Mechanism of the vasodilator effect of mono-oxygenated xanthones: a structure-activity relationship study.

The present study characterized the mechanisms involved in the vasodilator effect of two mono-oxygenated xanthones, 4-hydroxyxanthone and 4-methoxyxanthone. 9-Xanthenone, the base structure of xanthones, was used for comparison. 4-Hydroxyxanthone and 9-xanthenone induced a concentration-dependent and endothelium-independent vasodilator effect in arteries precontracted with phenylephrine (0.1 µmol ·â€ŠL-1) or KCl (50 mmol ·â€ŠL-1). 4-Methoxyxanthone induced a concentration-dependent vasodilator effect in arteries precontracted with phenylephrine, which was partially endothelium-dependent, and involved production of nitric oxide. In endothelium-denuded arteries precontracted with KCl, the vasodilator effect of 4-methoxyxanthone was abolished. The vasodilator effect of 4-hydroxyxanthone (96.22 ± 2.10 %) and 4-methoxyxanthone (96.57 ± 12.40 %) was significantly higher than observed with 9-xanthenone (53.63 ± 8.31 %). The presence of an oxygenated radical in position 4 made 4-hydroxyxanthone (pIC50 = 4.45 ± 0.07) and 4-methoxyxanthone (pIC50 = 5.04 ± 0.09) more potent as a vasodilator than 9-xanthenone (pIC50 = 3.92 ± 0.16). In addition, 4-methoxyxanthone was more potent than the other two xanthones. Ca2+ transients in vascular smooth muscle cells elicited by high K+ were abolished by 4-hydroxyxanthone and 9-xanthenone. The endothelium-independent effect of 4-methoxyxanthone was abolished by inhibition of K+ channels by tetraethylammonium. The current work shows that an oxygenated group in position 4 is essential to achieve Emax and to increase the potency of xanthones as vasodilators. Substitution of an OH by OCH3 in position 4 increases the potency of the vasodilator effect and changes the underling mechanism of action from the blockade of L-type calcium channels to an increase in NO production and activation of K+ channels.

2,2',4-trihydroxybenzophenone: crystal structure, and anti-inflammatory and antioxidant activities.

The crystal structure of '2,2',4-trihydroxybenzophenone' (=(2,4-dihydroxyphenyl)(2-hydroxyphenyl)methanone; 1) was determined, and its molecular structure, along with intra- and intermolecular H-bonds, was analyzed. The anti-inflammatory potential of 1, evaluated by means of the rat-paw-edema assay, with carrageenan as inflammation stimulus, was found to be similar high as that of indomethacin. In contrast, benzophenone proper (2) was hardly active in this assay. Our results indicate that these anti-inflammatory effects are related to the action of kinins and prostaglandins. The radical-scavenging properties of 1 towards DPPH were found to be similar as those of typical phenolics, but somewhat lower than that of ascorbic acid. The structure-activity relationship (SAR) of 1 is discussed.

7-epiclusianone, the natural prenylated benzophenone, inhibits superoxide anions in the neutrophil respiratory burst.

Despite defenses by polymorphonuclear neutrophils in the host against invading agents, overproduction of oxidant species by phagocytes can lead to damage in the surrounding tissues. Several benzophenones have been shown to possess anti-inflammatory properties. The effect of the natural benzophenone 7-epiclusianone isolated from leaves of Garcinia brasiliensis was investigated by using in vitro antioxidant and ex vivo anti-inflammatory assays, focusing on the neutrophil respiratory burst and on the biochemical pathways involved. The bioactive extract, 7-epiclusianone, showed low in vitro antioxidant activity as evaluated by the 2,2-diphenyl-1-picrylhydrazyl free radical scavenging assay, the reducing power test, or the chelating power assay. However, the benzophenone displayed potent activity in the ex vivo model of the neutrophil respiratory burst, inhibiting the generation of superoxide anions in a dose-dependent manner. When the respiratory burst was triggered by N-formyl-methionyl-leucyl-phenylalanine, a chemotactic peptide, the 50% effective concentration (EC(50)) was 41.18 µg/10(7) cells. When phagocytes were stimulated directly through protein kinase C via phorbol, the EC(50) was 34.3 µg/10(6) cells. The results indicated that 7-epiclusianone was able to down-regulate inflammatory phagocyte superoxide anion release through a mechanism controlled by tyrosine protein phosphorylation and by a direct stimulation of protein kinase C. These findings could lead to new therapeutic approaches for inflammation management and the development of new drugs.

