Morphological and Functional Analysis of Cardiac Ameliorations in Elderly Rats Supplemented with a Magnolol Extract Complex / Análisis Morfológico y Funcional de las Mejoras Cardíacas en Ratas Ancianas Suplementadas con un Complejo de Extracto de Magnolol

SUMMARY: Magnolia bark extract supplementation has an anti-oxidative role in mammalians. However, its role in physiological aged-associated heart insufficiency is not known yet. Therefore, we investigated the effects of a magnolia bark complex, including magnolol and honokiol components (MAHOC), in elderly rat hearts (24-month-old aged group). One group of aged rats was supplemented with MAHOC (400 mg/kg/d, for 12 weeks) besides the standard rat diet while the second group of elderly rats and adult rats (to 6-month- old adult-group) were only fed with the standard rat diet. The morphological analysis using light microscopy has shown marked myofibrillar losses, densely localized fibroblasts, vacuolizations, infiltrated cell accumulations, and collagen fibers in the myocardium of the elderly rats compared to the adults. We also detected a markedly increased amount of degenerated cardiomyocytes including the euchromatic nucleus. The MAHOC supplementation of the elderly rats provided marked ameliorations in these abnormal morphological changes in the heart tissue. Furthermore, electrophysiological analysis of electrocardiograms (ECGs) in the supplemented group showed significant attenuations in the prolonged durations of P-waves, QRS-complexes, QT-intervals, and low heart rates compared to the unsupplemented elderly group. The biochemical analysis also showed significant attenuations in the activity of arylesterase and total antioxidant status in the myocardium of the supplemented group. We further determined significant attenuations in the activity of a mitochondrial enzyme succinate dehydrogenase, known as a source of reactive oxygen species (ROS), and the decreased level of ATP/ADP in the heart homogenates of the supplemented group. Moreover, under in vitro conditions by using an aging-mimicked cardiac cell line induced by D-galactose, we demonstrated that MAHOC treatment could provide prevention of depolarization in mitochondria membrane potential and high-level ROS production. Overall, our data presented significant myocardial ameliorations in physiological aging-associated morphological alterations parallel to the function and biochemical attenuations with MAHOC supplementation, at most, through recoveries in mitochondria.

La suplementación con extracto de corteza de magnolia tiene un papel antioxidante en los mamíferos, sin embargo, su rol en la insuficiencia cardíaca asociada al envejecimiento fisiológico aún no se conoce. Por lo anterior, investigamos los efectos de un complejo de corteza de magnolia, incluidos los componentes magnolol y honokiol (MAHOC), en corazones de ratas seniles (grupo de edad de 24 meses). La alimentación de grupo de ratas seniles se complementó con MAHOC (400 mg/kg/d, durante 12 semanas) además de la dieta estándar, mientras que el segundo grupo de ratas seniles y ratas adultas (hasta el grupo de adultos de 6 meses) solo recibió la dieta estándar para ratas. El análisis morfológico mediante microscopía óptica ha mostrado marcadas pérdidas miofibrilares, fibroblastos densamente localizados, vacuolizaciones, acumulaciones de células infiltradas y fibras de colágeno en el miocardio de las ratas seniles en comparación con las adultas. También detectamos una cantidad notablemente mayor de cardiomiocitos degradados, incluido el núcleo eucromático. La suplementación con MAHOC de las ratas seniles proporcionó mejoras marcadas en estos cambios morfológicos anormales en el tejido cardiaco. Por otra parte, el análisis de los electrocardiogramas (ECG) en el grupo suplementado mostró atenuaciones significativas en las duraciones prolongadas de las ondas P, los complejos QRS, los intervalos QT y las frecuencias cardíacas bajas, en comparación con el grupo de ratas seniles sin suplementación alimenticia. El análisis bioquímico también mostró atenuaciones significativas en la actividad de la arilesterasa y el estado antioxidante total en el miocardio del grupo suplementado. Determinamos además atenuaciones significativas en la actividad de la enzima mitocondrial succinato deshidrogenasa, conocida como fuente de especies reactivas de oxígeno (ROS), y la disminución del nivel de ATP/ADP en los homogeneizados de corazón del grupo suplementado. Además, en condiciones in vitro mediante el uso de una línea de células cardíacas, imitando el envejecimiento inducido por D- galactosa, demostramos que el tratamiento con MAHOC podría prevenir la despolarización en el potencial de membrana de las mitocondrias y la producción de ROS de alto nivel. En general, nuestros datos presentaron mejoras miocárdicas significativas en alteraciones morfológicas asociadas con el envejecimiento fisiológico paralelas a la función y atenuaciones bioquímicas con la suplementación con MAHOC, como máximo, a través de recuperaciones en las mitocondrias.

Investigation of polysaccharide extracts from Iranian and French strains of Agaricus subrufescens against enzymes involved in Alzheimer's disease / Investigación de extractos de polisacáridos de cepas iraníes y francesas de Agaricus subrufescens contra enzimas relevantes para la enfermedad de Alzheimer

In this work, the inhibitory activity of a wide range of polysaccharide extracts from two Iranian and French strains of Agaricus subrufescens were evaluated toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Among them, two extracts S9 and S'7 obtained from Iranian and French strains under different extraction conditions showed selective AChE inhibitory activity with IC50 values of 154.63 and 145.43 µg/mL, respectively. It should be noted that all extracts from both strains demonstrated no BChE inhibitory activity. S9 and S'7 were also tested for their effect on amyloid beta (Aß) aggregation, antioxidant activity, and neuroprotectivity. Their activity against Aß aggregation was comparable to that of donepezil as the reference drug but they induced moderate antioxidant activity by DPPH radical scavenging activity and negligible neuroprotectivity against Aß-induced damage.

