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1.
J Ovarian Res ; 14(1): 126, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579761

RESUMO

BACKGROUND: Infections by the SARS-CoV-2 virus causing COVID-19 are presently a global emergency. The current vaccination effort may reduce the infection rate, but strain variants are emerging under selection pressure. Thus, there is an urgent need to find drugs that treat COVID-19 and save human lives. Hence, in this study, we identified phytoconstituents of an edible vegetable, Bitter melon (Momordica charantia), that affect the SARS-CoV-2 spike protein. METHODS: Components of Momordica charantia were tested to identify the compounds that bind to the SARS-CoV-2 spike protein. An MTiOpenScreen web-server was used to perform docking studies. The Lipinski rule was utilized to evaluate potential interactions between the drug and other target molecules. PyMol and Schrodinger software were used to identify the hydrophilic and hydrophobic interactions. Surface plasmon resonance (SPR) was employed to assess the interaction between an extract component (erythrodiol) and the spike protein. RESULTS: Our in-silico evaluations showed that phytoconstituents of Momordica charantia have a low binding energy range, -5.82 to -5.97 kcal/mol. A docking study revealed two sets of phytoconstituents that bind at the S1 and S2 domains of SARS-CoV-2. SPR showed that erythrodiol has a strong binding affinity (KD = 1.15 µM) with the S2 spike protein of SARS-CoV-2. Overall, docking, ADME properties, and SPR displayed strong interactions between phytoconstituents and the active site of the SARS-CoV-2 spike protein. CONCLUSION: This study reveals that phytoconstituents from bitter melon are potential agents to treat SARS-CoV-2 viral infections due to their binding to spike proteins S1 and S2.


Assuntos
Tratamento Farmacológico da COVID-19 , Momordica charantia/química , Extratos Vegetais/farmacologia , Glicoproteína da Espícula de Coronavírus/genética , Sítios de Ligação/efeitos dos fármacos , COVID-19/genética , COVID-19/virologia , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Simulação de Acoplamento Molecular , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Extratos Vegetais/química , Ligação Proteica/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/patogenicidade , Glicoproteína da Espícula de Coronavírus/antagonistas & inibidores , Ressonância de Plasmônio de Superfície
2.
Sci Rep ; 11(1): 12599, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34131254

RESUMO

In the present study, probiotic potato chips containing a newly isolated probiotic Lactococcus lactis KUMS-T18 strain were produced by using a simple spraying method and then enhancing the stability, survival rate, and sensory characteristics of product during storage at 4 °C and 25 °C was examined for four months. Based on the results, Lactococcus lactis KUMS-T18 isolated from traditional Tarkhineh as a safe strain had high tolerance to low pH and high bile salt, anti-pathogenic activity, hydrophobicity, adhesion to human epithelial cells, auto- and co-aggregation, cholesterol assimilation and antibiotic susceptibility. Meanwhile, by micro-coating the probiotic cells in Tarkhineh formulations, elliptical to spherical shape (460-740 µm) probiotic drops were produced. The results revealed that potato chips produced with turmeric and plain Tarkhineh during storage at 4 °C, had excellent protection abilities for probiotic cells with about 4.52 and 3.46 log decreases in CFU/g respectively. On the other hand, probiotic potato chips, compared to non-probiotic and commercial potato chips, showed the criteria of probiotic products such as excellent quality and superior sensory characteristics. In summary, this study proved that probiotic Lactococcus lactis KUMS-T18 strain covered by Tarkhineh formulations as protective matrix has high potential to be used in the production of probiotic potato chips.


Assuntos
Lactococcus lactis/química , Probióticos/química , Animais , Ácidos e Sais Biliares , Composição de Medicamentos , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Probióticos/farmacologia , Solanum tuberosum/química
3.
PLoS One ; 15(1): e0227979, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31995599

