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1.
J Agric Food Chem ; 67(49): 13706-13717, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31693347

RESUMO

Tomato storage conditions are difficult largely due to Botrytis cinerea infection which causes gray mold disease. However, the effects of the volatile organic compounds (VOCs) emitted by postharvest tomatoes on this fungus remain unclear. We analyzed the effects of tomato-emitted VOCs on B. cinerea pathogenicity, germination, and hyphal growth with bioassay, predicted the causative active compounds by principle component analysis, identified G-protein-coupled receptors (GPCRs) which captured chemical signals in the B. cinerea genome by stimulating molecular docking, tested the binding affinities of these receptors for the active compounds by fluorescence binding competition assay, and identified an associated signaling pathway by RNA interfere. The VOCs emitted by postharvest tomatoes inhibited B. cinerea; ethylene and benzaldehyde were the active compounds causing this effect. One of the identified GPCRs in B. cinerea, BcGPR3, bound tightly to both active compounds. Two genes associated with the cAMP signaling pathway (BcRcn1 and BcCnA) were downregulated in wild-type B. cinerea exposed to the active compounds, as well as in the ΔBcgpr3 B. cinerea mutant. Exposure to postharvest tomato VOCs reduces B. cinerea pathogenicity due to ethylene and benzaldehyde volatiles. The BcGPR3 protein is inactivated by the active compounds, and thus fails to transmit signals to the cAMP pathway, thereby inhibiting B. cinerea.


Assuntos
Benzaldeídos/farmacologia , Botrytis/efeitos dos fármacos , AMP Cíclico/metabolismo , Etilenos/farmacologia , Proteínas Fúngicas/metabolismo , Lycopersicon esculentum/química , Receptores Acoplados a Proteínas-G/metabolismo , Benzaldeídos/metabolismo , Botrytis/genética , Botrytis/metabolismo , Etilenos/metabolismo , Proteínas Fúngicas/genética , Lycopersicon esculentum/metabolismo , Simulação de Acoplamento Molecular , Doenças das Plantas/microbiologia , Receptores Acoplados a Proteínas-G/genética , Transdução de Sinais/efeitos dos fármacos , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/farmacologia
2.
J Microbiol Biotechnol ; 29(8): 1193-1203, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31280521

RESUMO

We investigated the protective effects of 3-bromo-4,5-dihydroxybenzaldehyde (BDB) from Polysiphonia morrowii Harvey against hydrogen peroxide (H2O2)-induced apoptosis in Vero cells. BDB exhibited scavenging activity for DPPH, hydroxyl, and alkyl radicals. BDB also inhibited H2O2-induced lipid peroxidation, cell death, and apoptosis in Vero cells by inhibiting the production of ROS. To evaluate the molecular mechanisms of apoptosis inhibition, the expression of Bax/Bcl-xL and NF-κB was assessed by western blot assay. BDB significantly suppressed the cleavage of caspase-9 and PARP and reduced Bax levels in H2O2-induced Vero cells. Besides, BDB suppressed the phosphorylation of NF-κB and the translocation of p65 in H2O2-induced cells. Furthermore, we evaluated the effect of BDB on ROS production, cell death, and lipid peroxidation in an H2O2-stimulated zebrafish embryo model. Taken together, these results indicated that ROS generation and cell death were significantly inhibited by BDB in zebrafish embryos, thereby proving that BDB exerts excellent antioxidant activity in vitro and in vivo.


Assuntos
Benzaldeídos/farmacologia , Peróxido de Hidrogênio/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rodófitas/química , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Caspase 9/metabolismo , Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Sobrevivência Celular , Feminino , Peroxidação de Lipídeos , Masculino , Modelos Animais , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Células Vero , Peixe-Zebra/anormalidades , Proteína X Associada a bcl-2/metabolismo , Proteína bcl-X/metabolismo
3.
J Food Sci ; 84(7): 1920-1928, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31264720

