RESUMEN
In this paper, we complement our previous study on the antiproliferative activity of Calea fruticosa (Asteraceae) by isolating the compounds apigenin-4',7-dimethyl ether (1), budlein A (2), quercetin (3), and cichoriin (4) from the plant's aerial parts. The antiproliferative activity of these compounds was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method against human tumor cell lines. Compound 3 displayed moderate antiproliferative activity in three cell lines (HCT-116, PC-3, and SF-295, with cell growth inhibition values of 72.97, 74.55, and 68.94%) and high antiproliferative activity (90.86%) in the HL-60 cell line. The in vitro sun protection factor (SPF) of the extracts and compound 4, with and without sunscreen, was determined by a spectrophotometric method. The ethanol extract exhibited the highest SPF (9.67) at a concentration of 0.100 mg/mL, while compound 4, isolated from this extract, showed a SPF of 13.79 at the same concentration. A relative increased efficacy of SPF was observed for the extracts and compound 4 when sunscreen was also used. Compound 4 has not been reported previously from any species within the genus Calea. Compounds 1-4 were obtained from this species for the first time.
Asunto(s)
Asteraceae , Extractos Vegetales , Sustancias Protectoras , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , HumanosRESUMEN
INTRODUÇÃO: A morte súbita cardíaca (MSC) corresponde a 5% dos óbitos na população. Até 80% dos casos ocorrem em portadores de doença isquêmica. Na atualidade, o parâmetro utilizado com este fim é a fração de ejeção ventricular esquerda (FEVE). Nas últimas décadas, parâmetros de repolarização ventricular se mostraram ferramentas úteis na estratificação deste risco em diversas patologias. MÉTODOS: Estudo transversal, que incluiu 177 portadores de doença coronária e foram submetidos a estudo eletrofisiológico (EEF) em um hospital terciário entre 2013-2017, e teve por OBJETIVO: avaliar a associação entre parâmetros eletrocardiográficos de repolarização ventricular e indução de arritmias ventriculares malignas (AVM) nos grupos com FEVE maior e menor do que 35%. RESULTADOS: A amostra apresentou idade média de 65 anos, predomínio do gênero masculino (83,6%) e FEVE média de 37,5%. Em relação a eventos prévios, 76,8% dos pacientes apresentaram síndrome coronária e 16,9%, MSC abortada. AVM foram induzidas em 75 indivíduos (42,4%). Análise multivariada demonstrou que o intervalo QT associou-se ao desfecho, com aumento de 7% na chance de indução de arritmia a cada incremento de 10ms. Em contrapartida, os intervalos QT corrigido e T pico-fim, suas dispersões e a relação QT/T pico-fim não apresentaram tal relação. Curva ROC evidenciou que QT > 452ms possui acurácia de 0,611 (p=0,011) para predizer indução de AVM, com OR=2,7 (p=0,04). No que diz respeito aos indivíduos com FEVE < 35%, análise univariada demonstrou que nenhum dos parâmetros de repolarização ventricular relacionou-se com a indutibilidade arrítmica. Quando avaliadas conjuntamente as variáveis FEVE e intervalo QT, utilizando o ponto de corte de 452 ms, verificou-se que o prolongamento do parâmetro eletrocardiográfico associado à disfunção ventricular importante aumentou o risco do desfecho (p=0,0003) e, em análise multivariada, apresentou OR=5,44 (p=0,0004). No tangente aos pacientes com FEVE = 35%, a dispersão do QT foi significativamente maior naqueles com indução de arritmia; tal associação não foi verificada nas demais variáveis. A curva ROC demonstrou que valores > 20ms obtiveram acurácia de 0,638 na predição do desfecho. CONCLUSÃO: O intervalo QT relaciona-se à indução de AVM durante EEF em pacientes portadores de doença coronária, e valores acima 452 ms demonstraram moderada capacidade preditiva para este desfecho, especialmente quando associado a FEVE < 35%. A dispersão do QT foi um fator de risco com acurácia intermediária para predição naqueles com FEVE = 35%.
