrol exhibited the most potent anti-PRV effect, serving as the primary contributor to oregano essential oil's anti-PRV activity. The mechanisms underlying carvacrol's anti-PRV properties include the upregulation of cytokines TNF-α, IFN-ß, IFN-γ, IL-12, and the inhibition of PRV-induced apoptosis in BHK-21 cells. CONCLUSIONS: Our study provides an effective drug for the prevention and control of PRV infection.
Assuntos
Antivirais , Herpesvirus Suídeo 1 , Óleos Voláteis , Origanum , Pseudorraiva , Animais , Óleos Voláteis/farmacologia , Origanum/química , Camundongos , Herpesvirus Suídeo 1/efeitos dos fármacos , Antivirais/farmacologia , Pseudorraiva/tratamento farmacológico , Pseudorraiva/virologia , Cimenos/farmacologia , Timol/farmacologia , Citocinas/metabolismo , Linhagem Celular , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Feminino , Camundongos Endogâmicos BALB C , Carga Viral/efeitos dos fármacos , Suínos , Modelos Animais de Doenças , Óleos de Plantas/farmacologiaRESUMO
Listeria monocytogenes (L. monocytogenes) is a prevalent foodborne pathogen with a remarkable capacity to form biofilms on utensil surfaces. The Listeriolysin O (LLO) exhibits hemolytic activity, which is responsible for causing human infections. In this study, we investigated the inhibitory effect and mechanism of oregano essential oil (OEO) on L. monocytogenes, evaluated the effects on its biofilm removal and hemolytic activity. The minimum inhibitory concentration (MIC) of OEO against L. monocytogenes was 0.03 % (v/v). L. monocytogenes was treated with OEO at 3/2 MIC for 30 min the bacteria was decreased below the detection limit (10 CFU/mL) in PBS and TSB (the initial bacterial load was about 6.5 log CFU/mL). The level of L. monocytogenes in minced pork co-cultured with OEO (15 MIC) about 2.5 log CFU/g lower than that in the untreated group. The inhibitory mechanisms of OEO against planktonic L. monocytogenes encompassed perturbation of cellular morphology, elevation in reactive oxygen species levels, augmentation of lipid oxidation extent, hyperpolarization of membrane potential, and reduction in intracellular ATP concentration. In addition, OEO reduced biofilm coverage on the surface of glass slides by 62.03 % compared with the untreated group. Meanwhile, OEO (1/8 MIC) treatment reduced the hemolytic activity of L. monocytogenes to 24.6 % compared with the positive control. Molecular docking suggested carvacrol and thymol might reduce the hemolytic activity of L. monocytogenes. The results of this study demonstrate that OEO exhibits inhibitory effects against L. monocytogenes, biofilms and LLO, which had potential as natural antimicrobial for the inhibition of L. monocytogenes.
Assuntos
Antibacterianos , Toxinas Bacterianas , Biofilmes , Proteínas Hemolisinas , Listeria monocytogenes , Testes de Sensibilidade Microbiana , Óleos Voláteis , Origanum , Espécies Reativas de Oxigênio , Listeria monocytogenes/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Origanum/química , Proteínas Hemolisinas/metabolismo , Proteínas Hemolisinas/antagonistas & inibidores , Proteínas Hemolisinas/farmacologia , Toxinas Bacterianas/metabolismo , Toxinas Bacterianas/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Antibacterianos/farmacologia , Animais , Proteínas de Choque Térmico/metabolismo , Hemólise/efeitos dos fármacos , Suínos , Trifosfato de Adenosina/metabolismo , Potenciais da Membrana/efeitos dos fármacos , Simulação de Acoplamento Molecular , CimenosRESUMO
Fleagrass, a herb known for its pleasant aroma, is widely used as a mosquito repellent, antibacterial agent, and for treating colds, reducing swelling, and alleviating pain. The antifungal effects of the essential oils of fleagrass and carvacrol against Candida albicans were investigated by evaluating the growth and the mycelial and biofilm development of C. albicans. Transmission electron microscopy was used to evaluate the integrity of the cell membrane and cell wall of C. albicans. Fleagrass exhibited high fungicidal activity against C. albicans at concentrations of 0.5% v/v (via the Ras1/cAMP/PKA pathway). Furthermore, transmission electron microscopy revealed damage to the cell wall and membrane after treatment with the essential oil, which was further confirmed by the increased levels of ß-1,3-glucan and chitin in the cell wall. This study showed that fleagrass exerts good fungicidal and hyphal growth inhibition activity against C. albicans by disrupting its cell wall, and thus, fleagrass may be a potential antifungal drug.