RESUMO

Techno-biofunctional characteristics of nanoemulsion and (nano)emulgel loaded with mangostin extracts were elucidated. Crude mangostins from mangosteen peels recovered by virgin coconut oil (VCO), mixed VCO and propylene glycol (PG), and pure PG were used. The extracts were loaded in the dispersed phase in the presence of mixed surfactants (Tween20/Span20) with a varying hydrophilic-lipophilic balance (HLB) from 10.2 to 15.1. Results showed that globular and uniformly distributed droplets of the nanoemulsion were observed. The small particle sizes (typically 18-62 nm) with the zeta potential of -39 to -54.5 mV were obtained when mixed emulsifiers with HLB values of 12.6 and 15.1 were employed. With HLB values of 12.6 and 15.1, nanoemulsions loaded with mangostin extracts prepared with mixed VCO-PG and pure PG-based extracts showed approximately a 2 to 3-fold lower droplet size diameter when compared with the VCO-based extract. For the stability test, all nanoemulsions were stable over three freeze-thaw cycles with some changes in pH, zeta potential, and droplet size. The DPPH● scavenging activity, H2O2 scavenging activity, reducing power and antibacterial activities (E. coli and S. aureus) of the nanoemulsions were greater than their corresponding bulk extracts. Nanoemulgels produced by embedding the nanoemulsions in a hydrogel matrix was homogeneous and creamy yellow-white in appearance. The nanoemulgels had a higher mangostin release (87-92%) than their normal emulgels (74-78%). Therefore, this study presented the feasibility of nanoemulsions and nanoemulgels loaded with mangostin extracts as a promising delivery system for bioactive polyphenol in food supplements, pharmaceuticals and cosmetics.


Assuntos
Antibacterianos/química , Nanopartículas/química , Extratos Vegetais/farmacologia , Xantonas/química , Antibacterianos/farmacologia , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Óleo de Coco/química , Emulsões/química , Emulsões/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Sequestradores de Radicais Livres/química , Peróxido de Hidrogênio/química , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Picratos/química , Picratos/farmacologia , Extratos Vegetais/química , Propilenoglicol/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Xantonas/farmacologia
4.
Pharm Dev Technol ; 25(2): 168-177, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31642728

RESUMO

Fenofibrate is antihyperlipidemic which has low and variable oral bioavailability due to erratic dissolution characteristics. Niacin showed a potential atheroprotective effects suggesting possible co-administration with fenofibrate with a potential for development of fixed dose combination. The chemical structure of both drugs highlights the opportunity for interaction upon co-processing due to the existence of complementary hydrogen bonding sites. Accordingly, fenofibrate and niacin were co-processed by wet co-grinding and the resulting product was assessed using scanning electron microscopy, FTIR, thermal analysis and X-ray diffraction in addition to dissolution studies. The instrumental analysis indicated the development of submicron fenofibrate crystals stabilized over the surface of niacin crystals. The developed submicron crystals showed fast dissolution of fenofibrate depending on the relative proportions of fenofibrate to niacin. Co-processing of both drugs at dose ratio which contained higher proportion of niacin resulted in further enhancement in the dissolution rate. This further enhancement was attributed to the hydrotropic effect of niacin which was proved by solubility study in addition to size reduction. This supposition was confirmed from the inferior dissolution of fenofibrate from the physical mixture. The study introduces fenofibrate/niacin as potential fixed dose combination for augmented dissolution rate and pharmacological effects.


Assuntos
Portadores de Fármacos/química , Fenofibrato/química , Niacina/química , Administração Oral , Disponibilidade Biológica , Varredura Diferencial de Calorimetria/métodos , Química Farmacêutica/métodos , Ligação de Hidrogênio/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Hipolipemiantes/química , Microscopia Eletrônica de Varredura/métodos , Tamanho da Partícula , Solubilidade/efeitos dos fármacos , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Difração de Raios X/métodos
5.
Yeast ; 37(1): 117-129, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31826306

RESUMO

Adherence of the fungus, Candida albicans, to biotic (e.g. human tissues) and abiotic (e.g. catheters) surfaces can lead to emergence of opportunistic infections in humans. The process of adhesion and further biofilm development depends, in part, on cell surface hydrophobicity (CSH). In this study, we compared the resistance of C. albicans strains with different CSH to the most commonly prescribed antifungal drug, fluconazole, and the newly described synergistic combination, fluconazole and gentamicin. The hydrophobic strain was more resistant to fluconazole due to, among others, overexpression of the ERG11 gene encoding the fluconazole target protein (CYP51A1, Erg11p), which leads to overproduction of ergosterol in this strain. Additionally, the hydrophobic strain displayed high efflux activity of the multidrug resistance Cdr1 pump due to high expression of the CDR1 gene. On the other hand, the hydrophobic C. albicans strain was more susceptible to fluconazole-gentamicin combination because of its different effect on lipid content in the two strains. The combination resulted in ergosterol depletion with subsequent Cdr1p mislocalization and loss of activity in the hydrophobic strain. We propose that C. albicans strains with different CSH may possess altered lipid metabolism and consequently may differ in their response to treatment.