En este trabajo, se evaluó la actividad inhibitoria de acetilcolinesterasa (AChE) y butirilcolinesterasa (BChE) para varios extractos de polisacáridos de dos cepas iraníes y francesas de Agaricus subrufescens. Los extractos más potentes mostraron valores de IC50 de 154,63 y 145 µg/ml para las cepas iraní (S9) y francesa (S'7), respectivamente, las cuales se obtuvieron de diferentes condiciones de extracción; sin embargo, todos los extractos no mostraron actividad inhibitoria de BChE. Además, S9 y S'7 se probaron para determinar su efecto sobre la agregación de beta-amiloide (Aß), así como su actividad antioxidante y neuroprotectora. Su actividad inhibitoria de la agregación de Aß fue comparable con donepezil, fármaco de referencia, pero indujeron una actividad antioxidante moderada, medida mediante la captación de radicales DPPH, y una neuroprotectora insignificante contra el daño inducido por Aß.

Antioxidant effect and chemical composition of Ananas comosus [L.] Merr. peels from Peruvian northern / Efecto antioxidante y composición química de las cascaras de Ananas comosus [L.] Merr. del norte peruano

Pineapple peels has several beneficial properties including antioxidant activity. We investigated the antioxidant effect of five different peels of pineapple lyophilized extracts, not adsorbed and adsorbed onto Amberlite. They were examined using total phenolic contents (TPC), antioxidant effect by 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging and ferric reducing antioxidant power (FRAP). In addition, we analyzed the chemical composition by HPLC-ESI-QTOF-MS/MS. The main constituents of pineapple peels were tentatively identified as quercetin glycosides and N,N'-diferuloylspermidine. We conclude that the antioxidant activity in pineapple peels from District of Poroto, Province of Trujillo, Region of La Libertad, can be associated with the presence of flavonoid and spermidines.

Las cáscaras de piña tienen varias propiedades beneficiosas, incluida la actividad antioxidante. Investigamos el efecto antioxidante de cinco exfoliaciones diferentes de extracto liofilizado de piña, no adsorbidas y adsorbidas en Amberlita. Se examinaron utilizando los contenidos fenólicos totales (TPC), el efecto antioxidante mediante la eliminación del radical 1,1-difenil-2-picril-hidrazilo (DPPH) y el poder férrico antioxidante reductor (FRAP). Además, analizamos la composición química por HPLC-ESI-QTOF-MS/MS. Los principales constituyentes de las cáscaras de piña se identificaron tentativamente como glucósidos de quercetina y N,N'- diferuloylspermidina. Concluimos que la actividad antioxidante en las cáscaras de piña del Distrito de Poroto, Provincia de Trujillo, Región de La Libertad, puede estar asociada con la presencia de flavonoides y espermidinas.

Un novedoso agente en el tratamiento de la insuficiencia cardiaca con función sistólica deprimida / A novel agent in the treatment of heart failure with depressed systolic function

Resumen Introducción: Se revisará la evolución del tratamiento farmacológico de la insuficiencia cardiaca (IC) en los últimos 25 an˜os, desde el concepto de tratamiento con vasodilatadores, pasando por el bloqueo o inhibición del sistema renina-angiotensina-aldosterona y la inhibición betaadrenérgica y su importante contribución en la disminución de la morbimortalidad por IC, el papel de los péptidos natriuréticos y, finalmente, se conocerá uno de los estudios más importantes en el área cardiológica y específicamente en el manejo de la IC, en el cual se demuestra un enfoque modulador de los sistemas neuro humorales que se activan en estos pacientes. Objetivos: La IC constituye la etapa final de la mayoría de las enfermedades cardiovasculares, con una alta tasa de hospitalización y de morbimortalidad cardiovascular, siendo, por lo tanto, de interés constante la necesidad de encontrar un agente terapéutico innovador que disminuya significativamente estas complicaciones y también que mejore la calidad de vida de los que la presentan. Metodología: Se realizará una descripción del PARADIGM-HF Clinical Trial, que utilizó un compuesto sacubitrilo/valsartán para el manejo de la IC con un mecanismo modulador diferente del concepto de bloqueador de sistemas deletéreos que se activan cuando un paciente presenta síntomas y signos de IC. Conclusiones: La muerte por causas cardiovasculares u hospitalización por IC (el punto final primario) se produjo en 914 pacientes (21.8%) en el grupo sacubitrilo/valsartán y 1,117 pacientes (26.5%) en el grupo de enalapril (razón de riesgo en el grupo sacubitrilo/valsartán, 0.80; intervalo de confianza (IC) del 95%: 0.73 a 0.87; p < 0.001 (exacta p = 4.0 × 10 - 7)). De los pacientes que recibieron sacubitrilo/valsartán, 537 (12.8%) fueron hospitalizados por IC, en comparación con los 658 pacientes (15.6%) que recibieron enalapril (razón de riesgo, 0.79; IC del 95%, 0.71 a 0.89; p < 0.001). Un total de 711 pacientes (17.0%) en el grupo sacubitrilo/valsartán y 835 pacientes (19.8%) en el grupo de enalapril murió (razón de riesgo de muerte por cualquier causa, 0.84; IC del 95%, 0.76 a la 0.93; p < 0.001).