Asunto(s)
Arritmias Cardíacas , Síndrome de QT Prolongado , ElectrofisiologíaRESUMEN
INTRODUÇÃO A morte súbita cardíaca (MSC) corresponde a 5% dos óbitos na população geral e sua predição representa um desafio na prática clínica. Até 80% dos casos de MSC ocorrem em portadores de doença isquêmica. Na atualidade, o parâmetro utiliza do com este propósito é a fração de ejeção ventricular esquerda (FEVE), a qual possui sensibilidade limitada, já que a maioria dos casos de MSC ocorre em pacientes sem disfunção significativa. Nas últimas décadas, parâmetros de repolarização ventricular se mostraram ferramentas úteis na estratificação do risco de morte em diversas patologias, entretanto as evidências sobre suas capacidades preditivas são controversas na literatura. Objetivo e métodos Estudo transversal, que incluiu 177 portadores de doença arterial coronária e foram submetidos a estudo eletrofisiológico (EEF) em um hospital terciário entre 2013 e 2017, e teve por objetivo avaliar a associação entre parâmetros eletrocardiográficos de repolarização ventricular e indução de arritmias ventriculares malignas (AVM) durante estimulação elétrica programada nos grupos com e sem evento coronário prévio. Resultados A amostra em estudo apresentou idade média de 65 anos, predomínio de indivíduos do gênero masculino (83,6%) e FEVE média de 37,5%. Em relação a eventos clínicos prévios, 76,8% dos pacientes já apresentaram síndrome coronária e 16,9%, MSC abortada. AVM foram induzidas em 75 indivíduos (42,4%) durante o procedimento. Análise multivariada demonstrou que o intervalo QT medido associou-se a este desfecho (p=0,013). Em contrapartida, os intervalos QT corrigido e T pico-fim, suas dispersões e a relação QT/T pico-fim não apresentaram tal relação. Ajuste da curva ROC evidenciou que um QT > 432 ms possui acurácia de 0,628 (p=0,009) para predizer indução de AVM durante EEF em portadores de síndrome coronária prévia. No que tange aos pacientes que não apresentaram evento anteriormente, nenhum dos parâmetros avaliados demonstrou associação com o desfecho. Conclusão O intervalo QT medido relaciona-se à indução de AVM durante EEF em pacientes portadores de doença arterial coronária com evento agudo prévio, e valores acima 432 ms demonstraram moderada capacidade preditiva para este desfecho.
Asunto(s)
Síncope , Síndrome de QT Prolongado , PredicciónRESUMEN
In this paper, we complement our previous study on the antiproliferative activity of Calea fruticosa (Asteraceae) by isolating the compounds apigenin-4',7-dimethyl ether (1), budlein A (2), quercetin (3), and cichoriin (4) from the plant's aerial parts. The antiproliferative activity of these compounds was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method against human tumor cell lines. Compound 3 displayed moderate antiproliferative activity in three cell lines (HCT-116, PC-3, and SF-295, with cell growth inhibition values of 72.97, 74.55, and 68.94%) and high antiproliferative activity (90.86%) in the HL-60 cell line. The in vitro sun protection factor (SPF) of the extracts and compound 4, with and without sunscreen, was determined by a spectrophotometric method. The ethanol extract exhibited the highest SPF (9.67) at a concentration of 0.100 mg/mL, while compound 4, isolated from this extract, showed a SPF of 13.79 at the same concentration. A relative increased efficacy of SPF was observed for the extracts and compound 4 when sunscreen was also used. Compound 4 has not been reported previously from any species within the genus Calea. Compounds 1-4 were obtained from this species for the first time.
Asunto(s)
Humanos , Extractos Vegetales , Asteraceae , Sustancias Protectoras , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacosRESUMEN
PURPOSE: To determine the effect of short-term 4 mg/mL dexamethasone solution treatment in diabetic macular edema (DME). PATIENTS AND METHODS: Twenty-seven pseudophakic diabetic patients with visual impairment caused by DME were randomized to receive 0.01 mL (40 µg), 0.03 mL (120 µg) or 0.05 mL (200 µg) intravitreal dexamethasone solution. Eyes were evaluated in terms of macular thickness, best-corrected visual acuity (BCVA) and intraocular pressure (IOP) at 3, 7 and 28 days after injection (D). RESULTS: There was a significant reduction in macular thickness between D0 and D3 for all groups (0.01 mL - P=0.008, 0.03 mL - P=0.038, and 0.05 mL - P=0.008). Between D0 and D7, a significant reduction in macular thickness was observed in 0.01 mL and 0.05 mL groups (0.01 mL - P=0.013 and 0.05 mL - P=0.021). Between D0 and D28, no significant reduction of macular thickness was observed for any group. Between D0 and D3, a significant improvement in BCVA in the 0.03 mL group (P=0.028) was observed. Between D0 and D7, a significant improvement in BCVA was observed in 0.01 mL and 0.03 mL groups (0.01 mL - P=0.018 and 0.03 mL - P=0.027). Between D0 and D28, a significant improvement in BCVA was observed for the 0.01 mL group (P=0.017). No significant differences in IOP measurements were observed for any group. Safety analysis revealed no serious ocular or systemic events. CONCLUSION AND RELEVANCE: Intravitreal dexamethasone solution is effective in reducing macular thickness secondary to DME in the short-term. Improvement in short-term visual acuity was observed. Although DME requires long-term treatment, it may be a low cost therapeutic option used in specific short-term situations.Trial registration: NCT03608839 (http://www.clinicaltrials.gov).