RESUMO

Vanillin, a kind of phenolic compound, is naturally found in food and beverage and widely used as a flavoring agent. In view of the safety and universality of vanillin, exploring the functions of vanillin on human is of great value. Thus, lipopolysaccharide (LPS)-activated THP-1 cells were selected as the cell model to evaluate the anti-inflammatory effect of vanillin in this study. On the basis of the results, vanillin markedly suppressed the expression of inflammatory cytokines (that is, TNF-α, IL-1ß, IL-6, and IL-8), mediators (NO, iNOS, PGE2, and COX-2), and NLRP3 inflammasome (that is, NLRP3, ASC, and caspase-1), blocked the LPS-induced activation of the NF-κB/IκBα/AP-1 signaling pathway, and activated the gene expression of the Nrf2/HO-1 signaling pathway. In addition, it was confirmed that vanillin was unable to react with LPS due to the results of quantification by HS-SPME-GC-MS. Hence, vanillin could effectively attenuate LPS-induced inflammatory response by regulating the expression of intracellular signaling pathways in THP-1 cells. It is a potent anti-inflammatory component found in food and beverage. These findings might contribute to the overall understanding of the potential health benefits of vanillin for food application. PRACTICAL APPLICATION: In this study, the anti-inflammatory effect of vanillin (VA) was evaluated by ELISA, real-time PCR, and western blot in LPS-induced THP-1 cells. The hypothesis that VA could react with LPS was excluded due to the results of quantification by HS-SPME-GC-MS. On the basis of the result, vanillin could effectively attenuate LPS-induced inflammatory response in THP-1 cells and was a potent anti-inflammatory component natural in food and beverage. These findings might contribute to the overall understanding of the potential health benefits of vanillin for food application.


Assuntos
Anti-Inflamatórios/farmacologia , Benzaldeídos/farmacologia , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , Ciclo-Oxigenase 2/imunologia , Humanos , Inflamassomos/efeitos dos fármacos , Inflamassomos/imunologia , Interleucina-1beta/imunologia , Lipopolissacarídeos/imunologia , Monócitos/imunologia , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Óxido Nítrico Sintase Tipo II/imunologia , Células THP-1
4.
Biol Pharm Bull ; 42(7): 1146-1154, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31257291

RESUMO

Helicid (4-formylphenyl-O-ß-D-allopyranoside), an active component found in seeds from the Chinese herb Helicia nilagirica, has been reported to exert sedative, analgesic, hypnotic and antidepressant effects. The present study was designed to evaluate the antidepressant, learning and cognitive improvement effects of helicid in a chronic unpredictable mild stress (CUMS) model of depression in rats and to explore cAMP/protein kinase A (PKA)/cAMP response element-binding (CREB) signaling pathway. Sprague-Dawley rats were randomly assigned to six groups (n = 10): control; CUMS; CUMS + fluoxetine (5 mg/kg) and CUMS + helicid at 8, 16 and 32 mg/kg. All rats were subjected to 12 weeks of CUMS protocols and drug administration during the last 6 weeks of CUMS. Our results showed that helicid, at a dose of 32 mg/kg, significantly reversed decreases in body weight and sucrose consumption, increased the distance and number of crossings in the open-field test (OFT), reduced immobility times in the forced swimming test (FST) and improved spatial memory in the Morris water maze (MWM); all of these effects had been induced by CUMS paradigm. Immunohistochemistry showed that administration of helicid could promoted the proliferation of neurons in the hippocampal CA1 and dentate gyrus (DG) regions. CUMS rats treated with helicid had dramatically decreased protein levels of serotonin transporters (SERTs). In addition, CUMS resulted in a significant reduction in the expression of cAMP, PKA C-α and p-CREB, each of which were partially attenuated by helicid administration. These results indicated that helicid could improve depressive behaviors, learning and cognitive deficits and increase hippocampal neurogenesis, which may be mediated by the regulation of SERTs, activation of the cAMP/PKA/CREB signaling pathway and upregulation of p-CREB levels in hippocampal.


Assuntos
Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Benzaldeídos/farmacologia , Benzaldeídos/uso terapêutico , Depressão/tratamento farmacológico , Estresse Psicológico/tratamento farmacológico , Animais , Cognição/efeitos dos fármacos , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Depressão/metabolismo , Depressão/psicologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiologia , Aprendizagem/efeitos dos fármacos , Masculino , Neurogênese/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia
5.
Mar Drugs ; 17(7)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288374