Experimental atherosclerosis in rabbits.

Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.

Vasodilator and antioxidant effect of xanthones isolated from Brazilian medicinal plants.

Vasorelaxant and antioxidant activities are important in the therapy for cardiovascular diseases. We aimed at investigating the vasorelaxant and antioxidant activities of six xanthones isolated from Brazilian medicinal plants. Xanthone ( 1), 1-hydroxyxanthone ( 2), 4-hydroxyxanthone ( 3), 1-hydroxy-8-methoxyxanthone ( 4), 1,3-dihydroxy-7-methoxyxanthone ( 5) and 2,6,8-trihydroxy-1-methoxyxanthone ( 6) induced concentration-dependent vasorelaxant effects in endothelium-intact mice aortic rings. The presence of a hydroxy group in position 1 seemed to decrease the vasodilator effect while a hydroxy in position 4 and an increased number of hydroxy groups improved the vasorelaxatory potential of xanthones. All xanthones showed antioxidant activity but their potencies did not correlate with the vasodilator effect. Our results suggest that the tested xanthones are potentially vasorelaxant and antioxidant compounds but the two activities are not interrelated.

Exercício físico e diabetes mellitus tipo 2 / Physical exercise and type 2 diabetes mellitus (exercise and diabetes)

Um estilo de vida sedentário deve ser considerado um importante fator de risco capaz de ser modificado para indivíduos com diabetes mellitus (DM) tipo 2, já que atividade física regular oferece múltiplos benefícios que incluem melhora da sensibilidade à insulina e do controle glicêmico, aumento do condicionamento cardiorespiratório e redução do risco de mortalidade cardiovascular. Entretanto, o estabelecimento de programas de treinamentos e de guias práticos para o manejo adequado na diabetes tipo 2 não têm sido sugeridos num consenso único. Dessa forma, o presente estudo selecionou publicações realizadas a partir de dados Pubmed, objetivando discutir informações que estão sendo descritas na literatura de forma a reforçar bases que representem uma resposta adaptativa às demandas do treinamento, apoiando uma positiva função da atividade física no cuidado da diabetes tipo 2.

A sedentary lifestyle should be considered an important modifiable risk factor for individuals with type 2 diabetes mellitus (DM) already that regular physical activity offers many benefits including improved insulin sensitivity and glycemic control, increased cardiorespiratory fitness and reduced risk of cardiovascular mortality. However, the establishment of training programs and practical guidelines for management of type 2 diabetes has not been suggested in a single consensus. Thus, this study through of the selection of publications was performed on Pubmed aims to discuss the data being reported in the literature in order to reinforce the base that represent an adaptative response to the demands of training, supporting a positive role of physical activity in the management of type 2 diabetes.

Mammeigin.

Single crystals of the phenylcoumarin named mammeigin (or mammea A/AA cycle D) [systematic name: 5-hydroxy-8,8-dimethyl-6-(3-methylbutanoyl)-4-phenyl-2H,8H-pyrano[2,3-f]chromen-2-one], C25H24O5, were obtained in the course of a chemotaxonomic study of the Guttiferae family. Mammeigin was extracted from the fruits of Kilmeyera pumila. The structure reveals an infinite three-dimensional network stabilized by non-classical intermolecular hydrogen bonds.

Flavonóides e aterosclerose / Flavonoids and atherosclerosis

Dentre as enfermidades pertencentes ao grupo das doenças cardiovasculares, a aterosclerose têm sido, atualmente, considerada problema de saúde pública no Brasil. tendo em vista o seu papel no perfil de mortalidade e das alterações tatológicas que acarretam. Pesquisas têm demonstrado associações entre o consumo de gordura saturada, nível de coleterol e doenças coronárias, no entanto, medidas dietéticas isoladas mostram-se, frqquentemente, insuficientes, tornando-se necessária à associação dessas com fármacos hipolipidêmicos capazes de reduzir a síntese endógena de colesterol ou melhorar a eficiência de sua remoção do plasma. Durante os últimos anos, um número crescente de estudos tem relacionado flavonóides a promissores fármacos naturais, uma vez que têm sido atribuidos a esses a capacidade de modificar a biossíntese de eicosanóides (resposta anti-prostanóide e antiinflamatória), proteger colesterol LDL da oxidação (inibindo formação de placa aterosclerótica), prevenir agregação plaquetária (efeitos anti-trombóticos) e promover relaxamento de músculo liso (efeito anti-hipertensivo e anti-isquêmico). Sendo assim, essa revisão sugere que a proteção contra doenças cardiovasculares associadas por meio de dietas ricas em flavonóides pode resultar em uma variedade de efeitos produzidos por diferentes mecanismos, necessitando, portanto, de maiores investigações e entendimewntos científicos.