Abstract Introduction: A review is presented on the evolution of the pharmacological treatment of heart failure (HF) in the last 25 years, from the concept of treatment with vasodilators to the blocking or inhibition of the renin angiotensin aldosterone system. Beta-adrenergic inhibition and its important contribution in the reduction of morbidity and mortality due to HF will be discussed along with the role of the natriuretic peptides. One of the most important studies in the cardiology area, and specifically in the management of HF, is presented, in which an approach is demonstrated of the modulator of the neurohumoral systems that are activated in these patients. Objectives: HF is the final stage of most cardiovascular diseases, and has a high rate of hospital admission, as well as cardiovascular morbidity and mortality. Therefore, there is constant interest in the need to find an innovative therapeutic agent that significantly reduces these complications and that improves the quality of life of those who suffer from it. Methods: A description will be presented of the PARADIGM-HF Clinical Trial using a sacubitril/valsartán compound for the management of HF with a modulating mechanism different from the concept of a deleterious system blocker that is activated when a patient has symptoms and signs of heart failure. Conclusions: Death due to cardiovascular causes, or hospital admission due to heart failure (the primary endpoint) occurred in 914 patients (21.8%) in the Sacubitril / valsartán group, and 1117 patients (26.5%) in the enalapril group (risk ratio in the sacubitril / valsartán group, 0.80, with a 95% confidence interval [CI]: 0.73 to 0.87, P<0.001 ;exact P= 4.0 × 10 --7;). Of the patients receiving sacubitril / valsartán, 537 (12.8%) were hospitalised due to heart failure, compared with 658 patients (15.6%) receiving enalapril (hazard ratio 0.79, 95% CI: 0.71 to 0.89, P<.001). A total of 711 patients (17.0%) in the sacubitril / valsartán group, and 835 patients (19.8%) in the enalapril group, died (all-cause death rate, 0.84, 95% CI: 0.76 to 0.93, P<.001)

Chemical composition, in vitro cytotoxic and antioxidant activities of the essential oil of Peruvian Minthostachys mollis Griseb / Composición química, actividades citotóxicas y antioxidantes in vitro del aceite esencial de Minthostachys mollis Griseb peruano

The composition of the essential oil obtained by hydrodistillation from Minthostachys mollis Griseb (Lamiaceae) aerial parts was determined by GC and GC/MS. Menthone (13.2%), pulegone (12.4%), cis-dihydrocarvone (9.8%) and carvacrol acetate (8.8%) were the main essential oil components. The cytotoxic activity of the essential oil was in vitro measured using the MTT colorimetric assay. IC50 values were calculated on healthy non-tumor cells (HEK-293) and three human cancer cell lines (T24, DU-145 and MCF-7). In such latter cells, the estimated values were around 0.2 mg/mL. In addition, the antioxidant activity was determined by interaction with the stable free radical 2,2"-diphenyl-1-picrylhydrazyl. The essential oil was almost devoid of antioxidant activity indicating that its anti-proliferative action relies on other unknown mechanism.

La composición del aceite esencial obtenido por hidrodestilación a partir de partes aéreas de Minthostachys mollis Griseb (Lamiaceae) se determinó mediante GC y GC/MS. Mentona (13.2%), pulegona (12.4%), junto con cis-dihidrocarvona (9.8%) y acetato de carvacrol (8.8%) fueron los principales componentes del aceite esencial. La actividad citotóxica del aceite esencial se midió in vitro utilizando el ensayo colorimétrico MTT tanto en células sanas no tumorales (HEK-293) como en tres líneas celulares de cáncer humano (T24, DU-145 y MCF-7). Los valores de IC50 calculados fueron de alrededor de 0.2 mg/mL. Además, se determinó la actividad antioxidante por su interacción con el radical libre 2,2"-difenil-1-picrilhidrazilo. El aceite esencial tiene baja actividad antioxidante, lo que indica que su acción antiproliferativa depende de otro mecanismo desconocido.

Assessment of the antibacterial, cytotoxic and antioxidant activities of Morus nigra L. (Moraceae) / Avaliação das atividades antibacteriana, citotóxica e antioxidante de Morus nigra L. (Moraceae)

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.

Chemical composition, antimicrobial and antioxidant potential of the essential oil of Guarea kunthiana A. Juss / Composição química, potencial antimicrobiano e antioxidante do óleo essencial de Guarea kunthiana A. Juss

Abstract The essential oils are extracted from plant compounds and can present activities antimicrobial and antioxidant properties. The goals of the present study were: (a) to determine the chemical composition of the essential oil of Guarea kunthiana A. Juss using the method of gas chromatography coupled to mass spectrometry (GC-MS); (b) to evaluate the antimicrobial potential of this oil using the broth microdilution method against different microorganisms: five Gram-negative bacteria, four Gram-positive bacteria and a yeast and (c) to determine the antioxidant activity of the oil using the DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical assay. The GC-MS analyses allowed identifying 13 constituents, representing 96.52% of the essencial oil composition. The main compounds identified were α-zingiberene (34.48%), β-sesquiphellandrene (22.90%), and α-curcumene (16.17%). With respect to the antimicrobial activity, the essential oil was effective against all the microorganisms tested, except for the bacteria E. coli and K. pneumoniae, which were resistant to the action of the oil. From a general point of view, Gram-positive bacteria were more susceptible to the action of the essential oil than Gram-negative bacteria. The essential oil exhibited antioxidant potential.