RESUMO

Marine organisms are recognized as a source of compounds with interesting biological activities. Vibrio neocaledonicus has been reported on for its high effectiveness against corrosion in metals but it has been little studied for its chemical and biological activities. In this study, four compounds were isolated from V. neocaledonicus: indole (1); 1H-indole-3-carboxaldehyde (2); 4-hydroxybenzaldehyde (3) and Cyclo (-Pro-Tyr) (4); using a bioassay-guided method, since in a previous study it was found that the ethyl acetate extract was active on the enzymes acetylcholinesterase (AChE), alpha-glucosidase (AG) and xanthine oxidase (XO). The inhibitory activities of the three compounds against AChE, AG and XO was also evaluated. In addition, the enzymatic inhibitory activity of indole to the toxins from the venom of Bothrops asper was tested. Results showed that indole exhibited strong inhibitory activity to AG (IC50 = 18.65 ± 1.1 µM), to AChE, and XO (51.3% and 44.3% at 50 µg/mL, respectively). 1H-indole-3-carboxaldehyde displayed strong activity to XO (IC50 = 13.36 ± 0.39 µM). 4-hydroxybenzaldehyde showed moderate activity to XO (50.75% at 50 µg/mL) and weak activity to AChE (25.7% at 50 µg/mL). Furthermore, indole showed a significant in vitro inhibition to the coagulant effect induced by 1.0 µg of venom. The findings were supported by molecular docking. This is the first comprehensive report on the chemistry of V. neocaledonicus and the bioactivity of its metabolites.


Assuntos
Organismos Aquáticos/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Enzimas/química , Vibrio/química , Benzaldeídos/química , Benzaldeídos/farmacologia , Indóis/química , Indóis/farmacologia , Simulação de Acoplamento Molecular/métodos
6.
J Pharm Pharmacol ; 71(8): 1324-1338, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31168820

RESUMO

OBJECTIVES: Cuminaldehyde self-emulsified nanoemulsion (CuA-SEN) was prepared and optimised to improve its oral bioavailability and antihepatotoxicity. METHODS: Cuminaldehyde self-emulsified nanoemulsion was developed through the self-nanoemulsification method using Box-Behnken Design (BBD) tool while appropriate physicochemical indices were evaluated. The optimised CuA-SEN was characterised via droplet size (DS), morphology, polydispersity index (PDI), zeta potential (ZP), entrapment efficiency, in-vitro release, and pharmacokinetic studies while its antihepatotoxicity was evaluated. KEY FINDINGS: Cuminaldehyde self-emulsified nanoemulsion with acceptable characteristics (mean DS-48.83 ± 1.06 nm; PDI-0.232 ± 0.140; ZP-29.92 ± 1.66 mV; EE-91.51 ± 0.44%; and drug-loading capacity (DL)-9.77 ± 0.75%) was formulated. In-vitro drug release of CuA-SEN significantly increased with an oral relative bioavailability of 171.02%. Oral administration of CuA-SEN to CCl4 -induced hepatotoxicity mice markedly increased the levels of superoxide dismutase, glutathione and catalase in serum. Also, CuA-SEN reduced the levels of tumour necrosis factor-alpha and interleukin-6 in both serum and liver tissues while aspartate aminotransferase, alanine aminotransferase and malonaldehyde levels were significantly decreased. CONCLUSIONS: These findings showed that the improved bioavailability of cuminaldehyde via SEN provided an effective approach for enhancing antioxidation, anti-inflammation and antihepatotoxicity of the drug.


Assuntos
Benzaldeídos/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Emulsões/farmacologia , Nanoestruturas/administração & dosagem , Animais , Benzaldeídos/sangue , Benzaldeídos/farmacocinética , Disponibilidade Biológica , Tetracloreto de Carbono/efeitos adversos , Catalase/sangue , /farmacocinética , Liberação Controlada de Fármacos/efeitos dos fármacos , Emulsões/farmacocinética , Glutationa/sangue , Masculino , Camundongos , Tamanho da Partícula , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/sangue
7.
Curr Top Med Chem ; 19(14): 1241-1251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31223088

RESUMO

BACKGROUND: Schistosomiasis is a neglected disease, which affects millions of people in developing countries. Its treatment relies on a single therapeutic alternative, the praziquantel. This situation may lead to drug resistance which, in turn, made urgent the need for new antischistosomal agents. Nacylhydrazones are usually explored as good antimicrobial agents, but the vanillin-related N-acylhydrazones have never been tested by their antiparasitic potential. OBJECTIVE: Herein, we report the synthesis of seven analogues, three of them unpublished, their biological investigation against Schistosoma mansoni and Target Fishing studies. METHODS: The compounds were synthesized following classical synthetical approaches. The anthelmintic potential was assessed as well as their cytotoxicity profile. Confocal laser scanning microscopy and target fishing study were performed to better understand the observed antischistosomal activity. RESULTS: Compound GPQF-407 exhibited good antischistosomal activity (47.91 µM) with suitable selectivity index (4.14). Confocal laser scanning microscopy revealed that it triggered severe tegumental destruction and tubercle disintegration. Target fishing studies pointed out some probable targets, such as the serine-threonine kinases, dihydroorotate dehydrogenases and carbonic anhydrase II. CONCLUSION: The GPQF-407 was revealed to be a promising antischistosomal agent which, besides presenting the N-acylhydrazone privileged scaffold, also could be easily synthesized on large scales from commercially available materials.