RESUMEN
Uma avestruz-do-pescoço-vermelho, com dois anos de idade, apresentava um nódulo no terço médio do esôfago e foi submetida a procedimento cirúrgico. Histologicamente, observou-se uma área focalmente extensa de necrose estendendo-se da túnica mucosa à muscular, e, em algumas secções, à túnica adventícia. Circundando a área de necrose, observou-se uma reação inflamatória composta principalmente por granulócitos e macrófagos, associada à fibroplasia e neovascularização. Em meio às áreas de necrose e inflamação, verificavam-se numerosas imagens negativas de hifas em seções longitudinais e transversais, melhor apreciadas pela coloração de metenamina nitrato de prata de Grocott. O diagnóstico definitivo de infecção por Pythium insidiosum foi confirmado por imuno-histoquímica. A avestruz recebia água para consumo de um lago localizado em uma área de pastagem, no qual alguns cavalos haviam desenvolvido pitiose cutânea anteriormente.(AU)
Asunto(s)
Animales , Enfermedades de las Aves , Trastornos de Deglución/veterinaria , Struthioniformes , Esofagitis/veterinaria , Pitiosis/diagnósticoRESUMEN
Uma avestruz-do-pescoço-vermelho, com dois anos de idade, apresentava um nódulo no terço médio do esôfago e foi submetida a procedimento cirúrgico. Histologicamente, observou-se uma área focalmente extensa de necrose estendendo-se da túnica mucosa à muscular, e, em algumas secções, à túnica adventícia. Circundando a área de necrose, observou-se uma reação inflamatória composta principalmente por granulócitos e macrófagos, associada à fibroplasia e neovascularização. Em meio às áreas de necrose e inflamação, verificavam-se numerosas imagens negativas de hifas em seções longitudinais e transversais, melhor apreciadas pela coloração de metenamina nitrato de prata de Grocott. O diagnóstico definitivo de infecção por Pythium insidiosum foi confirmado por imuno-histoquímica. A avestruz recebia água para consumo de um lago localizado em uma área de pastagem, no qual alguns cavalos haviam desenvolvido pitiose cutânea anteriormente.(AU)
Asunto(s)
Animales , Enfermedades de las Aves , Trastornos de Deglución/veterinaria , Struthioniformes , Esofagitis/veterinaria , Pitiosis/diagnósticoRESUMEN
This study was carried out to assess the antibacterial, cytotoxic and antioxidant activities of extracts of Morus nigra L. HPLC was used to determine the fingerprint chromatogram of the crude ethanolic extract (Mn-EtOH). The antibacterial effect was assessed through the method of microdilution. The cytotoxicity was tested against human tumour cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents were also assessed through the Folin-Ciocalteu and aluminum chloride methods, respectively. Antioxidant activities of the extracts were evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging and β-carotene-linoleic acid bleaching methods. The presence of phenolic compounds in Mn-EtOH was confirmed using HPLC. The extracts showed activity against most microorganisms tested. The extracts did not show any expressive antiproliferative effect in the assessment of cytotoxicity. The most significant total phenolic content was 153.00 ± 11.34 mg of gallic acid equivalent/g to the ethyl acetate extract (AcOEt). The total flavonoid content was 292.50 ± 70.34 mg of catechin equivalent/g to the AcOEt extract, which presented the best antioxidant activity (IC50 50.40 ± 1.16 μg/mL) for DPPH scavenging. We can conclude that this species shows strong antibacterial and antioxidant activities, as well as weak cytotoxic effects.(AU)
Este estudo foi realizado para avaliar as atividades antibacteriana, citotóxica e antioxidante de extratos de Morus nigra L. HPLC foi utilizado para determinar o perfil de compostos fenólicos do extrato etanólico bruto (Mn-EtOH). O efeito antibacteriano foi avaliado através do método de microdiluição. A citotoxicidade foi testada contra linhagens celulares de tumores humanos utilizando o ensaio do brometo de 3-(4,5-dimetil-2-tiazolil)-2,5-difenil-2H-tetrazólio (MTT). O conteúdo total de compostos fenólicos e flavonoides também foi avaliado por meio dos métodos de Folin-Ciocalteu e cloreto de alumínio, respectivamente. A atividade antioxidante dos extratos foi avaliada por meio do sequestro do radical livre 2,2-difenil-1-picrilhidrazil (DPPH) e co-oxidação do sistema β-caroteno-ácido linoleico. A presença de compostos fenólicos em Mn-EtOH foi confirmada utilizando HPLC. Os extratos mostraram atividade contra a maioria dos microrganismos testados. Os extratos não mostraram qualquer efeito antiproliferativo expressivo na avaliação da citotoxicidade. O conteúdo fenólico total mais significativo foi de 153,00 ± 11,34 mg de equivalente de ácido gálico/g para o extrato acetato de etila (AcOEt). O conteúdo de flavonoides totais foi de 292,50 ± 70,34 mg de equivalente de catequina/g para o extrato AcOEt, que apresentou a melhor atividade antioxidante (IC50 50,40 ± 1,16 mg/mL) para o sequestro do DPPH. Podemos concluir que esta espécie apresenta forte atividade antibacteriana e antioxidante, bem como fraca atividade citotóxica.(AU)
Asunto(s)
Morus , Extractos Vegetales/uso terapéutico , Antibacterianos/análisis , Antioxidantes/análisisRESUMEN
Abstract This study was carried out to assess the antibacterial, cytotoxic and antioxidant activities of extracts of Morus nigra L. HPLC was used to determine the fingerprint chromatogram of the crude ethanolic extract (Mn-EtOH). The antibacterial effect was assessed through the method of microdilution. The cytotoxicity was tested against human tumour cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents were also assessed through the Folin-Ciocalteu and aluminum chloride methods, respectively. Antioxidant activities of the extracts were evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging and β-carotene-linoleic acid bleaching methods. The presence of phenolic compounds in Mn-EtOH was confirmed using HPLC. The extracts showed activity against most microorganisms tested. The extracts did not show any expressive antiproliferative effect in the assessment of cytotoxicity. The most significant total phenolic content was 153.00 ± 11.34 mg of gallic acid equivalent/g to the ethyl acetate extract (AcOEt). The total flavonoid content was 292.50 ± 70.34 mg of catechin equivalent/g to the AcOEt extract, which presented the best antioxidant activity (IC50 50.40 ± 1.16 μg/mL) for DPPH scavenging. We can conclude that this species shows strong antibacterial and antioxidant activities, as well as weak cytotoxic effects.
