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1.
Food Funct ; 12(19): 8920-8931, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34606549

RESUMO

The effect of adding the chokeberry fruit additive to rape honey was studied with regard to the physicochemical properties and biological activity. Two samples of dried powdered fruits were used to enrich the honey (1 and 4% v/v) during creaming. The obtained products were characterized in terms of sugar content, acidity, conductivity, total phenolic, flavonoid and anthocyanin contents and HPTLC polyphenol profiles. The antioxidant properties of enriched honeys were studied in vitro (FRAP, DPPH, and ABTS) and in vivo using a S. cerevisiae model. The inhibitory effect against 5 bacterial strains and coronavirus surrogate bacteriophage phi6 was tested. The addition of chokeberry significantly modified the physicochemical properties of honey and enhanced its antioxidant potential (from 3 to 15 times). Using HPTLC analysis, the occurrence of flavonoids, phenolic acids, and anthocyanins in chokeberry enriched honey was determined. The modified honey protected yeast cells against H2O2-induced oxidative stress when used as a pretreatment agent. All tested bacteria were susceptible to enriched honey in a dose-dependent manner. The antiviral potential of enriched honey against the model bacteriophage was discovered for the first time. In terms of numerous health benefits determined, honey enriched with Aronia melanocarpa fruits can be considered as an interesting novel functional food, which may increase the consumption of chokeberry superfruits.


Assuntos
Frutas , Alimento Funcional , Mel , Photinia , Extratos Vegetais/química , Antibacterianos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Bifenilo/química , Humanos , Picratos/química , Extratos Vegetais/farmacologia , Saccharomyces cerevisiae/efeitos dos fármacos
2.
J Biomed Nanotechnol ; 17(8): 1564-1573, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544534

RESUMO

Honokiol-loaded nanoparticles (HK-loaded NPs) exhibit potential antitumor activity; however, the factors affecting their antitumor efficacy are still unclear and need to be explored. This research was aimed to systematically estimate the influence of feed weight ratio (FWR) and nanocarrier structure on antitumor activity. Accordingly, three types of ethylene glycol derivatives, including linear poly(ethylene glycol) with molar mass of 2000 (PEG45), first and second generation oligo(ethylene glycol) dendrons (G1 and G2) were used as nanocarriers, and a series of HK-loaded NPs with different FWR were prepared successfully using the evaporation-ultrasonication method. These NPs showed similar stability but demonstrated differences with respect to particle size, morphology, cumulative profile, and antitumor efficacy. The influence of the FWR was studied using G1 dendrons as nanocarriers; the results indicated that the particle size and morphology of G1 NPs were significantly affected, and G1 NPs (8/1), with the FWR of 8/1 for HK versus G1 dendron, exhibited the highest antitumor activity among all G1 NPs. Furthermore, the influence of nanocarrier structure was investigated at the FWR of 4/1; the findings revealed reduction in the particle diameter from 280 nm to 109 nm and change in morphology from sphere to flower-like structure with an increase in the branch degree from linear to dendron. Moreover, G2 NPs (4/1), with the FWR of 4/1 for HK versus G2 dendron, carrying the highest branch degree exhibited the greatest antitumor efficacy among all. These results are suggestive of influence of particle size and morphology on antitumor efficacy of HK-loaded NPs. Conclusively, this study demonstrated nanocarrier structure and the FWR significantly affect the antitumor efficacy of NPs, which should be optimized for designing nanoscale delivery systems.


Assuntos
Portadores de Fármacos , Nanopartículas , Compostos de Bifenilo , Linhagem Celular Tumoral , Etilenoglicóis , Lignanas , Nanomedicina , Tamanho da Partícula , Poliésteres , Polietilenoglicóis
3.
Curr Microbiol ; 78(11): 3957-3967, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34550434

RESUMO

Candida albicans is the most common human fungal pathogen that has developed extensive virulence factors which allows successful colonization and infection of the host. Anti-virulence agents can alleviate the pathogenesis of fungi and help the immune system to eradicate them easily. This study aimed to explore the anti-virulence effect of domperidone and candesartan against C. albicans standard strain. Sub-inhibitory concentrations (1/4 and 1/8 of minimum inhibitory concentration) of domperidone and candesartan significantly inhibited the virulence factors hemolysin, lipase, protease, phospholipase, and bioflim formation. It was found that candesartan inhibited biofilm formation by 60.48-67.91%, hemolysin activity (61.21-74.14%), phospholipase activity (40-49.67%), lipase activity (58.97-73%), and protease activity (52.63%), while domperidone was found to inhibit biofilm formation by 70.54-77.49%, hemolysin activity (64.84-69.84%), phospholipase activity (49.67-60%), lipase activity (50-54.87%), and protease activity (52.63-57.9%). Quantitative real time-PCR confirmed the anti-virulence activity of domperidone and candesartan as both drugs significantly reduce the expression of the virulence genes SAP2, SAP6, PLB1, PLB2, LIP4, LIP5. In conclusion, domperidone and candesartan could serve as anti-virulence agents for treatment of C. albicans infections.