Assuntos
Benzaldeídos/farmacologia , Hidrazonas/farmacologia , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia , Animais , Benzaldeídos/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Hidrazonas/síntese química , Hidrazonas/química , Estrutura Molecular , Esquistossomicidas/síntese química , Esquistossomicidas/química , Relação Estrutura-Atividade , Células Vero
8.
Molecules ; 24(12)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216742

RESUMO

Ilicicolin H is a broad-spectrum antifungal agent targeting mitochondrial cytochrome bc1 reductase. Unfortunately, ilicicolin H shows reduced activities in vivo. Here, we report our effort on the identification of ilicicolin H biosynthetic gene cluster (BGC) by genomic sequencing a producing strain, Neonectria sp. DH2, and its heterologous production in Aspergillus nidulans. In addition, a shunt product with similar antifungal activities, ilicicolin J, was uncovered. This effort would provide a base for future combinatorial biosynthesis of ilicicolin H analogues. Bioinformatics analysis suggests that the backbone of ilicicolin H is assembled by a polyketide-nonribosomal peptide synthethase (IliA), and then offloaded with a tetramic acid moiety. Similar to tenellin biosynthesis, the tetramic acid is then converted to pyridone by a putative P450, IliC. The decalin portion is most possibly constructed by a S-adenosyl-l-methionine (SAM)-dependent Diels-Alderase (IliD).


Assuntos
Antifúngicos/farmacologia , Ascomicetos/genética , Ascomicetos/metabolismo , Benzaldeídos/farmacologia , Vias Biossintéticas/genética , Genes Fúngicos , Família Multigênica , Antifúngicos/química , Antifúngicos/metabolismo , Benzaldeídos/química , Benzaldeídos/metabolismo , Cromatografia Líquida de Alta Pressão , Regulação Fúngica da Expressão Gênica , Estrutura Molecular
9.
Eur J Pharmacol ; 855: 183-191, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31082368

RESUMO

Myocardial fibrosis is associated with cardiovascular remodeling, which is characterized by abnormal collagen architecture. However, there are not yet effective strategies targeting this abnormal pathological process. The purpose of our study is to investigate the effect of protocatechualdehyde (PCA) on myocardial fibrosis for exploring the underlying target protein and molecular mechanism. We found PCA significantly suppressed isoprenaline (ISO)-induced fibrosis and collagen deposition in myocardial tissue. Then, the direct pharmacological target of PCA was identified as collagen I using cellular thermal shift assay (CETSA) coupled with stable isotope labeling with amino acids in cell culture (SILAC) technology. Surface plasmon resonance (SPR) analysis further confirmed the specific binding of PCA with collagen I. Moreover, collagen self-assembly assay and atomic force microscope analysis confirmed that PCA directly modulated collagen conformational dynamics. LC-MS/MS analysis was applied to determine lysine residues as the binding sites of PCA on collagen I by covalently cross-linking reaction. Collectively, our study suggests that PCA controls cardiovascular remodeling by mediating diffuse interstitial myocardial fibrosis. Moreover, directly targeting collagen may be a promising strategy for the treatment of heart failure and resultant myocardial fibrosis.


Assuntos
Benzaldeídos/farmacologia , Catecóis/farmacologia , Colágeno/química , Miocárdio/patologia , Animais , Linhagem Celular , Fibrose , Insuficiência Cardíaca/patologia , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Conformação Proteica/efeitos dos fármacos
10.
Meat Sci ; 155: 27-35, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31059939

RESUMO

The objective of the present experiment was to evaluate the effects of encapsuled active principles (eugenol, thymol and vanillin blend), and clove and rosemary essential oils inclusion into the finishing diets of Nellore heifers on chemical composition, collagen content, fatty acid profile and structural traits (fibers types, type I and III collagen and sarcomere length) of longissimus muscle. Treatments had no effect (P > .05) on type of fiber, the meat chemical composition or in the muscle fatty acid profile. However, the diet with clove and rosemary essential oil and the active principle blend led to an increase in sarcomere length, higher soluble collagen content and a lower amount of type III collagen (P < .05). The mixture of both active principles and essential oils clove and cinnamon essential oil, have a potential use in animal feed, favoring a greater sarcomere length, that is directly related to the increase of the meat tenderness, without altering the meat chemical composition or fatty acid profile.