Aterosclerose experimental em coelhos / Experimental atherosclerosis in rabbits

Numerosas pesquisas têm sido realizadas utilizando modelos experimentais para estudar o desenvolvimento da aterosclerose com dieta induzindo hiperlipidemia. Devido ao fato de que coelhos são muito sensíveis a dietas ricas em colesterol e acumulam grandes quantidades no plasma, a utilização destes animais como modelo experimental para avaliar o desenvolvimento de aterosclerose é de grande relevância, trazendo informação sobre fatores que contribuem para progressão e regressão aplicadas a situações humanas. Sendo assim, nessa revisão a função aterogênica do colesterol é mostrada em trabalhos que incluem o coelho como modelo experimental, uma vez que este animal tornou-se o mais popular modelo experimental de aterosclerose.

Many researches have been conducted in experimental models in order to study the development of atherosclerosis from hyperlipidemia-inducing diets. Since rabbits are very sensitive to cholesterol-rich diets and accumulate large amounts of cholesterol in their plasma, their use as experimental models to evaluate the development of atherosclerosis is highly relevant and brings information on factors that contribute to the progression and regression of this condition that can be applied to humans. As such, this review includes studies on the atherogenic function of cholesterol based on rabbits as the experimental model, since they have become the most largely used experimental model of atherosclerosis.

Efeitos antidiabéticos de plantas medicinais / Antidiabetic effects of the medicinal plants

Diabetes mellitus (DM) é uma doença metabólica crônica caracterizada por hipeglicemia que tem impacto significante em seus pacientes. Sua incidência está crescendo rapidamente conduzindo para aumento no custo dos cuidados da doença e de suas complicações. O tratamento envolve, além de controle dietético e atividade física, o uso de fármacos que ocasionam efeitos colaterais para atingir ações farmacológicas desejadas. Entretanto, produtos de plantas são, freqüentemente, considerados menos tóxicos e com menos efeitos colaterais que drogas sintéticas e amplamente utilizadas pela população. Nesse trabalho várias espécies de plantas utilizadas experimentalmente ou na medicina popular, agindo de diferentes formas de modo a controlar glicemia e/ou inibir sintomas e complicações características da diabetes serão revisadas para avaliação de seus supostos efeitos terapêuticos.

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemy that has a significant impact for their patients. Its incidence is raising leading to an increase in the cost of the cares of the disease and of its complications. The treatment involves, besides dietary control and physical activity, the use of drugs that cause side effects to reach wanted pharmacological actions. However, products of plants are, frequently, considered less poisonous and with fewer side effects than synthetic drugs and widely used by the population. In this paper, several species of plants, used experimentally or in the popular medicine, acting by different ways to control glycemia and/or to inhibit symptoms and characteristic complications of the diabetes, they will be reviewed for evaluation of their supposed therapeutic effects.

Efeito de flavonóides no metabolismo do ácido araquidônico / Effect of flavonoids on the arachidonic acid metabolism

Os produtos da açäo das enzimas ciclooxigenase e lipoxigenase sobre o ácido araquidônico säo prostaglandinas, tromboxanos e leucotrienos, também denominados eicosanóides. Tais compostos säo agentes homeostáticos, envolvidos na manutençäo da integridade dos sistemas inflamatório, cardiovascular e renal. Vários pesquisadores têm demonstrado que flavonóides apresentam inúmeras propriedades farmacológicas, entre elas atividade antiinflamatória e hipocolesterolêmica, reduzindo, assim, o risco de doenças cardiovasculares e um dos principais mecanismos de açäo propostos é a inibiçäo das enzimas, envolvidas no metabolismo final do araquidonato. Este trabalho mostra uma revisäo sobre o metabolismo do ácido araquidônico e os efeitos farmacológicos de flavonóides nessa rota metabólica