Assuntos
Candida albicans , Domperidona , Benzimidazóis , Compostos de Bifenilo , Domperidona/farmacologia , Humanos , Tetrazóis/farmacologia , Virulência
4.
Clin Drug Investig ; 41(10): 907-915, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34533783

RESUMO

BACKGROUND: Sacubitril-valsartan is effective in reducing the N-terminal pro-B-type natriuretic peptide level of hospitalized patients with acute decompensated heart failure, with a high acquisition cost compared with enalapril treatment. OBJECTIVE: This study aimed to determine the cost utility of sacubitril-valsartan compared with enalapril for acute decompensated heart failure treatment. METHODS: A Markov model was constructed to project the total costs, life-years, quality-adjusted life-years (QALYs) of early initiation, and a 2-month delay of sacubitril-valsartan treatment and enalapril treatment in hospitalized patients with acute decompensated heart failure over a lifetime horizon from a Thai healthcare system perspective. Clinical inputs were mainly derived from the PIONEER-HF and PARADIGM-HF trials, together with Thai epidemiological data. Cost data were based on the Thai population. All costs and outcomes were discounted at 3% annually. A series of sensitivity analyses were performed. RESULTS: Compared with enalapril, sacubitril-valsartan incurred a higher total cost per year (THB 42,994 [US$1367.48] vs THB 19,787 [US$629.37]), and it gained more QALYs (4.969 vs 4.755). The incremental cost-effectiveness ratio was THB 108,508/QALY (US$3451.26/QALY). Early initiation of sacubitril-valsartan treatment was more cost effective than delayed treatment. Sensitivity analyses revealed that at a level of willingness to pay of THB 160,000/QALY (US$5089/QALY), sacubitril-valsartan was a cost-effective strategy of about 60%. CONCLUSIONS: Sacubitril-valsartan is cost effective in patients with acute decompensated heart failure. However, the results are highly dependent on the long-term cardiovascular mortality, and they are applicable only to Thailand or countries with a similarly structured healthcare system. Long-term registries should be pursued to decrease the uncertainty around long-term mortality.


Assuntos
Enalapril , Insuficiência Cardíaca , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo , Análise Custo-Benefício , Combinação de Medicamentos , Enalapril/uso terapêutico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Hospitalização , Humanos , Volume Sistólico , Tetrazóis/uso terapêutico , Tailândia , Valsartana
5.
Ann Palliat Med ; 10(8): 8684-8691, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34488357

RESUMO

BACKGROUND: The aim of this study was to observe the effect of Sacubitril/Valsartan on cardiac function and remodeling in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: A total of 120 patients with HFrEF were selected and given standard heart failure treatment according to the 2017 ACC/AHA/HFSA guidelines. Regardless of whether patients had taken Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers (ACEI/ARB) medications previously, after admission they were treated with the minimum effective dose of Sacubitril/Valsartan according to their blood pressure reading. Baseline clinical data were recorded and patients were followed up at 1, 3, 6, 9, and 12 months post discharge, during which time the dose of Sacubitril/Valsartan was gradually increased to the maximum tolerated dose (dose range 25-200 mg/twice daily). During follow-up, N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), and left atrium diameter (LAD) were monitored; a 6-minute walking test and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores were recorded; and adverse reactions were collected. RESULTS: Over the course of the 12-month follow-up, the plasma concentrations of NT-proBNP were significantly reduced compared with the baseline, and the longer the follow-up time, the lower the NT-proBNP levels were (P<0.05). Similarly, LVEDD, LVESD and LAD were significantly smaller at 12 months than at baseline, and the longer the follow-up time, the smaller the internal diameter was (P<0.05). The LVEF, 6-minute walking distance and KCCQ scores increased significantly from baseline (P<0.05), whereas eGFR and serum potassium levels showed no significant change compared with the baseline. CONCLUSIONS: Sacubitril/Valsartan demonstrated a remarkable ability to improve cardiac function and to control cardiac remodeling with a high degree of safety in patients with HFrEF.


Assuntos
Insuficiência Cardíaca , Assistência ao Convalescente , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Alta do Paciente , Volume Sistólico , Resultado do Tratamento , Valsartana , Função Ventricular Esquerda , Remodelação Ventricular
6.
Intern Med ; 60(17): 2807-2809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34470986

RESUMO

Sacubitril/valsartan has demonstrated its prognostic advantageousness over enalapril in patients with heart failure with a reduced ejection fraction. However, the optimal therapeutic strategy using sacubitril/valsartan in real-world practice, particularly among a Japanee cohort, remains uncertain. A 75-year-old man with systolic heart failure and chronic kidney disease was administered sacubitril/valsartan. Plasma B-type natriuretic peptide transiently increased, accompanied by an increase in the urine volume, which allowed us to terminate loop diuretics. The estimated glomerular filtration rate as well as heart failure symptom improved at the one-month follow-up. Sacubitril/valsartan might be a promising option to preserve the renal function and improve clinical outcomes when the dose of concomitant diuretics can be decreased, although further large-scale studies are warranted to validate our hypothesis.