Assuntos
Ração Animal/análise , Colágeno/análise , Ácidos Graxos/análise , Óleos Voláteis/farmacologia , Carne Vermelha/análise , Animais , Benzaldeídos/farmacologia , Bovinos , Dieta/veterinária , Eugenol/farmacologia , Feminino , Fibras Musculares Esqueléticas/efeitos dos fármacos , Sarcômeros/efeitos dos fármacos , Syzygium , Timol/farmacologia
11.
Mar Drugs ; 17(4)2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31010200

RESUMO

In this study, we aimed to illustrate the potential bio-effects of 3-bromo-4,5-dihydroxybenzaldehyde (3-BDB) on the antioxidant/cytoprotective enzyme heme oxygenase-1 (HO-1) in keratinocytes. The antioxidant effects of 3-BDB were examined via reverse transcription PCR, Western blotting, HO-1 activity assay, and immunocytochemistry. Chromatin immunoprecipitation analysis was performed to test for nuclear factor erythroid 2-related factor 2 (Nrf2) binding to the antioxidant response element of the HO-1 promoter. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that the cytoprotective effects of 3-BDB were mediated by the activation of extracellular signal-regulated kinase (ERK) and protein kinase B (PKB, Akt) signaling. Moreover, 3-BDB induced the phosphorylation of ERK and Akt, while inhibitors of ERK and Akt abrogated the 3-BDB-enhanced levels of HO-1 and Nrf2. Finally, 3-BDB protected cells from H2O2- and UVB-induced oxidative damage. This 3-BDB-mediated cytoprotection was suppressed by inhibitors of HO-1, ERK, and Akt. The present results indicate that 3-BDB activated Nrf2 signaling cascades in keratinocytes, which was mediated by ERK and Akt, upregulated HO-1, and induced cytoprotective effects against oxidative stress.


Assuntos
Benzaldeídos/farmacologia , Heme Oxigenase-1/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Peróxido de Hidrogênio/farmacologia , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Queratinócitos/enzimologia , Queratinócitos/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Raios Ultravioleta
12.
Nutrients ; 11(4)2019 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-31010207

RESUMO

Microbial communities are responsible for the unique functional properties of chocolate. During microbial growth, several antimicrobial and antioxidant metabolites are produced and can influence human wellbeing. In the last decades, the use of starter cultures in cocoa fermentation has been pushed to improve nutritional value, quality, and the overall product safety. However, it must be noted that unpredictable changes in cocoa flavor have been reported between the different strains from the same species used as a starter, causing a loss of desirable notes and flavors. Thus, the importance of an accurate selection of the starter cultures based on the biogenic effect to complement and optimize chocolate quality has become a major interest for the chocolate industry. This paper aimed to review the microbial communities identified from spontaneous cocoa fermentations and focused on the yeast starter strains used in cocoa beans and their sensorial and flavor profile. The potential compounds that could have health-promoting benefits like limonene, benzaldehyde, 2-phenylethanol, 2-methylbutanal, phenylacetaldehyde, and 2-phenylethyl acetate were also evaluated as their presence remained constant after roasting. Further research is needed to highlight the future perspectives of microbial volatile compounds as biomarkers to warrant food quality and safety.


Assuntos
Anti-Infecciosos/análise , Antioxidantes/análise , Cacau/química , Chocolate/microbiologia , Fermentação , Alimento Funcional/análise , Compostos Orgânicos Voláteis/análise , Acetaldeído/análogos & derivados , Acetaldeído/análise , Acetaldeído/farmacologia , Acetatos/análise , Acetatos/farmacologia , Aldeídos/análise , Aldeídos/farmacologia , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Benzaldeídos/análise , Benzaldeídos/farmacologia , Culinária , Microbiologia de Alimentos , Humanos , Limoneno/análise , Limoneno/farmacologia , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/análise , Álcool Feniletílico/farmacologia , Paladar , Compostos Orgânicos Voláteis/farmacologia , Leveduras/crescimento & desenvolvimento , Leveduras/metabolismo
13.
Biomed Pharmacother ; 115: 108879, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31035009