Resumo Os óleos essenciais são compostos extraídos de plantas e podem apresentar propriedades antimicrobianas e antioxidantes. O objetivo deste trabalho foi (a) determinar a composição química do óleo essencial de Guarea kunthiana A. Juss pelo método de cromatografia gasosa acoplada à espectrometria de massas (CG-EM); (b) avaliar o potencial antimicrobiano deste óleo pelo método de microdiluição em caldo frente a diferentes micro-organismos, sendo cinco bactérias Gram-negativas, quatro Gram-positivas uma levedura e (c) por fim, determinar a atividade antioxidante do óleo pelo método de captura do radical livre 2,2-difenil-1-picril hidrazil (DPPH). As análises de CG-EM resultaram na identificação de 13 constituintes, representando 96,52% da composição do óleo essencial. Os principais compostos identificados foram α-Zingibereno (34,48%), β-Sesquifelandreno (22,90%) e α-Curcumeno (16,17%). Em relação à atividade antimicrobiana, o óleo essencial foi efetivo frente a todos os micro-organismos testados exceto para as bactérias E. coli e K. pneumoniae, as quais se apresentaram resistentes à ação do óleo. Em geral, as bactérias Gram-positivas foram mais suscetíveis à ação do óleo essencial em relação às Gram-negativas. O óleo essencial apresentou potencial.

Light curing resin cements containing iodonium salts promote suitable apical bonding of posts to radicular dentin

Abstract The aim of this study was to analyze the efficiency of experimental light-curing resin cements (ERCs) with a ternary photo-initiator system containing diphenyliodonium hexafluorphosphate (DPI) and different amines on retention of glass-fiber posts to dentin (GFP). ERCs formulations: a 1:1 mass ratio of 2,2-bis[4-(2-hydroxy-3-methacryloxypropoxy)phenylpropane and triethyleneglycol dimethacrylate. Camphorquinone was used as initiator. Six experimental groups were established according to the amine used: [ethyl-4-(dimethylamino)benzoate-EDMAB or 2-(dimethylamino)ethyl methacrylate-DMAEMA] and the concentration of DPI (0, 0.5 mol%, 1 mol%). The resin cements Variolink II (dual- and light-cured versions) were used as commercial reference. Eighty recently extracted bovine incisors (n = 10) were selected for this study. The roots were prepared and the fiber posts were cemented with the resin cement specified for each experimental group. Specimens from coronal, middle, and apical thirds of the root were subjected to push-out bond strength test 24 hours after bonding. Data were subjected to split-plot ANOVA and the Tukey test (p = 0.05). ERCs containing DPI showed statistically significant higher bond strengths compared with ERCs without DPI. ERCs containing DPI were statistically similar to VARIOLINK II - dual-cured and superior to VARIOLINK II - light-cured (except for EDMAB - 1DPI in the medium third and DMAEMA - 1DPI in the coronal third). Different amines did not influence post retention. The apical root region showed the lowest bond strength for the groups EDAB-0DPI, DMAEMA-0DPI and VARIOLINK II light-cured. Light-cured ERCs containing DPI were efficient for GFP retention to radicular dentin, with similar behaviour to that of dual-curing commercial resin cement.

Avaliação do efeito antiproliferativo da apocinina e diapocinina em células de osteossarcoma humano / Evaluation of the antiproliferative effect of apocynin and diapocynin on human osteosarcoma cells

O osteossarcoma (OS) é o tumor maligno primário mais comum do tecido ósseo, caracterizado pela formação de osteócitos anormais. Apesar do avanço nas terapias convencionais (quimioterapia e retirada do tumor), essas não conseguem eliminar totalmente as células tumorais e impedir a progressão da doença. Recentemente, agentes derivados de fontes naturais ganharam considerável atenção por causa de sua segurança, eficácia e disponibilidade imediata. Nesse sentido, a apocinina, inibidor do complexo NADPH-oxidase, vem sendo estudada como agente antitumoral em alguns tipos de câncer como: pâncreas, próstata, pulmão e mama. Apocinina é um pró-fármaco e sua ação parece estar relacionada à sua conversão produzindo a diapocinina, a qual se mostrou mais efetiva do que a apocinina. Portanto, o objetivo desse estudo é avaliar, in vitro, o potencial antitumoral da apocinina e diapocinina em células de osteossarcoma humano. Para isso, foram utilizados osteoblastos humanos normais (HOb) e osteossarcoma humano imortalizadas (SaOS-2) tratados ou não com apocinina e diapocinina em diversas concentrações. Foram realizados os ensaios de viabilidade celular, alterações morfológicas, apoptose celular, produção de espécies reativas de oxigênio (EROs), formação de colônias, migração, invasão e expressão do fator indutor de hipóxia-1alfa (HIF-1). Também foram conduzidos ensaios para verificar a atividade de metaloproteinase de matriz (MMP) 2 e 9. Os resultados em SaOS-2 mostraram que o tratamento com apocinina nas concentrações de 1,5 e 3 mM; e diapocinina nas concentrações de 0,75 e 1,5 mM reduziram a viabilidade; aumentaram o número de células em apoptose e diminuíram a produção de EROs; sem causar danos às células HOb. Além disso, essas mesmas concentrações inibiram a migração e invasão celular; diminuíram a expressão de HIF-1; e reduziram a atividade de MMP-2 em SaOS-2. Considerando os resultados obtidos, concluímos que a apocinina e diapocinina podem atuar como possíveis moduladores de células tumorais, sendo que a diapocinina mostrou ser mais efetiva nos parâmetros testados.(AU)