Assuntos
Insuficiência Cardíaca Sistólica , Insuficiência Cardíaca , Insuficiência Renal Crônica , Idoso , Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Compostos de Bifenilo , Combinação de Medicamentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Humanos , Japão , Masculino , Neprilisina , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Volume Sistólico , Tetrazóis/uso terapêutico , Resultado do Tratamento , Valsartana/uso terapêutico
7.
Nat Commun ; 12(1): 5426, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34521824

RESUMO

Much hope in drug development comes from the discovery of positive allosteric modulators (PAM) that display target subtype selectivity and act by increasing agonist potency and efficacy. How such compounds can allosterically influence agonist action remains unclear. Metabotropic glutamate receptors (mGlu) are G protein-coupled receptors that represent promising targets for brain diseases, and for which PAMs acting in the transmembrane domain have been developed. Here, we explore the effect of a PAM on the structural dynamics of mGlu2 in optimized detergent micelles using single molecule FRET at submillisecond timescales. We show that glutamate only partially stabilizes the extracellular domains in the active state. Full activation is only observed in the presence of a PAM or the Gi protein. Our results provide important insights on the role of allosteric modulators in mGlu activation, by stabilizing the active state of a receptor that is otherwise rapidly oscillating between active and inactive states.


Assuntos
Ácido Glutâmico/farmacologia , Receptores de Glutamato Metabotrópico/agonistas , Receptores de Glutamato Metabotrópico/química , Regulação Alostérica/efeitos dos fármacos , Sítio Alostérico , Aminoácidos/química , Aminoácidos/farmacologia , Compostos de Bifenilo/química , Compostos de Bifenilo/farmacologia , Compostos Bicíclicos com Pontes/química , Compostos Bicíclicos com Pontes/farmacologia , Compostos Bicíclicos Heterocíclicos com Pontes/química , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Domínio Catalítico , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Ésteres do Colesterol/química , Ésteres do Colesterol/farmacologia , Diosgenina/análogos & derivados , Diosgenina/química , Diosgenina/farmacologia , Dissacarídeos/química , Dissacarídeos/farmacologia , Transferência Ressonante de Energia de Fluorescência , Expressão Gênica , Glucosídeos/química , Glucosídeos/farmacologia , Glicolipídeos/química , Glicolipídeos/farmacologia , Células HEK293 , Humanos , Indanos/química , Indanos/farmacologia , Micelas , Octoxinol/química , Octoxinol/farmacologia , Ligação Proteica , Conformação Proteica , Multimerização Proteica , Receptores de Glutamato Metabotrópico/genética , Receptores de Glutamato Metabotrópico/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Imagem Individual de Molécula , Xantenos/química , Xantenos/farmacologia
8.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361759

RESUMO

Croton ferrugineus Kunth is an endemic species of Ecuador used in traditional medicine both for wound healing and as an antiseptic. In this study, fresh Croton ferrugineus leaves were collected and subjected to hydrodistillation for extraction of the essential oil. The chemical composition of the essential oil was determined by gas chromatography equipped with a flame ionization detector and gas chromatography coupled to a mass spectrometer using a non-polar and a polar chromatographic column. The antibacterial activity was assayed against three Gram-positive bacteria, one Gram-negative bacterium and one dermatophyte fungus. The radical scavenging properties of the essential oil was evaluated by means of DPPH and ABTS assays. The chemical analysis allowed us to identify thirty-five compounds representing more than 99.95% of the total composition. Aliphatic sesquiterpene hydrocarbon trans-caryophyllene was the main constituent with 20.47 ± 1.25%. Other main compounds were myrcene (11.47 ± 1.56%), ß-phellandrene (10.55 ± 0.02%), germacrene D (7.60 ± 0.60%), and α-humulene (5.49 ± 0.38%). The essential oil from Croton ferrugineus presented moderate activity against Candida albicans (ATCC 10231) with an MIC of 1000 µg/mL, a scavenging capacity SC50 of 901 ± 20 µg/mL with the ABTS method, and very strong antiglucosidase activity with an IC50 of 146 ± 20 µg/mL.


Assuntos
Anti-Infecciosos/química , Antioxidantes/química , Croton/química , Inibidores Enzimáticos/química , Óleos Voláteis/química , Folhas de Planta/química , Monoterpenos Acíclicos/química , Monoterpenos Acíclicos/isolamento & purificação , Alcenos/química , Alcenos/isolamento & purificação , Anti-Infecciosos/isolamento & purificação , Anti-Infecciosos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Monoterpenos Cicloexânicos/química , Monoterpenos Cicloexânicos/isolamento & purificação , Inibidores Enzimáticos/isolamento & purificação , Inibidores Enzimáticos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Sesquiterpenos Monocíclicos/química , Sesquiterpenos Monocíclicos/isolamento & purificação , Picratos/antagonistas & inibidores , Sesquiterpenos Policíclicos/química , Sesquiterpenos Policíclicos/isolamento & purificação , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Ácidos Sulfônicos/antagonistas & inibidores , alfa-Glucosidases/química
9.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361766