RESUMO

Vanillin is widely used in food and cosmetics, among other substances, for its sweet smell. However, the neuropsychological effects of vanillin inhalation have not been elucidated. In this study, we investigated the effect of vanillin inhalation on mouse behavior. First, we investigated whether the aroma of vanillin was attractive or repulsive for mice. Thereafter, the mice inhaled vanillin for 20 min before each test in a series of behavioral tests (elevated plus maze, open field, Y-maze, tail suspension, cotton bud biting, and Porsolt forced swim tests). In these tests, the mice showed a neutral response to vanillin. Mice that inhaled vanillin had a suppressed pain response in the hot plate test. In addition, the grip strength of the forelimbs of mice that inhaled vanillin was decreased. No significant differences were found between the mice inhaling vanillin and control mice in the open field, Y-maze, tail suspension, forced swimming, and aggression tests. These results show that vanillin inhalation has anti-nociceptive effects, similar to other routes of administration. The results also show that vanillin inhalation does not cause significant behavioral effects.


Assuntos
Comportamento Animal/efeitos dos fármacos , Benzaldeídos/administração & dosagem , Benzaldeídos/farmacologia , Administração por Inalação , Agressão/efeitos dos fármacos , Animais , Ansiedade/induzido quimicamente , Depressão , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Força Muscular/efeitos dos fármacos , Odorantes
14.
Hum Exp Toxicol ; 38(7): 823-832, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30974975

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is caused by fat accumulation and is related with obesity and oxidative stress. In this study, we investigated the effect of cuminaldehyde on NAFLD in rats fed a high fat diet (HFD). Male Wistar rats were fed a HFD for 42 days to induce NAFLD. The progression of NAFLD was evaluated by histology and measuring liver enzymes (alanine transaminase and aspartate transaminase), serum and hepatic lipids (total triglycerides and total cholesterol), and oxidative stress markers (thiobarbituric acid reactive substances, glutathione, superoxide dismutase, and catalase). The HFD feeding increased the liver weight and caused NAFLD, liver steatosis, hyperlipidemia, oxidative stress, and elevated liver enzymes. Administration of cuminaldehyde ameliorated the changes in hepatic morphology and liver weight, decreased levels of liver enzymes, and inhibited lipogenesis. Our findings suggest that cuminaldehyde could improve HFD-induced NAFLD via abolishment of hepatic oxidative damage and hyperlipidemia. Cuminaldehyde might be considered as a potential aromatic compound in the treatment of NAFLD and obesity through the modulation of lipid metabolism.


Assuntos
Benzaldeídos/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Animais , Benzaldeídos/farmacologia , Colesterol/sangue , Dieta Hiperlipídica , Insulina/sangue , Leptina/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos Wistar , Triglicerídeos/sangue
15.
Molecules ; 24(6)2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30893868

RESUMO

The fungal pathogens Cochliobolus australiensis and Pyricularia grisea have recently been isolated from diseased leaves of buffelgrass (Cenchrus ciliaris) in its North American range, and their ability to produce phytotoxic metabolites that could potentially be used as natural herbicides against this invasive weed was investigated. Fourteen secondary metabolites obtained from in vitro cultures of these two pathogens were tested by leaf puncture assay on the host plant at different concentrations. Radicinin and (10S, 11S)-epi-pyriculol proved to be the most promising compounds. Thus, their phytotoxic activity was also evaluated on non-host indigenous plants. Radicinin demonstrated high target-specific toxicity on buffelgrass, low toxicity to native plants, and no teratogenic, sub-lethal, or lethal effects on zebrafish (Brachydanio rerio) embryos. It is now under consideration for the development of a target-specific bioherbicide to be used against buffelgrass in natural systems where synthetic herbicides cause excessive damage to native plants.