Assuntos
Antifúngicos/farmacologia , Candida albicans/química , Candida albicans/efeitos dos fármacos , Fluconazol/farmacologia , Gentamicinas/farmacologia , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Lipídeos/análise , Candida albicans/genética , Farmacorresistência Fúngica/genética , Sinergismo Farmacológico , Proteínas Fúngicas/genética , Proteínas de Membrana Transportadoras/genética , Testes de Sensibilidade Microbiana
6.
J Agric Food Chem ; 67(14): 3946-3955, 2019 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-30900456

RESUMO

Fibrillogenesis of α-synuclein (αSN) is associated with the onset and progression of Parkinson's disease (PD). Dihydromyricetin (DHM), a natural flavonoid compound extracted from Ampelopsis grossedentata, has proven antioxidative, antineuroinflammatory, and neuroprotective effects in dementia. However, it remains unclear if DHM can impede αSN fibrillogenesis and attenuate the corresponding cytotoxicity. Herein, we found that DHM could inhibit αSN fibrillogenesis and destabilize mature αSN fibrils in a dose-dependent manner. Moreover, DHM protected against αSN-induced cytotoxicity by improving the cell viability by 34.73 ± 3.68% at a 1:1 molar ratio of αSN to DHM. Molecular dynamics simulations showed that DHM interacts with the αSN trimer mainly via nonpolar mechanisms. The key residues by which αSN interacts with DHM were hydrophobic, and their side chains and main chains showed a synergistic effect via hydrophobic and hydrogen-bonding interactions. These findings suggest that DHM possesses great potential to be developed into a new aggregation inhibitor for αSN.


Assuntos
Peptídeos beta-Amiloides/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Flavonóis/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/metabolismo , alfa-Sinucleína/química , Ampelopsis/química , Peptídeos beta-Amiloides/química , Animais , Apoptose/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Flavonóis/química , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Neurônios/citologia , Neurônios/metabolismo , Fármacos Neuroprotetores/química , Células PC12 , Doença de Parkinson/genética , Agregados Proteicos/efeitos dos fármacos , Ratos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
7.
Nucleic Acids Res ; 47(4): 1637-1652, 2019 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-30649466

RESUMO

The DNA binding domain (DBD) of the tumor suppressor p53 is the site of several oncogenic mutations. A subset of these mutations lowers the unfolding temperature of the DBD. Unfolding leads to the exposure of a hydrophobic ß-strand and nucleates aggregation which results in pathologies through loss of function and dominant negative/gain of function effects. Inspired by the hypothesis that structural changes that are associated with events initiating unfolding in DBD are likely to present opportunities for inhibition, we investigate the dynamics of the wild type (WT) and some aggregating mutants through extensive all atom explicit solvent MD simulations. Simulations reveal differential conformational sampling between the WT and the mutants of a turn region (S6-S7) that is contiguous to a known aggregation-prone region (APR). The conformational properties of the S6-S7 turn appear to be modulated by a network of interacting residues. We speculate that changes that take place in this network as a result of the mutational stress result in the events that destabilize the DBD and initiate unfolding. These perturbations also result in the emergence of a novel pocket that appears to have druggable characteristics. FDA approved drugs are computationally screened against this pocket.


Assuntos
Proteínas de Ligação a DNA/química , Proteínas Mutantes/química , Bibliotecas de Moléculas Pequenas/química , Proteína Supressora de Tumor p53/química , Proteínas de Ligação a DNA/genética , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Modelos Moleculares , Simulação de Dinâmica Molecular , Proteínas Mutantes/genética , Mutação/genética , Conformação Proteica/efeitos dos fármacos , Domínios Proteicos/efeitos dos fármacos , Domínios Proteicos/genética , Desdobramento de Proteína/efeitos dos fármacos , Proteína Supressora de Tumor p53/genética
8.
Biomed Pharmacother ; 109: 2182-2191, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30551475