Resumo Este estudo foi realizado para avaliar as atividades antibacteriana, citotóxica e antioxidante de extratos de Morus nigra L. HPLC foi utilizado para determinar o perfil de compostos fenólicos do extrato etanólico bruto (Mn-EtOH). O efeito antibacteriano foi avaliado através do método de microdiluição. A citotoxicidade foi testada contra linhagens celulares de tumores humanos utilizando o ensaio do brometo de 3-(4,5-dimetil-2-tiazolil)-2,5-difenil-2H-tetrazólio (MTT). O conteúdo total de compostos fenólicos e flavonoides também foi avaliado por meio dos métodos de Folin-Ciocalteu e cloreto de alumínio, respectivamente. A atividade antioxidante dos extratos foi avaliada por meio do sequestro do radical livre 2,2-difenil-1-picrilhidrazil (DPPH) e co-oxidação do sistema β-caroteno-ácido linoleico. A presença de compostos fenólicos em Mn-EtOH foi confirmada utilizando HPLC. Os extratos mostraram atividade contra a maioria dos microrganismos testados. Os extratos não mostraram qualquer efeito antiproliferativo expressivo na avaliação da citotoxicidade. O conteúdo fenólico total mais significativo foi de 153,00 ± 11,34 mg de equivalente de ácido gálico/g para o extrato acetato de etila (AcOEt). O conteúdo de flavonoides totais foi de 292,50 ± 70,34 mg de equivalente de catequina/g para o extrato AcOEt, que apresentou a melhor atividade antioxidante (IC50 50,40 ± 1,16 mg/mL) para o sequestro do DPPH. Podemos concluir que esta espécie apresenta forte atividade antibacteriana e antioxidante, bem como fraca atividade citotóxica.
Asunto(s)
Humanos , Extractos Vegetales/farmacología , Morus/química , Antibacterianos/farmacología , Antioxidantes/farmacología , Fenoles/análisis , Picratos/metabolismo , Flavonoides/análisis , Compuestos de Bifenilo/metabolismo , Extractos Vegetales/toxicidad , Extractos Vegetales/química , Supervivencia Celular/efectos de los fármacos , Línea Celular Tumoral , Antibacterianos/toxicidad , Antibacterianos/química , Antioxidantes/toxicidad , Antioxidantes/químicaRESUMEN
The use of natural products in therapeutics has been growing over the years. Lignans are compounds with large pharmaceutical use, which has aroused interest in the search for new drugs to treat diseases. The present study evaluated the cytotoxicity of (-)-trachelogenin, a dibenzylbutyrolactone type lignan isolated from Combretum fruticosum, against several tumor and non-tumor cell lines using the MTT assay and its possible mechanism of action. (-)-Trachelogenin showed IC50 values ranging of 0.8-32.4µM in SF-295 and HL-60 cell lines, respectively and IC50 values >64µM in non-tumor cell lines. (-)-trachelogenin persistently induced autophagic cell death, with cytoplasmic vacuolization and formation of autophagosomes mediated by increasing LC3 activation and altering the expression levels of Beclin-1.