Assuntos
Cenchrus/efeitos dos fármacos , Herbicidas/imunologia , Herbicidas/farmacologia , Pironas/farmacologia , Animais , Benzaldeídos/farmacologia , Embrião não Mamífero/efeitos dos fármacos , Álcoois Graxos/farmacologia , Peixe-Zebra
16.
FEMS Yeast Res ; 19(3)2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30834929

RESUMO

Phenolic inhibitors in lignocellulosic hydrolysates interfere with the performance of fermenting microorganisms. Among these, coniferyl aldehyde is one of the most toxic inhibitors. In this study, genetically stable Saccharomyces cerevisiae mutants with high coniferyl aldehyde resistance were successfully obtained for the first time by using an evolutionary engineering strategy, based on the systematic application of increasing coniferyl aldehyde stress in batch cultures. Among the selected coniferyl aldehyde-resistant mutants, the highly resistant strain called BH13 was also cross-resistant to other phenolic inhibitors, vanillin, ferulic acid and 4-hydroxybenzaldehyde. In the presence of 1.2 mM coniferyl aldehyde stress, BH13 had a significantly reduced lag phase, which was less than 3 h and only about 25% of that of the reference strain and converted coniferyl aldehyde faster. Additionally, there was no reduction in its growth rate, either. Comparative transcriptomic analysis of a highly coniferyl aldehyde-resistant mutant revealed upregulation of the genes involved in energy pathways, response to oxidative stress and oxidoreductase activity in the mutant strain BH13, already under non-stress conditions. Transcripts associated with pleiotropic drug resistance were also identified as upregulated. Genome re-sequencing data generally supported transcriptomic results and identified gene targets that may have a potential role in coniferyl aldehyde resistance.


Assuntos
Acroleína/análogos & derivados , Evolução Molecular Direcionada , Farmacorresistência Fúngica/genética , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Acroleína/farmacologia , Técnicas de Cultura Celular por Lotes , Benzaldeídos/farmacologia , Ácidos Cumáricos/farmacologia , Perfilação da Expressão Gênica , Genômica , Estresse Fisiológico
17.
Artigo em Inglês | MEDLINE | ID: mdl-30843483

RESUMO

AIM AND OBJECTIVE: Human full-length cyclic nucleotide phosphodiesterase isozyme 4B2 (hPDE4B2) as the target for screening and characterizing inhibitors suffers from low activity yield and the coexistence of two conformational states bearing different affinities for (R)-rolipram. Hence, the 152~528 truncate of hPDE4B2 existing only in the low-affinity conformation state for (R)-rolipram was compared against the full-length hPDE4B2 to characterize inhibitors. MATERIALS AND METHODS: With 6His-SUMO tag at the N-terminus, both the full-length hPDE 4B2 (SF-hPDE4B2) and the 152~528 truncate (ST-hPDE4B2) were expressed in Escherichia coli cells, purified through Ni-NTA column and compared for the characterization of inhibitors. The inhibition constants (Ki) of some synthesized rolipram analogues against both targets were determined with 96-well microplate through the coupled action of monophosphatase on AMP and spectrophotometric assay of phosphate with malachite green. RESULTS: After affinity purification with Ni2+-NTA column, ST-hPDE4B2 showed about 30-fold higher specific activity and 100-fold higher activity yield than SF-hPDE4B2; Ki of (R)-rolipram on ST-hPDE4B2 was consistent with that on the low-affinity state of the untagged full-length hPDE4B2 expressed in insect cells. Of some representative rolipram analogues as inhibitors, a dual-logarithm model quantitatively described their monotonic association, and Ki from 0.010 mM to 8.5 mM against SF-hPDE4B2 was predicted from Ki against ST-hPDE4B2, supporting the discovery of consistent hits by the use of both targets with a pair of properly-set cutoffs. CONCLUSION: ST-hPDE4B2 with much higher activity yield may be a favorable alternative target to characterize/screen rolipram analogues as hPDE4B inhibitors in high-throughput mode.


Assuntos
Benzaldeídos/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Inibidores Enzimáticos/farmacologia , Benzaldeídos/síntese química , Benzaldeídos/química , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Ensaios de Triagem em Larga Escala , Humanos , Isoenzimas/antagonistas & inibidores , Isoenzimas/metabolismo , Estrutura Molecular
18.
Eur J Pharmacol ; 849: 43-49, 2019 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-30707959