RESUMO

This work focused on characterizing hydrophilic fractions of Clematis flammula (CFl). The data here clearly demonstrated that hydrolate fractions act as a free radical scavengers and inhibited proliferation of different cell lines in a time- and concentration-dependent manner, transwell, and with a significant cytotoxic effect. Treating cells with CFl had the effect of suppressing cell growth attenuated by ROS generation in colonic carcinoma. Moreover, CFl in HCT116 cells suppressed survival, proliferation, invasion, angiogenesis and metastasis in vitro by inhibiting gene expression. Following CFl treatment, caspases and PARP cleavage were detected. The up- and down-regulated genes obtained from the WBA of the effect of CFl showed that several biological processes were associated with apoptosis and induction of G1 cell cycle arrest. CFl synergizes the effect of TRAIL by down-regulating the expression of cell survival proteins involved in apoptosis compared to cells treated with CFl or TRAIL alone. Our findings showed that CFl sensitizes apoptosis in TRAIL-resistant cells by activating MAPKs, SP1, and CHOP, that induced DR5 expression. Overall, our data showed that CFl is a promising antitumor agent through kinases and transcription factor induction, both of which are required to activate TRAIL receptors. Colon inflammation induced by LPS was inhibited by CFl hydrolate.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Clematis , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Extratos Vegetais/uso terapêutico , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Animais , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Neoplasias do Colo/patologia , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HL-60 , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Células MCF-7 , Camundongos , Componentes Aéreos da Planta , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia
9.
Microb Pathog ; 126: 379-392, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30476580

RESUMO

The emerging prevalence of multidrug-resistance in Gram-negative pathogens, due to conventional antimicrobial therapeutics, has led the researchers to emphasize on development of alternative novel strategies to suppress the bacterial virulence and pathogenicity through inhibition of quorum sensing (QS) and biofilms. QS is a bacterial communication system to produce density-dependent response via chemical signalling that controls pathogenesis and biofilms formation. Leaves of green tea are used worldwide as beverage which is also known for its broad-spectrum therapeutic efficacy. In this work, we have identified and characterized the most bioactive faction of green tea extract and evaluated the anti-QS and antibiofilm activity of green tea ethyl acetate fraction (GTEF) i.e. most active fraction, on three different Gram-negative bacterial pathogens. GTEF inhibited the violacein production by >75% in C. violaceum 12472. Many virulence factors of P. aeruginosa PAO1 viz. pyocyanin, pyoverdin, exoprotease, elastase, rhamnolipid production, and swimming motility were remarkably reduced in presence of sub-MICs of GTEF. Moreover, prodigiosin, protease activity, cell surface hydrophobicity, and swimming of S. marcescens MTCC 97 were also decreased significantly by the supplementation of GTEF in culture media. GTEF exhibited broad-spectrum antibiofilm action with >80% reduction in biofilm formation of test pathogens. In silico studies gave a mechanistic insight of action of GTEF. Molecular modelling revealed that phytoconstituents detected by GC/MS exhibited affinity (in order of 104 M-1) towards AHL synthases (LasI and EsaI). The molecular binding between phytocompounds and receptor proteins (LasR, RhlR, and PqsR) of QS circuit was also energetically favourable (ΔG°≥ 5.0 kcal mol-1) and supported by hydrogen bonds and hydrophobic interactions. These compounds were found to be docked in ligand binding domain of CviR and occupied same cavity as that of its antagonist. Squalene and thunbergol interacted with LasA at tartaric acid binding pocket and the complex was strengthened with binding energy -5.9 kcal mol-1. Moreover, interaction of thunbergol with biofilm-associated proteins viz. PilT and PilY1, might be disabling the pilus assembly and consequently inhibiting biofilm formation. In vivo validation of results suggested the protective role GTEF against QS-mediated pathogenicity and it might become a novel non-antibiotic QS inhibitor to control bacterial infection.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Modelos Moleculares , Extratos Vegetais/farmacologia , Percepção de Quorum/efeitos dos fármacos , Chá/química , Antibacterianos/química , Proteínas de Bactérias/metabolismo , Relação Dose-Resposta a Droga , Exopeptidases/metabolismo , Glicolipídeos/metabolismo , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Indóis/farmacologia , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Oligopeptídeos/metabolismo , Peptídeo Hidrolases/efeitos dos fármacos , Extratos Vegetais/química , Folhas de Planta/química , Prodigiosina/metabolismo , Piocianina/metabolismo , Fatores de Virulência/metabolismo
10.
J Cell Physiol ; 234(6): 8182-8191, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30317632

RESUMO

Curcumin, the bioactive pigment of turmeric which has polyphenolic-hydrophobic components, has been used for the treatment of a variety of diseases. However, due to its insignificant intestinal-liver metabolism, low stability, quick systemic elimination and its hydrophobic property with low solubility, curcumin has limited bioavailability. Exosomes are nanovesicles (30-100 nm) released from diverse cell types into extracellular and, ultimately, into bio-fluids in a tightly regulated manner. Exosomes are capable of transferring lipids, proteins, RNAs and DNAs, both with and without direct cell-to-cell contact. Curcumin-encapsulated exosomes are highly bioavailable, soluble and safe, and can reach high concentrations in the blood; they, therefore, have therapeutic potential without toxic effects and immune stimulation. Thus, curcumin-encapsulated exosomes could be superior to other synthetic nanoparticles as a carrier of curcumin. The aim of the current review is to offer an overview of the in vitro, in vivo and clinical studies pertaining to the role of curcumin-primed and curcumin-encapsulated exosomes in the treatment of cancer, oxidative stress, brain disorders, cholesterol, and endothelial dysfunction.