RESUMO

Hedyosmum racemosum (Ruiz & Pav.) G. is a native species of Ecuador used in traditional medicine for treatment of rheumatism, bronchitis, cold, cough, asthma, bone pain, and stomach pain. In this study, fresh H. racemosum leaves of male and female specimens were collected and subjected to hydrodistillation for the extraction of the essential oil. The chemical composition of male and female essential oil was determined by gas chromatography-gas chromatography equipped with a flame ionization detector and coupled to a mass spectrometer using a non-polar and a polar chromatographic column. The antibacterial activity was assayed against five Gram-positive and two Gram-negative bacteria, and two dermatophytes fungi. The scavenging radical properties of the essential oil were evaluated by DPPH and ABTS assays. The chemical analysis allowed us to identify forty-three compounds that represent more than 98% of the total composition. In the non-polar and polar column, α-phellandrene was the principal constituent in male (28.24 and 25.90%) and female (26.47 and 23.90%) essential oil. Other main compounds were methyl chavicol, germacrene D, methyl eugenol, and α-pinene. Female essential oil presented a strong activity against Klebsiella pneumoniae (ATCC 9997) with an minimum inhibitory concentration (MIC) of 500 µg/mL and a scavenging capacity SC50 of 800 µg/mL.


Assuntos
Antibacterianos/química , Antioxidantes/química , Monoterpenos Cicloexânicos/química , Magnoliopsida/química , Óleos Voláteis/química , Derivados de Alilbenzenos/química , Derivados de Alilbenzenos/isolamento & purificação , Anisóis/química , Anisóis/isolamento & purificação , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Arthrodermataceae/efeitos dos fármacos , Arthrodermataceae/crescimento & desenvolvimento , Benzotiazóis/antagonistas & inibidores , Monoterpenos Bicíclicos/química , Monoterpenos Bicíclicos/isolamento & purificação , Compostos de Bifenilo/antagonistas & inibidores , Monoterpenos Cicloexânicos/isolamento & purificação , Equador , Eugenol/análogos & derivados , Eugenol/química , Eugenol/isolamento & purificação , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Humanos , Magnoliopsida/metabolismo , Masculino , Testes de Sensibilidade Microbiana , Picratos/antagonistas & inibidores , Folhas de Planta/química , Plantas Medicinais , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Fatores Sexuais , Ácidos Sulfônicos/antagonistas & inibidores
10.
Int J Mol Sci ; 22(16)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34445301

RESUMO

Angiotensin receptor neprilysin inhibitor (ARNI) treatment reduces functional mitral regurgitation (MR) to a greater extent than angiotensin receptor blocker (ARB) treatment alone, but the mechanism is unclear. We evaluated the mechanisms of how ARNI has an effect on functional MR. After inducing functional MR by left circumflex coronary artery occlusion, male Sprague Dawley rats (n = 31) were randomly assigned to receive the ARNI LCZ696, the ARB valsartan, or corn oil only (MR control). Excised mitral leaflets and left ventricle (LV) were analyzed, and valvular endothelial cells were evaluated focusing on molecular changes. LCZ696 significantly attenuated LV dilatation after 6 weeks when compared with the control group (LV end-diastolic volume, 461.3 ± 13.8 µL versus 525.1 ± 23.6 µL; p < 0.05), while valsartan did not (471.2 ± 8.9 µL; p > 0.05 to control). Histopathological analysis of mitral leaflets showed that LCZ696 strongly reduced fibrotic thickness compared to the control group (28.2 ± 2.7 µm vs. 48.8 ± 7.5 µm; p < 0.05). Transforming growth factor-ß and downstream phosphorylated extracellular-signal regulated kinase were also significantly lower in the LCZ696 group. Consequently, excessive endothelial-to-mesenchymal transition (EndoMT) was mitigated in the LCZ696 group compared to the control group and leaflet area was higher (11%) in the LCZ696 group than in the valsartan group. Finally, the MR extent was significantly lower in the LCZ696 group and functional improvement was observed. In conclusion, neprilysin inhibitor has positive effects on LV reverse remodeling and also attenuates fibrosis in MV leaflets and restores adaptive growth by directly modulating EndoMT.


Assuntos
Aminobutiratos/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Insuficiência da Valva Mitral/tratamento farmacológico , Infarto do Miocárdio/tratamento farmacológico , Valsartana/uso terapêutico , Aminobutiratos/farmacologia , Antagonistas de Receptores de Angiotensina/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Animais , Compostos de Bifenilo/farmacologia , Células Cultivadas , Combinação de Medicamentos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Valva Mitral/efeitos dos fármacos , Valva Mitral/patologia , Valva Mitral/fisiologia , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/etiologia , Insuficiência da Valva Mitral/fisiopatologia , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/fisiopatologia , Traumatismo por Reperfusão Miocárdica/complicações , Traumatismo por Reperfusão Miocárdica/diagnóstico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Neprilisina/antagonistas & inibidores , Ratos , Ratos Sprague-Dawley , Valsartana/farmacologia , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos
11.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361702