RESUMO

Colorectal cancer (CRC) is a common malignancy and the leading cause of cancer death worldwide. According to previous studies, vanillin possesses pharmacological and anticancer activities. In this work, we have modified the structure of vanillin to obtain a vanillin derivative called 4-(1H-imidazo [4,5-f][1,10]-phenanthrolin-2-yl)-2-methoxyphenol (IPM711), which has improved anticancer activity. The present study is intended to explore the anti-colorectal cancer activity of IPM711 in HT29 and HCT116 cells. The results of this study suggest that IPM711 can inhibit the growth, invasion and migration of HT29 and HCT116 cells. Western blot and molecular docking showed that IPM711 could bind to a Wnt/ß-catenin signaling receptor to inhibit cell growth, invasion and migration in HT29 cells. Based on these results, IPM711 is a promising anticancer drug candidate for human colorectal cancer therapy.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Benzaldeídos/química , Benzaldeídos/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos , Antineoplásicos/metabolismo , Benzaldeídos/metabolismo , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Receptores Frizzled/química , Receptores Frizzled/metabolismo , Células HCT116 , Células HT29 , Humanos , Simulação de Acoplamento Molecular , Conformação Proteica
19.
Restor Neurol Neurosci ; 37(1): 21-29, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30741707

RESUMO

BACKGROUND: In the search for treating neurological dysfunctions after spinal cord injury (SCI), methods of neuroprotection are of interest to intervene with the caspase pathway. OBJECTIVE: To evaluate the neuroprotective effects of vanillin in a rat model of spinal cord injury (SCI). METHODS: Rats were randomly assigned to one of three groups: a sham-operated group, and two groups where SCI was produced by ischemia/reperfusion which received either saline or vanillin (286 mg/kg, intraperitoneal [i.p.] 30 min prior to surgery). Neurological function was estimated by the Tarlov scale at 1, 12, and 24 h after surgery. Additionally, we estimated the levels of oxidative stress, inflammatory cytokines, and mitochondrial proteins in the homogenates of spinal tissues and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) and immunohistochemical assays of spinal tissues. RESULTS: Motor dysfunction was found to be significantly improved in the vanillin treated group compared to SCI rats. This was accompanied by altered levels of oxidative stress, inflammatory cytokines, and expressions of mitochondrial proteins in the SCI rats which were ameliorated by the vanillin treatment. Vanillin also significantly reduced the number of TUNEL-positive cells in spinal cord tissues compared to the sham group (p <  0.01) and decreased the number of hypoxia-inducible factor (HIF)-1α-positive cells. CONCLUSIONS: In the SCI rat model vanillin exerted neuroprotective effects of reducing apoptosis and attenuating the expression of HIF-1α in spinal tissues.


Assuntos
Apoptose/efeitos dos fármacos , Benzaldeídos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Apoptose/fisiologia , Modelos Animais de Doenças , Expressão Gênica/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/patologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/metabolismo , Neurônios/patologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição Aleatória , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia
20.
Am J Hematol ; 94(5): 575-584, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30784099

RESUMO

In sickle cell disease (SCD), sickle hemoglobin (HbS) polymerizes upon deoxygenation, resulting in sickling of red blood cells (RBCs). These sickled RBCs have strongly reduced deformability, leading to vaso-occlusive crises and chronic hemolytic anemia. To date, there are no reliable laboratory parameters or assays capable of predicting disease severity or monitoring treatment effects. We here report on the oxygenscan, a newly developed method to measure RBC deformability (expressed as Elongation Index - EI) as a function of pO2 . Upon a standardized, 22 minute, automated cycle of deoxygenation (pO2 median 16 mmHg ± 0.17) and reoxygenation, a number of clinically relevant parameters are produced in a highly reproducible manner (coefficients of variation <5%). In particular, physiological modulators of oxygen affinity, such as, pH and 2,3-diphosphoglycerate showed a significant correlation (respectively R = -0.993 and R = 0.980) with Point of Sickling (PoS5% ), which is defined as the pO2 where a 5% decrease in EI is observed during deoxygenation. Furthermore, in vitro treatment with antisickling agents, including GBT440, which alter the oxygen affinity of hemoglobin, caused a reproducible left-shift of the PoS, indicating improved deformability at lower oxygen tensions. When RBCs from 21 SCD patients were analyzed, we observed a significantly higher PoS in untreated homozygous SCD patients compared to treated patients and other genotypes. We conclude that the oxygenscan is a state-of-the-art technique that allows for rapid analysis of sickling behavior in SCD patients. The method is promising for personalized treatment, development of new treatment strategies and could have potential in prediction of complications.


Assuntos
Anemia Falciforme/sangue , Benzaldeídos/farmacologia , Eritrócitos Anormais/metabolismo , Hemoglobina Falciforme/metabolismo , Oxigênio/metabolismo , Pirazinas/farmacologia , Pirazóis/farmacologia , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/patologia , Eritrócitos Anormais/patologia , Humanos
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