Assuntos
Curcumina/uso terapêutico , Portadores de Fármacos , Exossomos/química , Estresse Oxidativo/efeitos dos fármacos , Curcumina/química , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Nanopartículas/química , Nanopartículas/uso terapêutico , Solubilidade
11.
Food Chem ; 245: 439-445, 2018 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-29287393

RESUMO

The dose-dependent effects of (-)-epigallocatechin-3-gallate (EGCG; at 0, 50, 100, 200, 500, and 1000 mg/L) on the physical, chemical, and oxidative stability of porcine myofibrillar protein (MP)-soybean oil emulsion systems were investigated. The results showed EGCG at all levels effectively suppressed lipid oxidation in MP emulsion composite gels during the entire chill storage (at 4 °C for 0, 3, or 7 days). The incorporation of EGCG at higher concentrations (>100 mg/L) promoted the loss of sulfhydryls, reduction of surface hydrophobicity, and aggregation and cross-linking of MP. As a result, high concentrations of EGCG (500 and 1000 mg/L) hampered emulsification and gel formation of MP. However, EGCG at lower concentrations (50-200 mg/L) improved the oxidative stability of meat emulsions without jeopardizing the textural stability.


Assuntos
Catequina/análogos & derivados , Fenômenos Químicos , Proteínas Musculares/química , Óleo de Soja/química , Animais , Catequina/farmacologia , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Emulsões , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Carne , Oxirredução/efeitos dos fármacos , Suínos
12.
Drug Deliv ; 24(1): 1690-1702, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29098877

RESUMO

Nanoparticle-based drug delivery systems are designed to reach tumor sites based on their enhanced permeation and retention effects. However, a lack of interaction of these nanoparticles with cancer cells might lead to reduced uptake in the tumors, which might compromise the therapeutic efficacy of the system. Therefore, we developed bortezomib and IR-820-loaded hybrid-lipid mesoporous silica nanoparticles conjugated with the hydrophobic-binding peptide, cyclosporine A (CsA), and referred to them as CLMSN/BIR. Upon reaching the tumor site, CsA interacts hydrophobically with the cancer cell membranes to allow effective uptake of the nanoparticles. Nanoparticles ∼160 nm in size were prepared and the stability of IR-820 significantly improved. High cellular uptake of the nanoparticles was evident with pronounced apoptotic effects in PANC-1 and MIA PaCa-2 cells that were mediated by the chemotherapeutic effect of bortezomib and the photothermal and reactive oxygen species generation effects of IR-820. An in vivo biodistribution study indicated there was high accumulation in the tumor with an enhanced photothermal effect in PANC-1 xenograft mouse tumors. Furthermore, enhanced antitumor effects in PANC-1 xenograft tumors were observed with minimal toxicity induction in the organs of mice. Cumulatively, these results indicated the promising effects of CLMSN/BIR for effective chemo-phototherapy of pancreatic cancers.


Assuntos
Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Lipídeos/química , Nanopartículas/administração & dosagem , Nanopartículas/química , Neoplasias Pancreáticas/tratamento farmacológico , Peptídeos/química , Dióxido de Silício/química , Animais , Bortezomib/química , Bortezomib/farmacologia , Linhagem Celular Tumoral , Ciclosporina/química , Ciclosporina/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Verde de Indocianina/análogos & derivados , Verde de Indocianina/química , Verde de Indocianina/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/metabolismo , Tamanho da Partícula , Fototerapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Distribuição Tecidual/efeitos dos fármacos
13.
Food Chem ; 224: 139-143, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28159248

RESUMO

Aspergillus oryzae KB produces two ß-fructofuranosidases (F1 and F2). F1 has high transferring activity and produces fructooligosaccharides from sucrose. Mycelial growth pellets were altered by the addition of Tween 20, 40 and 80 (HLB=16.7, 15.6 and 15.0, respectively) in liquid medium cultures to form small spherical pellets. The particle size of the pellets decreased with the HLB value, which corresponds to an increase in surfactant hydrophobicity. Selective F1 production and pellet size were maximized using Tween 20. Adding polyoxyethylene oleyl ethers (POEs) with various degrees of polymerization (2, 7, 10, 20 and 50: HLB=7.7, 10.7, 14.7, 17.2 and 18.2, respectively) was investigated. A minimum mean particle size was obtained using a POE with DP=10, HLB=14.7. The POE surfactants had little effect on the selective production of F1. The formation of filamentous pellets depended on the surfactant HLB value, and F1 enzymes were produced most efficiently using Tween 20.