Asunto(s)
4-Butirolactona/análogos & derivados , Antineoplásicos Fitogénicos/farmacología , Autofagia/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Combretum/química , Descubrimiento de Drogas , Tallos de la Planta/química , 4-Butirolactona/efectos adversos , 4-Butirolactona/química , 4-Butirolactona/aislamiento & purificación , 4-Butirolactona/farmacología , Antineoplásicos Fitogénicos/efectos adversos , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Autofagosomas/efectos de los fármacos , Autofagosomas/patología , Beclina-1/agonistas , Beclina-1/metabolismo , Brasil , Línea Celular , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/patología , Combretum/crecimiento & desarrollo , Etnofarmacología , Células HCT116 , Humanos , Concentración 50 Inhibidora , Medicina Tradicional , Proteínas Asociadas a Microtúbulos/agonistas , Proteínas Asociadas a Microtúbulos/metabolismo , Estructura Molecular , Proteínas de Neoplasias/agonistas , Proteínas de Neoplasias/metabolismo , Tallos de la Planta/crecimiento & desarrollo , Vacuolas/efectos de los fármacos , Vacuolas/patologíaRESUMEN
This study was carried out to assess the antibacterial, cytotoxic and antioxidant activities of extracts of Morus nigra L. HPLC was used to determine the fingerprint chromatogram of the crude ethanolic extract (Mn-EtOH). The antibacterial effect was assessed through the method of microdilution. The cytotoxicity was tested against human tumour cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents were also assessed through the Folin-Ciocalteu and aluminum chloride methods, respectively. Antioxidant activities of the extracts were evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging and ß-carotene-linoleic acid bleaching methods. The presence of phenolic compounds in Mn-EtOH was confirmed using HPLC. The extracts showed activity against most microorganisms tested. The extracts did not show any expressive antiproliferative effect in the assessment of cytotoxicity. The most significant total phenolic content was 153.00 ± 11.34 mg of gallic acid equivalent/g to the ethyl acetate extract (AcOEt). The total flavonoid content was 292.50 ± 70.34 mg of catechin equivalent/g to the AcOEt extract, which presented the best antioxidant activity (IC50 50.40 ± 1.16 µg/mL) for DPPH scavenging. We can conclude that this species shows strong antibacterial and antioxidant activities, as well as weak cytotoxic effects.
Asunto(s)
Antibacterianos/farmacología , Antioxidantes/farmacología , Morus/química , Extractos Vegetales/farmacología , Antibacterianos/química , Antibacterianos/toxicidad , Antioxidantes/química , Antioxidantes/toxicidad , Compuestos de Bifenilo/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Flavonoides/análisis , Humanos , Fenoles/análisis , Picratos/metabolismo , Extractos Vegetales/química , Extractos Vegetales/toxicidadRESUMEN
Chronic kidney disease (CKD) is a relevant disease in feline clinic. The tubulointerstitial damage, with collagen deposition and fibrosis, is an important result of this process. The aim of this study was to quantify and correlate the deposition of collagen and severity of interstitial fibrosis (IF) in the kidney from cats in different stages of CKD. Kidney fragments from 10 adult cats with CKD were analyzed and stained by Masson's trichrome (MT) and Picrosirius red (PSR) for circular polarized microscopy. Random quantitative analysis was performed on MT sections to classify the degree of IF, per field area, with and without circular polarization. Statistics correlations were performed by Spearman's (ρ; p < .05). There was a significant correlation of IF quantification with the area of interstitial collagen deposition by polarized PSR (PSRp) (r = .7939, p = .0098) and nonpolarized PSR (PSRn) (r = .7781, p = .0080). There was a positive correlation of serum creatinine (sCr) at different stages of CKD with PSRp (r = .7939, p = .0098), PSRn (r = .8667, p = .0027) and MT (r = .7818, p = .0117). Correlations between the percentage of quantified area was also positive from PSRp to PSRn (r = .9030, p = .0009) and PSRp to MT (r = .7939, p = .0098). The PSRN was also correlated with MT (r = .9273, p = .0001). The correlation with IF and sCr follows the disease evolution and the quantification of collagen by PSR is an excellent tool for analyzing the disease severity at different stages.
Asunto(s)
Compuestos Azo/química , Enfermedades de los Gatos/patología , Colágeno/análisis , Colorantes/química , Microscopía de Polarización/métodos , Insuficiencia Renal Crónica/veterinaria , Animales , Enfermedades de los Gatos/diagnóstico , Gatos , Colágeno/ultraestructura , Creatinina/sangre , Femenino , Fibrosis , Riñón/química , Riñón/patología , Riñón/ultraestructura , Masculino , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/patología , Índice de Severidad de la EnfermedadRESUMEN
Two novel compounds bearing heterocyclic nitrogen, 2-pyridone alkaloid (1) and alloxazine derivative (2), along with the known pretenellin B (3), pyridovericin (4) and lumichrome (5) were isolated from a culture of the entomopathogenic fungal strain Beauveria bassiana. The chemical structures of 2-pyridone alkaloid and alloxazine derivative were established on the basis of the interpretation of spectroscopic data. The isolated compounds were evaluated in a panel of five cancer cell lines and pyridovericin exhibited cytotoxicity (IC50, µM) against cancer cell lines: HL-60 (25.9 ± 0.3), HCT8 (34.6 ± 3.6), MDA-MB435 (34.8 ± 3.8) and SF295 (31.1 ± 0.6). Considering that other pyridone compounds display good cytotoxic activity, it would be suggested to obtain new semi synthetic derivatives of pyridovericin, for the development of new cytotoxic chemical entities.