Osteosarcoma (OS) is the most common primary malignant tumor of bone tissue, characterized by the formation of abnormal osteocytes. Despite advances in conventional therapies (chemotherapy and surgery) they cannot completely eliminate tumor cells and prevent the progression of the disease. Recently, agents derived from natural sources have achieved considerable attention because of their safety, efficacy and immediate availability of therapies. In this way, apocynin, an inhibitor of the NADPH-oxidase complex, has been studied as an antitumor agent in some types of cancer, such as pancreas, prostate, lung and breast. Apocynin is a prodrug and its action indicate to be related to its conversion to diapocynin, which has been shown to be more efficient than apocynin itself. Thus, the aim of this study is to evaluate, in vitro, the antitumor potential of apocynin and diapocynin in human osteosarcoma cells. For this, normal human osteoblasts (HOb) and immortalized human osteosarcoma cells (SaOS-2) were treated or no-treated with apocynin and diapocynin in various concentrations. Cell viability assay, morphological alterations, cellular apoptosis, reactive oxygen species (ROS) production, colony formation, migration, invasion and expression of hypoxia-inducible factor-1 alpha (HIF-1) were performed. We also performed assays to verify the activity of matrix metalloproteinase (MMP) 2 and 9. The results in SaOS-2 showed that treatment with apocynin at concentrations of 1,5 e 3 mM; and diapocynin at concentrations of 0,75 e 1,5 mM reduced cell viability; increased the number of cells in apoptosis and decreased the production of ROS; without damaging HOb cells. Moreover, these same concentrations inhibited cell migration and invasion; decreased HIF-1 expression; and reduced MMP 2 activity in SaOS-2. Considering the results, we suggest that apocynin and diapocynin may act as possible modulators of tumor cells, and diapocynin has been shown to be more effective.(AU)

Safety and efficacy of fimasartan in Mexican patients with grade 1-2 essential hypertension / Seguridad y eficacia de fimasartán en pacientes mexicanos con hipertensión esencial de grados 1-2

Abstract: Objective: To evaluate efficacy and safety of 60 mg and 120 mg Fimasartan (FMS) alone or combined with 12.5 mg hydrochlorothiazide (HCTZ) in a Mexican population. Methods: A six month, treat-to-target, open study was conducted on subjects with grade 1-2 hypertension. The subjects were initially treated with 60 mg FMS once daily. In week 8, those with Diastolic Blood Pressure (DBP) <90 mmHg continued on the same FMS dose during the rest of the study, while those with DBP ≥90 mmHg were randomised to either 120 mg FMS or 60 mg FMS + 12.5 mg HCTZ once daily. In week 12, randomised subjects with DBP ≥90 mmHg received 120 mg FMS + 12.5 mg HCTZ, while those achieving target continued with their assigned treatment until the end of the study. Results: FMS 60 mg (n = 272) decreased both DBP and Systolic Blood Pressure (SBP) by 11.3 ± 8.9 (p<.0001) and 16.0 ± 14.1 (p<.0001) mmHg, respectively, with 75.4% of subjects reaching the treatment target. Subjects assigned to FMS 120 mg, FMS 60 mg + HCTZ 12.5 mg, or FMS 120 mg + HCTZ 12.5 mg once daily, showed significant reductions in DBP and SBP with their assigned treatment. At the end of the study, 237/272 subjects (87.1%) achieved a DBP < 90 mmHg and an SBP<140 mmHg. The most frequently reported adverse reactions included headache (3.7%), dry mouth (1.1%), transient liver enzyme increase (1.1%), and dizziness (0.7%). Conclusion: Fimasartan is safe and effective in Mexican subjects with grade 1-2 essential hypertension.