RESUMO

Neurodegenerative diseases have a complex nature which highlights the need for multitarget ligands to address the complementary pathways involved in these diseases. Over the last decade, many innovative curcumin-based compounds have been designed and synthesized, searching for new derivatives having anti-amyloidogenic, inhibitory of tau formation, as well as anti-neuroinflammation, antioxidative, and AChE inhibitory activities. Regarding our experience studying 3-substituted coumarins with interesting properties for neurodegenerative diseases, our aim was to synthesize a new series of curcumin-coumarin hybrid analogues and evaluate their activity. Most of the 3-(7-phenyl-3,5-dioxohepta-1,6-dien-1-yl)coumarin derivatives 11-18 resulted in moderated inhibitors of hMAO isoforms and AChE and BuChE activity. Some of them are also capable of scavenger the free radical DPPH. Furthermore, compounds 14 and 16 showed neuroprotective activity against H2O2 in SH-SY5Y cell line. Nanoparticles formulation of these derivatives improved this property increasing the neuroprotective activity to the nanomolar range. Results suggest that by modulating the substitution pattern on both coumarin moiety and phenyl ring, ChE and MAO-targeted derivatives or derivatives with activity in cell-based phenotypic assays can be obtained.


Assuntos
Antioxidantes/síntese química , Inibidores da Colinesterase/síntese química , Cumarínicos/síntese química , Curcumina/análogos & derivados , Inibidores da Monoaminoxidase/síntese química , Fármacos Neuroprotetores/síntese química , Acetilcolinesterase/metabolismo , Animais , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Butirilcolinesterase/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Inibidores da Colinesterase/farmacologia , Cumarínicos/farmacologia , Curcumina/farmacologia , Proteínas Ligadas por GPI/metabolismo , Humanos , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Monoaminoxidase/metabolismo , Inibidores da Monoaminoxidase/farmacologia , Córtex Motor/citologia , Córtex Motor/enzimologia , Nanopartículas/química , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Fármacos Neuroprotetores/farmacologia , Picratos/antagonistas & inibidores , Cultura Primária de Células , Ratos , Relação Estrutura-Atividade
12.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361727

RESUMO

Enzymatic pretreatment of seeds is a novel approach that enhances the health benefits of the extracted oil. The study investigated the influence of the enzymatic pretreatment of seeds on the quality of oil from different pomegranate cultivars. The quality of the ultrasound-assisted (and ethanol-extracted) oil was studied, with respect to the refractive index (RI), yellowness index (YI), conjugated dienes (K232), peroxide value (PV) ρ-anisidine value (AV), total oxidation value (TOTOX), total carotenoid content (TCC), total phenolic compounds (TPC), fatty acid composition, phytosterol composition, ferric reducing antioxidant power (FRAP), and 2.2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging capacity. The seeds of three different pomegranate cultivars ('Wonderful', 'Herskawitz', and 'Acco') were digested with an equal mixture of Pectinex Ultra SPL, Flavourzyme 100 L, and cellulase crude enzymes, at a concentration, pH, temperature, and time of 1.7%, 4.5, 40 °C, and 5 h, respectively. Enzymatic pretreatment of PS increased oil yield, PV, TPC, TCC, and DPPH radical scavenging capacity, but decreased the YI. The levels of K232, AV and TOTOX, fatty acids, phytosterols, RI, and FRAP, were not significantly affected by enzymatic pretreatment of PS. Principal component analysis (PCA) established that oil extracted from the 'Acco' seed after enzymatic pretreatment had higher yield, TPC, TCC, and DPPH radical scavenging capacity. Therefore, enzyme-pretreated 'Acco' pomegranate fruit seed is a source of quality seed oil with excellent antioxidant properties.


Assuntos
Antioxidantes/isolamento & purificação , Hidrolases/química , Extração Líquido-Líquido/métodos , Óleos Vegetais/isolamento & purificação , Romã (Fruta)/química , Sementes/química , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Carotenoides/química , Carotenoides/isolamento & purificação , Carotenoides/farmacologia , Etanol/química , Ácidos Graxos/química , Ácidos Graxos/isolamento & purificação , Ácidos Graxos/farmacologia , Frutas/química , Alimento Funcional/provisão & distribuição , Humanos , Oxirredução , Fenóis/química , Fenóis/isolamento & purificação , Fenóis/farmacologia , Fitosteróis/química , Fitosteróis/isolamento & purificação , Fitosteróis/farmacologia , Picratos/antagonistas & inibidores , Óleos Vegetais/química , Análise de Componente Principal , Solventes/química , Sonicação/métodos
13.
Int J Mol Sci ; 22(16)2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34445416

RESUMO

The antioxidant and anti-inflammatory potentials of polyphenols contained in Gynura procumbens (GP) extract were systematically analyzed. Polyphenols in GP were analyzed for nine peaks using high-performance liquid chromatography (HPLC) combined with mass spectrometry (MS), and quantitatively determined through each standard. A total of nine polyphenolic compounds were identified in the samples and their MS data were tabulated. To determine the potential of bioactive ingredients targeting DPPH and COX-2, we analyzed them by ultrafiltration combined with LC. The results identified the major compounds exhibiting binding affinity for DPPH and COX-2. Caffeic acid, kynurenic acid, and chlorogenic acid showed excellent binding affinity to DPPH and COX-2, suggesting that they can be considered as major active compounds. Additionally, the anti-inflammatory effect of GP was confirmed in vitro. This study will not only be used to provide basic data for the application of GP to the food and pharmaceutical industries, but will also provide information on effective screening methods for other medicinal plants.