Asunto(s)
Alcaloides/química , Antineoplásicos/farmacología , Beauveria/química , Alcaloides/aislamiento & purificación , Alcaloides/farmacología , Antineoplásicos/química , Beauveria/metabolismo , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Flavinas/química , Flavinas/aislamiento & purificación , Humanos , Estructura Molecular , Monosacáridos/química , Piridonas/química , Piridonas/aislamiento & purificación , Piridonas/farmacología , Metabolismo SecundarioRESUMEN
Abstract This study was carried out to assess the antibacterial, cytotoxic and antioxidant activities of extracts of Morus nigra L. HPLC was used to determine the fingerprint chromatogram of the crude ethanolic extract (Mn-EtOH). The antibacterial effect was assessed through the method of microdilution. The cytotoxicity was tested against human tumour cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents were also assessed through the Folin-Ciocalteu and aluminum chloride methods, respectively. Antioxidant activities of the extracts were evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging and -carotene-linoleic acid bleaching methods. The presence of phenolic compounds in Mn-EtOH was confirmed using HPLC. The extracts showed activity against most microorganisms tested. The extracts did not show any expressive antiproliferative effect in the assessment of cytotoxicity. The most significant total phenolic content was 153.00 ± 11.34 mg of gallic acid equivalent/g to the ethyl acetate extract (AcOEt). The total flavonoid content was 292.50 ± 70.34 mg of catechin equivalent/g to the AcOEt extract, which presented the best antioxidant activity (IC50 50.40 ± 1.16 g/mL) for DPPH scavenging. We can conclude that this species shows strong antibacterial and antioxidant activities, as well as weak cytotoxic effects.
Resumo Este estudo foi realizado para avaliar as atividades antibacteriana, citotóxica e antioxidante de extratos de Morus nigra L. HPLC foi utilizado para determinar o perfil de compostos fenólicos do extrato etanólico bruto (Mn-EtOH). O efeito antibacteriano foi avaliado através do método de microdiluição. A citotoxicidade foi testada contra linhagens celulares de tumores humanos utilizando o ensaio do brometo de 3-(4,5-dimetil-2-tiazolil)-2,5-difenil-2H-tetrazólio (MTT). O conteúdo total de compostos fenólicos e flavonoides também foi avaliado por meio dos métodos de Folin-Ciocalteu e cloreto de alumínio, respectivamente. A atividade antioxidante dos extratos foi avaliada por meio do sequestro do radical livre 2,2-difenil-1-picrilhidrazil (DPPH) e co-oxidação do sistema -caroteno-ácido linoleico. A presença de compostos fenólicos em Mn-EtOH foi confirmada utilizando HPLC. Os extratos mostraram atividade contra a maioria dos microrganismos testados. Os extratos não mostraram qualquer efeito antiproliferativo expressivo na avaliação da citotoxicidade. O conteúdo fenólico total mais significativo foi de 153,00 ± 11,34 mg de equivalente de ácido gálico/g para o extrato acetato de etila (AcOEt). O conteúdo de flavonoides totais foi de 292,50 ± 70,34 mg de equivalente de catequina/g para o extrato AcOEt, que apresentou a melhor atividade antioxidante (IC50 50,40 ± 1,16 mg/mL) para o sequestro do DPPH. Podemos concluir que esta espécie apresenta forte atividade antibacteriana e antioxidante, bem como fraca atividade citotóxica.
RESUMEN
Abstract This study was carried out to assess the antibacterial, cytotoxic and antioxidant activities of extracts of Morus nigra L. HPLC was used to determine the fingerprint chromatogram of the crude ethanolic extract (Mn-EtOH). The antibacterial effect was assessed through the method of microdilution. The cytotoxicity was tested against human tumour cell lines using the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The total phenolic and flavonoid contents were also assessed through the Folin-Ciocalteu and aluminum chloride methods, respectively. Antioxidant activities of the extracts were evaluated by using 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging and -carotene-linoleic acid bleaching methods. The presence of phenolic compounds in Mn-EtOH was confirmed using HPLC. The extracts showed activity against most microorganisms tested. The extracts did not show any expressive antiproliferative effect in the assessment of cytotoxicity. The most significant total phenolic content was 153.00 ± 11.34 mg of gallic acid equivalent/g to the ethyl acetate extract (AcOEt). The total flavonoid content was 292.50 ± 70.34 mg of catechin equivalent/g to the AcOEt extract, which presented the best antioxidant activity (IC50 50.40 ± 1.16 g/mL) for DPPH scavenging. We can conclude that this species shows strong antibacterial and antioxidant activities, as well as weak cytotoxic effects.