Assuntos
Aspergillus oryzae/enzimologia , Tensoativos/farmacologia , beta-Frutofuranosidase/biossíntese , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Oligossacarídeos/biossíntese , Oligossacarídeos/isolamento & purificação , Tamanho da Partícula , Óleos de Plantas/farmacologia , Polietilenoglicóis/farmacologia , Polissorbatos/farmacologia , beta-Frutofuranosidase/isolamento & purificação
14.
Environ Pollut ; 222: 64-72, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28069370

RESUMO

Little is known about the effects of surface coating on the interaction of engineered nanoparticles (ENPs) with plants. In this study, basil (Ocimum basilicum) was cultivated for 65 days in soil amended with unmodified, hydrophobic (coated with aluminum oxide and dimethicone), and hydrophilic (coated with aluminum oxide and glycerol) titanium dioxide nanoparticles (nano-TiO2) at 125, 250, 500, and 750 mg nano-TiO2 kg-1 soil. ICP-OES/MS, SPAD meter, and UV/Vis spectrometry were used to determine Ti and essential elements in tissues, relative chlorophyll content, carbohydrates, and antioxidant response, respectively. Compared with control, hydrophobic and hydrophilic nano-TiO2 significantly reduced seed germination by 41% and 59%, respectively, while unmodified and hydrophobic nano-TiO2 significantly decreased shoot biomass by 31% and 37%, respectively (p ≤ 0.05). Roots exposed to hydrophobic particles at 750 mg kg-1 had 87% and 40% more Ti than the pristine and hydrophilic nano-TiO2; however, no differences were found in shoots. The three types of particles affected the homeostasis of essential elements: at 500 mg kg-1, unmodified particles increased Cu (104%) and Fe (90%); hydrophilic increased Fe (90%); while hydrophobic increased Mn (339%) but reduced Ca (71%), Cu (58%), and P (40%). However, only hydrophobic particles significantly reduced root elongation by 53%. Unmodified, hydrophobic, and hydrophilic particles significantly reduced total sugar by 39%, 38%, and 66%, respectively, compared with control. Moreover, unmodified particles significantly decreased reducing sugar (34%), while hydrophobic particles significantly reduced starch (35%). Although the three particles affected basil plants, coated particles impacted the most its nutritional quality, since they altered more essential elements, starch, and reducing sugars.


Assuntos
Disponibilidade Biológica , Germinação/efeitos dos fármacos , Ocimum basilicum/efeitos dos fármacos , Ocimum basilicum/crescimento & desenvolvimento , Raízes de Plantas/efeitos dos fármacos , Brotos de Planta/efeitos dos fármacos , Titânio/química , Óxido de Alumínio/química , Biomassa , Dimetilpolisiloxanos/química , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Nanopartículas , Raízes de Plantas/crescimento & desenvolvimento , Brotos de Planta/crescimento & desenvolvimento , Solo/química , Titânio/análise
15.
J Prosthodont ; 26(6): 508-515, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26618515

RESUMO

PURPOSE: To determine the in vitro effectiveness of Plantago major extract, along with two of its active components, aucubin and baicalein, on the inhibition of Candida albicans growth, biofilm formation, metabolic activity, and cell surface hydrophobicity. MATERIALS AND METHODS: Twofold dilutions of P. major, aucubin, and baicalein were used to determine the minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and the minimum biofilm inhibitory concentration (MBIC) of each solution. Separately, twofold dilutions of P. major, aucubin, and baicalein were used to determine the metabolic activity of established C. albicans biofilm using a 2,3-bis (2- methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-carboxanilide reduction assay. Twofold dilutions of P. major, aucubin, and baicalein were used to determine the cell surface hydrophobicity of treated C. albicans biofilm by a two-phase assay using hexadecane. The hydrophobicity percentage of the cell surface was then calculated. A mixed-model ANOVA test was used for intergroup comparisons. RESULTS: The MICs of P. major extract (diluted 1:2 to 1:8), aucubin (61 to 244 µg/ml), and baicalein (0.0063 to 100 µg/ml) on the total growth of C. albicans were noticeable at their highest concentrations, and the inhibition was dose dependent. The MFC was evaluated after 48 hours of incubation, and aucubin (244 µg/ml) exhibited a strong fungicidal activity at its highest concentration against C. albicans growth. The MBIC indicated no growth or reduced growth of C. albicans biofilm at the highest concentrations of aucubin (61 to 244 µg/ml) and baicalein (25 to 100 µg/ml). Similarly, the effects of these reagents on C. albicans biofilm metabolic activity and hydrophobicity demonstrated high effectiveness at their highest concentrations. CONCLUSION: P. major extract, aucubin, and baicalein caused a dose-dependent reduction on the total growth, biofilm formation, metabolic activity, and cell surface hydrophobicity of C. albicans. This demonstrates their effectiveness as antifungals and suggests their promising potential use as solutions for C. albicans biofilm-related infections.