Resumen: Objetivo: Evaluar la eficacia y la seguridad de 60 y 120 mg de fimasartán (FMS) solo o combinado con 12.5 mg de hidroclorotiazida (HCTZ) en población mexicana. Métodos: Estudio abierto, de 24 semanas, con tratamiento escalado hasta el objetivo terapéutico en sujetos hipertensos grados 1-2. Tratamiento inicial: FMS 60 mg una vez al día; en la semana 8, los sujetos con presión arterial diastólica (PAD) <90 mmHg mantuvieron su tratamiento inicial durante el estudio, mientras que los sujetos con PAD ≥90 mmHg fueron aleatorizados a 120 mg de FMS o a 60 mg de FMS + 12.5 mg de HCTZ. En la semana 12, los sujetos aleatorizados con PAD ≥90 mmHg recibieron 120 mg de FMS + 12.5 mg de HCTZ; quienes alcanzaron el objetivo terapéutico mantuvieron su tratamiento asignado hasta finalizar el estudio. Resultados: FMS 60 mg (n = 272) disminuyó la PAD y la presión arterial sistólica (PAS) en 11.3 ± 8.9 (p < 0.0001) y 16.0 ± 14.1 (p < 0.0001) mmHg, respectivamente, con logro del objetivo de tratamiento en el 75.4% de los sujetos. Los sujetos asignados a 120 mg de FMS, a 60 mg de FMS + 12.5 mg de HCTZ 12.5 y a 120 mg de FMS + 12.5 mg de HCTZ mostraron reducciones significativas de PAD y PAS; al final del estudio, 237/272 sujetos (87.1%) lograron PAD <90 y PAS <140 mmHg. Las reacciones adversas más frecuentemente reportadas fueron: cefalea (3.7%), boca seca (1.1%), incremento de enzimas hepáticas (1.1%) y mareo (0.7%). Conclusión: FMS es seguro y eficaz en sujetos mexicanos con hipertensión esencial de grados 1-2.

Antifungal and antioxidant activity of fatty acid methyl esters from vegetable oils

ABSTRACT Fatty acid methyl esters (FAMEs) were obtained from vegetable oils of soybean, corn and sunflower. The current study was focused on evaluating the antifungal activity of FAMEs mainly against Paracoccidioides spp., as well as testing the interaction of these compounds with commercial antifungal drugs and also their antioxidant potential. FAMEs presented small IC50 values (1.86-9.42 μg/mL). All three FAMEs tested showed antifungal activity against isolates of Paracoccidioides spp. with MIC values ranging from 15.6-500 µg/mL. Sunflower FAMEs exhibited antifungal activity that extended also to other genera, with an MIC of 15.6 μg/mL against Candida glabrata and C. krusei and 31.2 μg/mL against C. parapsilosis. FAMEs exhibited a synergetic effect with itraconazole. The antifungal activity of the FAMEs against isolates of Paracoccidioides spp. is likely due to the presence of methyl linoleate, the major compound present in all three FAMEs. The results obtained indicate the potential of FAMEs as sources for antifungal and antioxidant activity.

Antiproliferative activity in tumor cell lines, antioxidant capacity and total phenolic, flavonoid and tannin contents of Myrciaria floribunda

ABSTRACT Myrciaria floribunda (H. West ex Willd.) O. Berg, Myrtaceae, is a native plant species of the Atlantic Rain Forest, from north to south of Brazil. The lyophilized ethyl acetate extract from the leaves of M. floribunda was investigated for its antiproliferative activity in tumor cell lines, antioxidant capacity and its total phenolic, flavonoid and tannin contents. Antiproliferative activity was tested in vitro against seven human cancer cells and against immortalized human skin keratinocytes line (HaCat, no cancer cell). Antioxidant activity was determined using 1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and oxygen radical absorbing capacity (ORAC) assays and total phenolic, flavonoid and tannin contents were determined by spectrophotometric techniques. Ethyl acetate extract of M. floribunda exhibited antiproliferative activity against cancer cell lines with total growth inhibition (TGI) between 69.70 and 172.10 µg/mL. For HaCat cell, TGI value was 213.60 µg/mL. M. floribunda showed a strong antioxidant potential: EC50 of 45.89±0.42 µg/mL and 0.55±0.05 mmol TE/g for DPPH and ORAC, respectively. Total phenolic content was 0.23±0.013g gallic acid equivalents (GAE)/g extract and exhibited 13.10±1.60% of tannins content. The content of flavonoid was 24.08±0.44% expressed as rutin equivalents. These results provide a direction for further researches about the antitumoral potential of M. floribunda.

Interaction between ascorbic acid and gallic acid in a model of fructose-mediated protein glycation and oxidation

Background: Dietary plant-based foods contain combinations of various bioactive compounds such as phytochemical compounds and vitamins. The combined effect of these vitamins and phytochemicals remains unknown, especially in the prevention of diabetes and its complications. The present study aimed to investigate the combined effect of ascorbic acid and gallic acid on fructose-induced protein glycation and oxidation. Results: Ascorbic acid (15 µg/mL) and gallic acid (0.1 µg/mL) reduced fructose-induced formation of advanced glycation end products (AGEs) in bovine serum albumin (BSA; 10 mg/mL) by 15.06% and 37.83%, respectively. The combination of ascorbic acid and gallic acid demonstrated additive inhibition on the formation of AGEs after 2 weeks of incubation. In addition, synergistic inhibition on the formation of amyloid cross-ß structure and protein carbonyl content in fructose-glycated BSA was observed. At the same concentration, the combination of ascorbic acid and gallic acid produced a significant additive effect on the 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity. Conclusion: Combining natural compounds such as ascorbic acid and gallic acid seems to be a promising strategy to prevent the formation of AGEs.