Assuntos
Anti-Inflamatórios/análise , Antioxidantes/análise , Asteraceae/química , Ciclo-Oxigenase 2/metabolismo , Polifenóis/análise , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Compostos de Bifenilo/metabolismo , Cromatografia Líquida de Alta Pressão , Avaliação Pré-Clínica de Medicamentos , Humanos , Ligantes , Lipopolissacarídeos/efeitos adversos , Espectrometria de Massas , Camundongos , Picratos/metabolismo , Extratos Vegetais/química , Polifenóis/farmacologia , Células RAW 264.7
14.
Biomolecules ; 11(8)2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34439780

RESUMO

The aim of the study was to investigate changes in the content of biologically active compounds during the fermentation and aging of natural meads with the addition of three Cornelian cherry juices from three cultivars: 'Koralovyi', 'Podolski' and 'Yantarnyi', in the amount of 10% v/v. After the fermentation process the content of gallic and ellagic acids significantly increased, in relation to wort. Whereas the greatest losses were observed among unstable anthocyanins. The three-month aging process also reduced the content of the analyzed compounds except for ellagic acid, the content of which increased by up to 90%. The content of biologically active compounds, including iridoids and antioxidant phenolics, are constantly changing in the process of fermentation and aging of fruit meads. The studies proved that the addition of Cornelian cherry juice allows significantly enriched classic meads with new biologically active compounds, such as: exceptional iridoids (loganic acid, cornuside, loganine, sweroside), flavonols, phenolic acids and anthocyanins.


Assuntos
Bebidas Alcoólicas/análise , Tecnologia de Alimentos/métodos , Mel/análise , Iridoides/química , Fenóis/química , Saccharomyces/metabolismo , Antocianinas/biossíntese , Antocianinas/química , Antocianinas/classificação , Antocianinas/isolamento & purificação , Antioxidantes/química , Antioxidantes/classificação , Antioxidantes/isolamento & purificação , Antioxidantes/metabolismo , Benzotiazóis/antagonistas & inibidores , Compostos de Bifenilo/antagonistas & inibidores , Ácido Elágico/química , Ácido Elágico/isolamento & purificação , Ácido Elágico/metabolismo , Fermentação , Flavonóis/química , Flavonóis/classificação , Flavonóis/isolamento & purificação , Flavonóis/metabolismo , Frutas/química , Sucos de Frutas e Vegetais/análise , Ácido Gálico/química , Ácido Gálico/isolamento & purificação , Ácido Gálico/metabolismo , Humanos , Iridoides/classificação , Iridoides/isolamento & purificação , Iridoides/metabolismo , Fenóis/classificação , Fenóis/isolamento & purificação , Fenóis/metabolismo , Picratos/antagonistas & inibidores , Prunus avium/química , Ácido Quínico/análogos & derivados , Ácido Quínico/química , Ácido Quínico/isolamento & purificação , Ácido Quínico/metabolismo , Ácidos Sulfônicos/antagonistas & inibidores
15.
Phytomedicine ; 91: 153692, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34411834

RESUMO

PURPOSE: Magnolol (MA) exhibits anti-depressant effect by inhibiting inflammation. However, its effect on microglia polarization remains not fully understood. Herein, our study was performed to evaluate the effect of MA on microglia polarization in chronic unpredictable mild stress (CUMS)-induced depression and explore its potential mechanism. STUDY DESIGN: The CUMS procedure was conducted, and the mice were intragastrically treated with MA. BV2 cells were pretreated with MA prior to LPS/ATP challenge. METHODS: The levels of TNF-α, IL-1ß, IL-6 and IL-4, IL-10 in brain and BV2 cells were examined by ELISA. The mRNA expressions of Arg1, Ym1, Fizz1 and Klf4 in brains were measured. ROS content was determined using flow cytometry. Immunofluorescence was employed to evaluate Iba-1 level, Nrf2 nuclear translocation, Iba-1+CD16/32+ and Iba-1+CD206+ cell population. The protein expressions of Nrf2, HO-1, NLRP3, caspase-1 p20 and IL-1ß in brains and BV2 cells were investigated by western blot. Nrf2 siRNA was induced in experiments to explore the role of Nrf2 in MA-mediated microglia polarization. The ubiquitination of Nrf2 was visualized by Co-IP. RESULTS: The treatment with MA notably relieved depressive like behaviors, suppressed pro-inflammatory cytokines, promoted anti-inflammatory cytokines and the transcription of M2 phenotype microglia-specific indicators. MA upregulated the expression of Nrf2, HO-1, downregulated the expression of NLRP3, caspase-1 p20, IL-1ß both in vivo and in vitro. MA also reduced ROS concentration, promoted Nrf2 nucleus translocation and prevented Nrf2 ubiquitination. Nrf2 Knockdown by siRNA abolished the MA-mediated microglia polarization. CONCLUSION: The present research demonstrated that MA attenuated CUMS-stimulated depression by inhibiting M1 polarization and inducing M2 polarization via Nrf2/HO-1/NLRP3 signaling.