Assuntos
Biofilmes/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Candida albicans/fisiologia , Flavanonas/farmacologia , Glucosídeos Iridoides/farmacologia , Extratos Vegetais/farmacologia , Plantago , Candida albicans/metabolismo , Membrana Celular/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Testes de Sensibilidade Microbiana
16.
Molecules ; 21(12)2016 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-27916806

RESUMO

In the present study we investigated activity of oleuropein, a complex phenol present in large quantities in olive tree products, against opportunistic fungal pathogen Candida albicans. Oleuropein was found to have in vitro antifungal activity with a minimal inhibitory concentration (MIC) value of 12.5 mg·mL-1. Morphological changes in the nuclei after staining with fluorescent DNA-binding dyes revealed that apoptosis was a primary mode of cell death in the analyzed samples treated with subinhibitory concentrations of oleuropein. Our results suggest that this antifungal agent targets virulence factors essential for establishment of the fungal infection. We noticed that oleuropein modulates morphogenetic conversion and inhibits filamentation of C. albicans. The hydrophobicity assay showed that oleuropein in sub-MIC values has significantly decreased, in both aerobic and anaerobic conditions, the cellular surface hydrophobicity (CSH) of C. albicans, a factor associated with adhesion to epithelial cells. It was also demonstrated that the tested compound inhibits the activity of SAPs, cellular enzymes secreted by C. albicans, which are reported to be related to the pathogenicity of the fungi. Additionally, we detected that oleuropein causes a reduction in total sterol content in the membrane of C. albicans cells, which might be involved in the mechanism of its antifungal activity.


Assuntos
Antifúngicos/farmacologia , Apoptose/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Iridoides/farmacologia , Candida albicans/patogenicidade , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Glucosídeos Iridoides , Testes de Sensibilidade Microbiana , Olea/química , Preparações de Plantas/farmacologia , Fatores de Virulência
17.
Nat Commun ; 7: 12579, 2016 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-27573496

RESUMO

Protein disulfide isomerase (PDI) is an oxidoreductase essential for folding proteins in the endoplasmic reticulum. The domain structure of PDI is a-b-b'-x-a', wherein the thioredoxin-like a and a' domains mediate disulfide bond shuffling and b and b' domains are substrate binding. The b' and a' domains are connected via the x-linker, a 19-amino-acid flexible peptide. Here we identify a class of compounds, termed bepristats, that target the substrate-binding pocket of b'. Bepristats reversibly block substrate binding and inhibit platelet aggregation and thrombus formation in vivo. Ligation of the substrate-binding pocket by bepristats paradoxically enhances catalytic activity of a and a' by displacing the x-linker, which acts as an allosteric switch to augment reductase activity in the catalytic domains. This substrate-driven allosteric switch is also activated by peptides and proteins and is present in other thiol isomerases. Our results demonstrate a mechanism whereby binding of a substrate to thiol isomerases enhances catalytic activity of remote domains.


Assuntos
Retículo Endoplasmático/metabolismo , Inibidores Enzimáticos/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Isomerases de Dissulfetos de Proteínas/metabolismo , Dobramento de Proteína , Regulação Alostérica/efeitos dos fármacos , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/fisiologia , Domínio Catalítico/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/uso terapêutico , Voluntários Saudáveis , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica/efeitos dos fármacos , Isomerases de Dissulfetos de Proteínas/antagonistas & inibidores , Isomerases de Dissulfetos de Proteínas/química , Estrutura Terciária de Proteína/efeitos dos fármacos , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Trombose/sangue , Trombose/tratamento farmacológico , Trombose/patologia
18.
Ecotoxicol Environ Saf ; 131: 127-34, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27232205