In vitro antioxidant activity and qualitative phytochemical analysis of two Vismia (Hypericaceae) species collected in Los Andes, Venezuela / Actividad antioxidante in vitro y análisis fitoquímico cualitativo de dos especies de Vismia (Hypericaceae) recolectadas en Los Andes, Venezuela

Abstract:Vismia genus is distributed mainly in tropical and subtropical regions of Central, South America and some areas of Africa. According to previous investigations, antioxidant potential of Vismia species might be related to anthrones, anthraquinones, flavonoids and phenol derivatives biosynthesized by these plants. In this investigation, phytochemical screening of Vismia baccifera (VB) from Mérida-Venezuela and Vismia macrophylla (VM) from Táchira-Venezuela methanolic extracts, carried out using various chemical assays, revealed an abundant presence of anthraquinones in both species analyzed. Glycosides were also present while flavones and dehydroflavones were observed abundantly in VB but moderated in VM. Triterpenes were also detected and steroids showed to be abundant in VM but moderate in VB. On the other hand, antioxidant capacity measured by the DPPH assay showed that VM possesses a stronger antioxidant activity than VB with IC50 5.50 µg mL-1. Phenol and flavonoid assays carried out by Folin-Ciocalteu and colorimetric test also revealed that methanol extracts of both species contain high concentrations of these metabolites. A relationship between the antioxidant activity, total phenol and flavonoids content of the extracts analyzed was demonstrated in this investigation since those samples with higher phenolic concentrations showed likewise higher antioxidant activity. Rev. Biol. Trop. 64 (4): 1431-1439. Epub 2016 December 01.

Resumen:El género Vismia esta distribuido principalmente en las regiones tropicales y subtropicales de Centro, Sur América y algunas zonas de África. De acuerdo a reportes previos, el potencial antioxidante de las especies de Vismia puede estar relacionado con antronas, antraquinonas, flavonoides y derivados fenólicos biosintetizados por estas plantas. En la presente investigación, el tamizaje fitoquímico de los extractos metanólicos de Vismia baccifera (VB) de Mérida-Venezuela y Vismia macrophylla (VM) de Táchira-Venezuela realizado con diferentes ensayos químicos reveló abundante presencia de antraquinonas en ambas especies analizadas. Glucósidos también estuvieron presentes mientras que flavonas y dehidroflavonas fueron observados abundantemente en VB pero con presencia moderada en VM. Triterpenos y esteroides también fueron detectados mostrando ser abundantes en VM y moderados en VB. Por otro lado, la actividad antioxidante determinada por el método DPPH reveló que VM posee actividad antioxidante más fuerte que VB con un IC50 de 5.50 µg mL-1. El ensayo del contenido de fenoles y flavonoides realizado con los métodos de Folin-Ciocalteu y test colorimétrico también demostró que los extractos metanólicos de ambas especies contienen altas concentraciones de estos metabolitos. En este estudio se observó una relación entre la actividad antioxidante, el contenido de fenoles y de flavonoides en los extractos analizados ya que las muestras que presentaron concentraciones más altas de fenoles y flavonoides también mostraron una mayor actividad antioxidante.

Antioxidant activity and phenol content of extracts of bark, stems, and young and mature leaves from Blepharocalyx salicifolius (Kunth) O. Berg / Atividade antioxidante e teor de polifenóis de extratos de cascas (súber), caule, folhas jovens e folhas maduras de Blepharocalyx salicifolius (Kunth) O. Berg (Murta)

Abstract Phenolic compounds are a group of plant secondary metabolites known to have a variety of bioactivities, including the ability to function as antioxidants. Because of the side effects of the use of synthetic substances, the search for natural and less toxic compounds has increased significantly. This study was designed to evaluate the antioxidant activity and phenol content of hexane, ethyl acetate, and aqueous extracts of the bark (suber) and stems as well as the young and mature leaves of Blepharocalyx salicifolius. The extracts were obtained by extraction with organic solvents and subsequent fractionation by chromatographic partition coefficient. Preliminary tests for the presence of antioxidants were performed using bioautography in thin-layer chromatography. The antioxidant activity of the extracts was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and the phenol content of the extracts was quantified using the Folin-Ciocalteu technique. The results showed that 9 of the 12 extracts evaluated displayed very strong antioxidant activity and three displayed moderate activity. Aqueous extracts of the young leaves and bark and the ethyl acetate extract of the young leaves showed the highest levels of antioxidant activity and total phenolic content (TPC). A correlation was observed between TPC and antioxidant activity index (AAI) with a correlation coefficient (r2) of 0.7999. Thus, the high phenol content of B. salicifolius extracts and its correlation with antioxidant activity provide substrates for further studies.

Resumo Os polifenóis são um grupo de metabólitos secundários vegetais que possuem uma variedade de bioatividades conhecidas, dentre elas a capacidade de funcionar como antioxidantes. Devido aos efeitos colaterais do uso excessivo de substâncias sintéticas, a busca por compostos naturais e menos tóxicos têm aumentado significativamente. Esse estudo teve por objetivo avaliar a atividade antioxidante e o teor de polifenóis dos extratos hexânicos, acetato de etila e aquosos de cascas (súber), caules, folhas jovens e folhas maduras de Blepharocalyx salicifolius. Os extratos foram obtidos por meio de extração com solventes orgânicos e subsequente fracionamento em cromatografia por coeficiente de partição. Testes preliminares da presença de compostos com atividade antioxidante foram realizados por meio de bioautografia em cromatografia de camada delgada. Os extratos foram submetidos ao teste da capacidade sequestrante do radical 2,2-difenil-1-picrilhidrazil (DPPH) para quantificação da atividade antioxidante e submetidos ao teste com o reagente de Folin-Ciocalteu para quantificação dos polifenóis. Os resultados mostraram que dos 12 extratos avaliados, 9 apresentaram atividade antioxidante muito forte e 3 atividade moderada. Os extratos aquosos de folhas jovens e cascas e o extrato acetato de etila de folhas jovens apresentaram os maiores índices de atividade antioxidante e teor de polifenóis (TPC). A correlação entre TPC e o índice de atividade antioxidante (AAI) observada foi de r2 = 0,7999. Dessa forma, ficou evidenciado o elevado teor de polifenóis e sua correlação com a atividade antioxidante nos extratos de B. salicifolius, fornecendo subsídios para novos estudos.