Assuntos
Compostos de Bifenilo/farmacologia , Depressão/tratamento farmacológico , Lignanas/farmacologia , Microglia , Transdução de Sinais/efeitos dos fármacos , Animais , Polaridade Celular , Heme Oxigenase-1 , Lipopolissacarídeos , Proteínas de Membrana , Camundongos , Microglia/citologia , Microglia/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR
16.
Fish Shellfish Immunol ; 117: 311-319, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34418558

RESUMO

Echinoid pigments have various biological properties such as antioxidant, cytotoxic, and antibacterial activities. We aimed to evaluate the extraction of cell-free coelomic fluid (CFCF) and coelomocyte lysate (CL) as well as qualitatively and quantitatively identify the coelomic fluid of Echinometra mathaei as a new source of polyhydroxylatednaphthoquinone (PHNQ) antioxidant pigments. Based on the High Performance liquid chromatography-electrospray mass spectrometry (HPLC-MS) analysis in negative mode, the main quinonoid (PHNQ) pigments were identified and quantified. This study also illustrated the total ion current chromatograms and related mass spectra of Spinochrome A, Spinochrome B, Spinochrome C, and Echinochrome A in CL and SpinochromeC in CFCF samples. The ions at 221, 279, 265 and 263 m/z correspond to the pseudo-molecular [M - H] ions of Spinochrome B, Spinochrome C, Echinochrome A, and Spinochrome A, respectively. These components have previously been noted from the shells and spines of sea urchins but identification of PHNQs pigments in CL and CFCF of E. mathaei using LC-MS was introduced for the first time. The results also showed that, the highest DPPH radical scavenging activity of CFCF (88.12 DPPH% scavenging at 70 µg/mL, IC50 = <10 µg/mL). The findings clearly suggest that the coelomic fluid of E. mathaei could be served as the promising as well as potential natural antioxidants in the medical and pharmaceutical industries and could replace the increasing prices of the commercial antioxidants products.


Assuntos
Antioxidantes , Naftoquinonas , Pigmentos Biológicos , Ouriços-do-Mar , Animais , Antioxidantes/química , Compostos de Bifenilo/química , Naftoquinonas/química , Picratos/química , Pigmentos Biológicos/química
17.
J Pharm Biomed Anal ; 205: 114300, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34365191

RESUMO

4'-(azidomethyl)-[1,1'-biphenyl]-2-carbonitrile (GTI-azide-1) and 5-(4'-(azidomethyl)-[1,1'-biphenyl]-2-yl)-1H-tetrazole (GTI-azide-2) are potentially genotoxic impurities that can be present at trace levels in the active pharmaceutical ingredients and drug products of sartans containing a tetrazole group. A method of high-performance liquid chromatography coupled with mass spectrometry, that allows the determination of those genotoxic impurities at sub-ppm level relative to the active pharmaceutical ingredient, was developed. The method utilises a very efficient liquid chromatograph Waters Acquity I-Class coupled with a highly sensitive tandem mass spectrometer Xevo TQ-XS. The separation was achieved on a column Acquity UPLC BEH Shield RP18 1.7 µm employing a linear elution gradient. The mass spectrometer was used with a heated electrospray ionization. The method was found to be sufficient in terms of sensitivity, linearity, precision, accuracy, selectivity and robustness and is easily applicable in the pharmaceutical quality control environment. The method allows for accurate quantification of both impurities GTI-azide-1 and GTI-azide-2 at levels below 1/10th of the specification limit, which is crucial in the context of pharmaceutical analysis. The limit of quantification was determined to be 0.033 ppm and 0.025 ppm for GTI-azide-1 and GTI-azide-2, respectively.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II , Preparações Farmacêuticas , Compostos de Bifenilo , Cromatografia Líquida de Alta Pressão , Dano ao DNA , Limite de Detecção , Reprodutibilidade dos Testes , Tetrazóis
18.
Vet Microbiol ; 260: 109186, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34333402