RESUMO

Biotransformation of aromatic compounds is a challenge due to their low aqueous solubility and sorptive losses. The main obstacle in this process is binding of organic pollutants to the microbial cell surface. To overcome these, we applied saponins from plant extract to the microbial culture, to increase pollutants solubility and enhance diffusive massive transfer. This study investigated the efficiency of Quillaja saponaria and Sapindus mukorossi saponins-rich extracts on biodegradation of halogenated phenols by Raoultella planticola WS2 and Pseudomonas sp. OS2, as an effect of cell surface modification of tested strains. Both strains display changes in inner membrane permeability and cell surface hydrophobicity in the presence of saponins during the process of halogenated phenols biotransformation. This allows them to more efficient pollutants removal from the environment. However, only in case of the Pseudomonas sp. OS2 the addition of surfactants to the culture improved effectiveness of bromo-, chloro- and fluorophenols biodegradation. Also introduction of surfactant allowed higher biodegradability of halogenated phenols and can shorten the process. Therefore this suggests that usage of plant saponins can indicate more successful halogenated phenols biodegradation for selected strains.


Assuntos
Enterobacteriaceae/metabolismo , Fenóis/metabolismo , Extratos Vegetais/farmacologia , Pseudomonas/metabolismo , Saponinas/farmacologia , Aderência Bacteriana/efeitos dos fármacos , Biodegradação Ambiental/efeitos dos fármacos , Biotransformação/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Halogenação/efeitos dos fármacos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Extratos Vegetais/química , Eletricidade Estática , Tensoativos/farmacologia
19.
Molecules ; 21(2)2016 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-26901172

RESUMO

This review paper summarizes the antibacterial effects of phytochemicals of various medicinal plants against pathogenic and cariogenic streptococcal species. The information suggests that these phytochemicals have potential as alternatives to the classical antibiotics currently used for the treatment of streptococcal infections. The phytochemicals demonstrate direct bactericidal or bacteriostatic effects, such as: (i) prevention of bacterial adherence to mucosal surfaces of the pharynx, skin, and teeth surface; (ii) inhibition of glycolytic enzymes and pH drop; (iii) reduction of biofilm and plaque formation; and (iv) cell surface hydrophobicity. Collectively, findings from numerous studies suggest that phytochemicals could be used as drugs for elimination of infections with minimal side effects.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Streptococcus/efeitos dos fármacos , Proteínas de Bactérias/metabolismo , Cárie Dentária/microbiologia , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Faringe/microbiologia , Pele/microbiologia , Streptococcus/classificação , Streptococcus/enzimologia
20.
Lett Appl Microbiol ; 61(1): 13-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25800811

RESUMO

UNLABELLED: This study evaluated the effect of soy lecithin on the bile resistance of Lactobacillus plantarum. Six strains were cultured in MRS broth supplemented with soy lecithin at different concentrations. The strains incubated in MRS broth with 1·0% soy lecithin showed no inhibitory effect on cell growth. After culturing in MRS broth with 0·2-1·0% soy lecithin, the survival rate of harvested cells increased significantly (P < 0·05) in the 0·3% bile challenge compared with the no added soy lecithin group. The cells incubated with 0·6% soy lecithin were able to grow in an MRS broth with a higher bile salt content. The surface hydrophobicity and cell leakage in the bile challenge were assessed to reveal the physical changes caused by the addition of soy lecithin. The cell surface hydrophobicity was enhanced and the membrane integrity in the bile challenge increased after culturing with soy lecithin. A shift in the fatty acid composition was also observed, illustrating the cell membrane change in the soy lecithin culture. SIGNIFICANCE AND IMPACT OF THE STUDY: In this study, we report for the first time the beneficial effect of adding soy lecithin to an MRS broth on subsequent bile tolerance of Lactobacillus plantarum. Soy lecithin had no inhibitory effect on strain viability but significantly enhanced bile resistance. Surface hydrophobicity and cell integrity increased in strains cultured with soy lecithin. The observed shift in the cell fatty acid composition indicated changes to the cell membrane. As soy lecithin is safe for use in the food industry, its protective effects can be harnessed for the development of bile-sensitive strains with health-benefit functions for use in probiotic products.


Assuntos
Bile/microbiologia , Lactobacillus plantarum/crescimento & desenvolvimento , Lecitinas/farmacologia , Probióticos , Ácidos e Sais Biliares/química , Membrana Celular/metabolismo , Ácidos Graxos/metabolismo , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Lactobacillus plantarum/efeitos dos fármacos , Glycine max/metabolismo
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