Resumo Este estudo foi realizado para avaliar as atividades antibacteriana, citotóxica e antioxidante de extratos de Morus nigra L. HPLC foi utilizado para determinar o perfil de compostos fenólicos do extrato etanólico bruto (Mn-EtOH). O efeito antibacteriano foi avaliado através do método de microdiluição. A citotoxicidade foi testada contra linhagens celulares de tumores humanos utilizando o ensaio do brometo de 3-(4,5-dimetil-2-tiazolil)-2,5-difenil-2H-tetrazólio (MTT). O conteúdo total de compostos fenólicos e flavonoides também foi avaliado por meio dos métodos de Folin-Ciocalteu e cloreto de alumínio, respectivamente. A atividade antioxidante dos extratos foi avaliada por meio do sequestro do radical livre 2,2-difenil-1-picrilhidrazil (DPPH) e co-oxidação do sistema -caroteno-ácido linoleico. A presença de compostos fenólicos em Mn-EtOH foi confirmada utilizando HPLC. Os extratos mostraram atividade contra a maioria dos microrganismos testados. Os extratos não mostraram qualquer efeito antiproliferativo expressivo na avaliação da citotoxicidade. O conteúdo fenólico total mais significativo foi de 153,00 ± 11,34 mg de equivalente de ácido gálico/g para o extrato acetato de etila (AcOEt). O conteúdo de flavonoides totais foi de 292,50 ± 70,34 mg de equivalente de catequina/g para o extrato AcOEt, que apresentou a melhor atividade antioxidante (IC50 50,40 ± 1,16 mg/mL) para o sequestro do DPPH. Podemos concluir que esta espécie apresenta forte atividade antibacteriana e antioxidante, bem como fraca atividade citotóxica.
RESUMEN
The genus Pestivirus of the family Flaviviridae consists of four recognized species: Bovine viral diarrhoea virus 1 (BVDV-1), Bovine viral diarrhoea virus 2 (BVDV-2), Classical swine fever virus (CSFV) and Border disease virus (BDV). Recently, atypical pestiviruses ('HoBi'-like pestiviruses) were identified in batches of contaminated foetal calf serum and in naturally infected cattle with and without clinical symptoms. Here, we describe the first report of a mucosal disease-like clinical presentation (MD) associated with a 'HoBi'-like pestivirus occurring in a cattle herd. The outbreak was investigated using immunohistochemistry, antibody detection, viral isolation and RT-PCR. The sequence and phylogenetic analysis of 5'NCR, N(pro) and E2 regions of the RT-PCR positive samples showed that four different 'HoBi'-like strains were circulating in the herd. The main clinical signs and lesions were observed in the respiratory and digestive systems, but skin lesions and corneal opacity were also observed. MD characteristic lesions and a pestivirus with cytopathic biotype were detected in one calf. The present study is the first report of a MD like presentation associated with natural infection with 'HoBi'-like pestivirus. This report describes the clinical signs and provides a pathologic framework of an outbreak associated with at least two different 'HoBi'-like strains. Based on these observations, it appears that these atypical pestiviruses are most likely underdiagnosed in Brazilian cattle.
Asunto(s)
Enfermedades de los Bovinos/virología , Brotes de Enfermedades/veterinaria , Infecciones por Pestivirus/veterinaria , Pestivirus/aislamiento & purificación , Animales , Anticuerpos Antivirales/sangre , Brasil/epidemiología , Bovinos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Inmunohistoquímica/veterinaria , Pestivirus/clasificación , Infecciones por Pestivirus/diagnóstico , Infecciones por Pestivirus/virología , Filogenia , Análisis de Secuencia de ADN/veterinariaRESUMEN
Biflorin is an o-naphthoquinone isolated from the roots of the plant Capraria biflora L. (Scrophulariaceae). In this study, the cytotoxic effects of biflorin were verified, and late apoptosis was detected in various cancer cell lines by in situ analysis. The cytotoxicity was further evaluated exclusively for 48 h of treatment in different tumor and non-tumor cell lines (Hep-2, HeLa, HT-29, A-375, and A-549, and HEK-293, respectively). The results indicated that biflorin induced selective cytotoxicity in tumor cells. HeLa cells were more susceptible to biflorin, followed by HT-29, A-549, A-375, and Hep-2 at all concentrations (range 5-50 µg/mL), and the highest half-maximal inhibitory concentration IC50 (56.01 ± 1.17 µg/mL) was observed in HEK-293 cells. Late apoptotic/necrotic events, observed by in situ immunostaining with Annexin V, varied with each cell line; an increase in late apoptotic events was observed corresponding to the increase in biflorin dosage. Hep-2 cells showed a greater percentage of late apoptotic events among the tumor cell lines when treated with higher concentrations of biflorin (69.63 ± 2.28%). The non-tumor HEK-293 line showed greater resistance to late apoptotic events, as well as a lower level of cytotoxicity (77.69 ± 6.68%) than the tested tumor lines. The data presented indicate that biflorin showed an important, possibly selective, cytotoxicity against tumor cell lines, thereby revealing a promising novel substance with potential anticancer activity for tumor therapy.