RESUMO

Replication of peste des petits ruminants virus (PPRV) strongly depends on the cellular environment and resources of host cells including nucleoside pool. Thus, enzymes involved in nucleoside biosynthesis (such as pyrimidine biosynthesis pathway) are regarded as attractive targets for antiviral drug development. Here, we demonstrate that brequinar (BQR) and leflunomide (LFM) which are two specific inhibitors of DHODH enzyme and 6-azauracil (6-AU) which is an ODase enzyme inhibitor robustly inhibit PPRV replication in HEK293T cell line as well as in peripheral blood mononuclear cells isolated from goat. We further demonstrate that these agents exert anti-PPRV activity via the depletion of purimidine nucleotide. Interestingly, these inhibitors can trigger the transcription of antiviral interferon-stimulated genes (ISGs). However, the induction of ISGs is largely independent of the classical JAK-STAT pathway. Combination of BQR with interferons (IFNs) exerts enhanced ISG induction and anti-PPRV activity. Taken together, this study reveals an unconventional novel mechanism of crosstalk between nucleotide biosynthesis pathways and cellular antiviral immunity in inhibiting PPRV replication. In conclusion, targeting pyrimidine biosynthesis represents a potential strategy for developing antiviral strategies against PPRV.


Assuntos
Antivirais/farmacologia , Inibidores Enzimáticos/farmacologia , Nucleosídeos/metabolismo , Peste dos Pequenos Ruminantes/virologia , Vírus da Peste dos Pequenos Ruminantes/fisiologia , Animais , Compostos de Bifenilo/farmacologia , Células HEK293 , Humanos , Imunidade Celular , Interferons/farmacologia , Leflunomida/farmacologia , Leucócitos Mononucleares/imunologia , Vírus da Peste dos Pequenos Ruminantes/efeitos dos fármacos , Vírus da Peste dos Pequenos Ruminantes/imunologia , Pirimidinas/metabolismo , Uracila/análogos & derivados , Uracila/farmacologia , Replicação Viral
19.
Nat Chem ; 13(9): 836-842, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34341526

RESUMO

While metathesis reactions involving carbon-carbon double bonds, namely olefin metathesis, have been well established with broad utility in organic synthesis and materials science, direct metathesis of kinetically less accessible C-C single bonds is extremely rare. Here we report a ruthenium-catalysed reversible C-C single-bond metathesis reaction that allows redox- and pH-neutral biaryl synthesis. Assisted by directing groups, unstrained homo-biaryl compounds undergo aryl exchanges to generate cross-biaryl products, catalysed by a well-defined air-stable ruthenium(II) complex. Functional groups reactive under typical cross-coupling reactions, such as halogen, silyl and boronate moieties, are compatible under the metathesis conditions. Mechanistic studies disclose an intriguing 'olefin-metathesis-like' pathway that involves an unexpected heptacoordinated, 18-electron closed-shell intermediate. The distinct reaction mode discovered here is expected to inspire the development of more general C-C single-bond metathesis and orthogonal cross-coupling reactions.


Assuntos
Compostos de Bifenilo/síntese química , Catálise , Complexos de Coordenação/química , Teoria da Densidade Funcional , Modelos Químicos , Oxirredução , Rutênio/química
20.
Phytomedicine ; 90: 153647, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34362632

RESUMO

BACKGROUND: Honokiol is a pleiotropic compound which been isolated from Magnolia species such as Magnolia grandiflora and Magnolia dealbata. Magnolia species Magnolia grandiflora is used in traditional medicine for the treatment of various diseases. PURPOSE: The objective of this review is to summarize the pharmacological potential and therapeutic insights of honokiol. STUDY DESIGN: Honokiol has been specified as a novel alternative to treat various disorders such as liver cancer, neuroprotective, anti-spasmodic, antidepressant, anti-tumorigenic, antithrombotic, antimicrobial, analgesic properties and others. Therefore, this study designed to represent the in-depth therapeutic potential of honokiol. METHODS: Literature searches in electronic databases, such as Web of Science, Science Direct, PubMed, Google Scholar, and Scopus, were performed using the keywords 'Honokiol', 'Health Benefits' and 'Therapeutic Insights' as the keywords for primary searches and secondary search terms were used as follows: 'Anticancer', 'Oxidative Stress', 'Neuroprotective', 'Antimicrobial', 'Cardioprotection', 'Hepatoprotective', 'Anti-inflammatory', 'Arthritis', 'Reproductive Disorders'. RESULTS: This promising bioactive compound presented an wide range of therapeutic and biological activities which include liver cancer, neuroprotective, anti-spasmodic, antidepressant, anti-tumorigenic, antithrombotic, antimicrobial, analgesic properties, and others. Its pharmacokinetics has been established in experimental animals, while in humans, this is still speculative. Some of its mechanism for exhibiting its pharmacological effects includes apoptosis of diseased cells, reduction in the expression of defective proteins like P-glycoproteins, inhibition of oxidative stress, suppression of pro-inflammatory cytokines (TNF-α, IL-10 and IL-6), amelioration of impaired hepatic enzymes and reversal of morphological alterations, among others. CONCLUSION: All these actions displayed by this novel compound could make it serve as a lead in the formulation of drugs with higher efficacy and negligible side effects utilized in the treatment of several human diseases.


Assuntos
Compostos de Bifenilo , Lignanas , Magnolia , Animais , Compostos de Bifenilo/farmacologia , Humanos , Lignanas/farmacologia , Magnolia/química , Extratos Vegetais/farmacologia
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