In vitro studies reveal antiurolithic effect of Terminalia arjuna using quantitative morphological information from computerized microscopy

ABSTRACT Purpose: For most cases, urolithiasis is a condition where excessive oxalate is present in the urine. Many reports have documented free radical generation followed by hyperoxaluria as a consequence of which calcium oxalate (CaOx) deposition occurs in the kidney tissue. The present study is aimed to exam the antilithiatic potency of the aqueous extract (AE) of Terminalia arjuna (T. arjuna). Materials and Methods: The antilithiatic activity of Terminalia arjuna was investigated in vitro nucleation, aggregation and growth of the CaOx crystals as well as the morphology of CaOx crystals using the inbuilt software ‘Image-Pro Plus 7.0’ of Olympus upright microscope (BX53). Antioxidant activity of AE of Terminalia arjuna bark was also determined in vitro. Results: Terminalia arjuna extract exhibited a concentration dependent inhibition of nucleation and aggregation of CaOx crystals. The AE of Terminalia arjuna bark also inhibited the growth of CaOx crystals. At the same time, the AE also modified the morphology of CaOx crystals from hexagonal to spherical shape with increasing concentrations of AE and reduced the dimensions such as area, perimeter, length and width of CaOx crystals in a dose dependent manner. Also, the Terminalia arjuna AE scavenged the DPPH (2, 2-diphenyl-1-picrylhydrazyl) radicals with an IC50 at 13.1µg/mL. Conclusions: The study suggests that Terminalia arjuna bark has the potential to scavenge DPPH radicals and inhibit CaOx crystallization in vitro. In the light of these studies, Terminalia arjuna can be regarded as a promising candidate from natural plant sources of antilithiatic and antioxidant activity with high value.

Antioxidant capacity of several Iranian, wild and cultivated strains of the button mushroom

The white button mushroom, Agaricus bisporus, is the most commonly grown mushroom in Iran; however, there is a significant shortage of research on its antioxidant activity and other medicinal properties. The aim of this study was to evaluate antioxidant capacity of the methanolic extracts from four cultivated strains and four Internal Transcribed Spacer (ITS)-identified, Iranian wild isolates of A. bisporus. Evaluations were made for total phenols, flavonoids and anthocyanins, and 2, 2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. Overall, results showed that all the wild isolates exhibited significantly lower DPPH-derived EC₅₀, compared to the cultivated strains (p < 0.05). A relatively high relationship was observed between total phenols and flavonoids or anthocyanins (r² > 0.60). However, these constituents could not statistically differentiate the group of wild samples from the cultivated ones, and there was low correlation with the DPPH-derived EC₅₀s (r² < 0.40). In conclusion, comparisons showed that wild isolate 4 and cultivated strains A15 and H1 had higher antioxidant capacity than the others (p < 0.05). This result identifies these mushrooms as good candidates for further investigation.

Actividad antioxidante de extractos de diferente polaridad de Ageratum conyzoides L / Antioxidant activity of different polarity extracts from Ageratum conyzoides L

The present study aimed to investigate the antioxidant activity of extracts of different polarity of the species Ageratum conyzoides L., evaluating by different spectrophotometric methods: ABTS•+, DPPH•, FRAP and ORAC. Extracts of A. conyzoides L., showed good antioxidant activity in the methodologies evaluated. The extract was the most active of ethyl acetate (ACExtA) which showed the best evaluated values techniques with higher power as determined by the assay values of TEAC ORAC = 494048.95 +/- 29695.80 uMol Trolox/100g sample. Measurements of antioxidant activity by different techniques offer advantages in terms of predicting the in vitro antioxidant capacity of this plant, it is also recommended to explore the structural characteristics of the compounds present in the ethyl acetate extract of the plant with to explore the potential benefits and possible mechanisms of action of new antioxidants...

El presente trabajo tuvo como objetivo investigar la actividad antioxidante de extractos de diferente polaridad de la especie Ageratum conyzoides L., mediante la evaluación por diferentes métodos espectrofotométricos: ABTS•+, DPPH•, FRAP y ORAC. Los extractos de A. conyzoides L., presentaron una buena actividad antioxidante en las metodologías evaluadas. El extracto más activo fue el de acetato de etilo (ACExtA), que presentó los mejores valores por las técnicas evaluadas con la mayor potencia determinada por el ensayo ORAC con valores de TEAC = 494048,95 +/- 29695,80 uMol Trolox/100g muestra. Las mediciones de la actividad antioxidante por diferentes técnicas, ofrecen ventajas en términos de la predicción de la capacidad antioxidante in vitro de esta planta, además se recomienda explorar las características estructurales de los compuestos presentes en el extracto de acetato de etilo de esta planta con el fin de investigar los beneficios potenciales y los mecanismos de acción de posibles nuevos antioxidantes...