Asunto(s)
Antineoplásicos Fitogénicos/administración & dosificación , Naftoquinonas/administración & dosificación , Neoplasias/tratamiento farmacológico , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Células HEK293 , Humanos , Naftoquinonas/química , Neoplasias/patología , Scrophulariaceae/químicaRESUMEN
The literature has identified complex aspects of intracellular host-parasite relationships, which require systematic, nonreductionist approaches and spatial/temporal information. Increasing and integrating temporal and spatial dimensions in host cell imaging have contributed to elucidating several conceptual gaps in the biology of intracellular parasites. To access and investigate complex and emergent dynamic events, it is mandatory to follow them in the context of living cells and organs, constructing scientific images with integrated high quality spatiotemporal data. This review discusses examples of how advances in microscopy have challenged established conceptual models of the intracellular life cycles of Leishmania spp. and Trypanosoma cruzi protozoan parasites.
Asunto(s)
Enfermedad de Chagas/patología , Interacciones Huésped-Parásitos/fisiología , Leishmania/fisiología , Leishmaniasis/patología , Trypanosoma cruzi/fisiología , Animales , Humanos , MicroscopíaRESUMEN
The effects and susceptibility of donkeys to Crotalaria juncea and Crotalaria retusa poisoning were determined at high and low doses. Seeds of C. juncea containing 0.074% of dehydropyrrolizidine alkaloids (DHPAs) (isohemijunceines 0.05%, trichodesmine 0.016%, and junceine 0.008%) were administered to three donkeys at 0.3, 0.6 and 1 g/kg body weight (g/kg) daily for 365 days. No clinical signs were observed and, on liver and lung biopsies, the only lesion was a mild liver megalocytosis in the donkeys ingesting 0.6 and 1 g/kg/day. Two other donkeys that received daily doses of 3 and 5 g seed/kg showed initial respiratory signs 70 and 40 days after the start of the administration, respectively. The donkeys were euthanized following severe respiratory signs and the main lung lesions were proliferation of Clara cells and interstitial fibrosis. Three donkeys ingested seeds of C. retusa containing 5.99% of monocrotaline at daily doses of 0.025, 0.05 and 0.1 g/kg for 365 days. No clinical signs were observed and, on liver and lung biopsies, the only lesion was moderate liver megalocytosis in each of the three donkeys. One donkey that received a single dose of 5 g/kg of C. retusa seeds and another that received 1 g/kg daily for 7 days both showed severe clinical signs and died with diffuse centrilobular liver necrosis. No lung lesions were observed. Another donkey that received a single dose of 2.5 g/kg of C. retusa seeds showed no clinical signs. The hepatic and pneumotoxic effects observed are consistent with an etiology involving DHPAs. Furthermore, the occurrence of lung or liver lesions correlates with the type of DHPAs contained in the seeds. Similarly as has been reported for horses, the data herein suggest that in donkeys some DHPAs are metabolized in the liver causing liver disease, whereas others are metabolized in the lung by Clara cells causing lung disease.
Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Crotalaria/química , Crotalaria/envenenamiento , Enfermedades Pulmonares/patología , Alcaloides de Pirrolicidina/envenenamiento , Animales , Proliferación Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Crotalaria/clasificación , Equidae , Fibrosis/inducido químicamente , Hígado/efectos de los fármacos , Hígado/patología , Pulmón/efectos de los fármacos , Pulmón/patología , Enfermedades Pulmonares/inducido químicamente , Monocrotalina/análogos & derivados , Monocrotalina/envenenamiento , Intoxicación por Plantas/patología , Intoxicación por Plantas/veterinaria , Semillas/química , Semillas/envenenamientoRESUMEN
In this study, the cytotoxicity, genotoxicity and early ROS generation of 2,2-dimethyl-(3H)-3-(N-3'-nitrophenylamino)naphtho[1,2-b]furan-4,5-dione (QPhNO(2)) were investigated and compared with those of its precursor, nor-beta-lapachone (nor-beta), with the main goal of proposing a mechanism of antitumor action. The results were correlated with those obtained from electrochemical experiments held in protic (acetate buffer pH 4.5) and aprotic (DMF/TBABF(4)) media in the presence and absence of oxygen and with those from dsDNA biosensors and ssDNA in solution, which provided evidence of a positive interaction with DNA in the case of QPhNO(2). QPhNO(2) caused DNA fragmentation and mitochondrial depolarization and induced apoptosis/necrosis in HL-60 cells. Pre-treatment with N-acetyl-l-cysteine partially abolished the observed effects related to the QPhNO(2) treatment, including those involving apoptosis induction, indicating a partially redox-dependent mechanism. These findings point to the potential use of the combination of pharmacology and electrochemistry in medicinal chemistry.