Effect of umbelliferone (7-hydroxycoumarin, 7-HOC) on the enzymatic, edematogenic and necrotic activities of secretory phospholipase A2 (sPLA2) isolated from Crotalus durissus collilineatus venom

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Avaliação in vitro e in vivo da Atividade Antioxidante do Extrato Hidroetanólico de Folhas de Turnera ulmifolia Linn. var. elegans (Turneraceae)

Recently, it has been a increasing interest in the antioxidative role of natural products to aid the endogenous protective biological systems against the deleterious effects of oxygen (ROS) and nitrogen (RNS) reactive species. Many antioxidant compounds, naturally occurring from plant sources. Natural antioxidants can protect and prevent the human body from oxidative stress and retard the progress of many diseases in which free radical are involved. Several plants used in the folk medicine to treat certain disorders that are accompanied by inflammation and other pharmacological properties have been proved their attributed properties, such antioxidant activity. Turnera ulmifolia Linn. var. elegans (Turneraceae), frequently employed by population as a medicinal plant, demonstrated antioxidant activity by in vitro and in vivo assays, using its leaf hydroethanolic extract (10%) he in vitro DPPH radical-scanvenging activity showed a strong antioxidant activity (86.57% ± 0.14), similar to Carduus marianus and catequine effects. For the in vivo assays, adult female Wistar rats (n=48) with carbon tetrachloride hepatic injury induced (2,5mL/kg i.p.) were used, Six groups or rats were uses (n=8) [G1 = control (1,25 mL/kg i.p. vehicle); G2 = CCl4 (2,5 mL/kg i.p.); G3 = CCl4 + extract 7 days (500 mg/kg p.o.); G4 = CCl4 + Legalon® 7 days (50 mg/kg p.o.), G5 = CCl4 + extract 21 days (500 mg/kg p.o.) e G6 = CCl4 + Legalon® 21 days (50 mg/kg p.o.)]. The hepatic oxidative injury was evaluated through biochemical parameters [alanine amino transferase (ALT), aspartate amino transferase (AST)] histopathological study, while thiobarbituric acid reactive products (TBAR), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were used to evaluate proantioxidant parameters. The plant extract tested was found effective as hepatoprotective as evidenced by a decreasing in the ALT and AST activities (p<0.001) and TBAR (plasma, p<0.001 and liver, p<0.001). Levels of GSH (blood, p<0.001 and liver, p<0.001) and antioxidant enzymes [CAT erythrocyte (p<0.05) and hepatic (p<0.01); SOD erythrocyte (p<0.001) and hepatic (p<0.001); GPx erythrocyte (p<0.001) and hepatic (p<0.001)] were also significantly increased. Histopathological changes induced by CCl4 were significantly reduced by the extract treatment. The data obtained were comparable to that of Legalon®, a reference hepatoprotective drug. The results showed that T. ulmifolia leaf extract protects against CCl4 induced oxidative damage. Therefore, this effect must be associated to its antioxidant activity, attributed to the phenolic compounds, present in these extract, which can act as free radical scavengers

Encoding mechanisms based on fast oscillations in the retina of the cat and their dependencies on anesthesia

Processing in the visual system starts in the retina. Its complex network of cells with different properties enables for parallel encoding and transmission of visual information to the lateral geniculate nucleus (LGN) and to the cortex. In the retina, it has been shown that responses are often accompanied by fast synchronous oscillations (30 - 90 Hz) in a stimulus-dependent manner. Studies in the frog, rabbit, cat and monkey, have shown strong oscillatory responses to large stimuli which probably encode global stimulus properties, such as size and continuity (Neuenschwander and Singer, 1996; Ishikane et al., 2005). Moreover, simultaneous recordings from different levels in the visual system have demonstrated that the oscillatory patterning of retinal ganglion cell responses are transmitted to the cortex via the LGN (Castelo-Branco et al., 1998). Overall these results suggest that feedforward synchronous oscillations contribute to visual encoding. In the present study on the LGN of the anesthetized cat, we further investigate the role of retinal oscillations in visual processing by applying complex stimuli, such as natural visual scenes, light spots of varying size and contrast, and flickering checkerboards. This is a necessary step for understanding encoding mechanisms in more naturalistic conditions, as currently most data on retinal oscillations have been limited to simple, flashed and stationary stimuli. Correlation analysis of spiking responses confirmed previous results showing that oscillatory responses in the retina (observed here from the LGN responses) largely depend on the size and stationarity of the stimulus. For natural scenes (gray-level and binary movies) oscillations appeared only for brief moments probably when receptive fields were dominated by large continuous, flat-contrast surfaces. Moreover, oscillatory responses to a circle stimulus could be broken with an annular mask indicating that synchronization arises from relatively local interactions among populations of activated cells in the retina. A surprising finding in this study was that retinal oscillations are highly dependent on halothane anesthesia levels. In the absence of halothane, oscillatory activity vanished independent of the characteristics of the stimuli. The same results were obtained for isoflurane, which has similar pharmacological properties. These new and unexpected findings question whether feedfoward oscillations in the early visual system are simply due to an imbalance between excitation and inhibition in the retinal networks generated by the halogenated anesthetics. Further studies in awake behaving animals are necessary to extend these conclusions

Medicina caseira em sete localidades da região de Bauru, SP

Este trabalho foi realizado nas localidades de Duartina, Piratininga, Presidente Alves, Bocaina, Boracéia, Dois Córregos e Potunduva (Região de Bauru), em 1981. O objetivo foi avaliar o conhecimento e o uso de plantas medicinais, pela população. Foram entrevistadas 372 pessoas, das quais, a maioria pertencia ao estrato social baixo. Mais de 95% das pessoas conheciam plantas medicinais, com grande utilização de duas a quatro variedades. O não-uso representou, no total, apenas 10,8%. O local de obtenção mais freqüente foi quintal, seguindo-se a farmácia. Citaram-se 118 plantas diferentes para uso medicinal Destas, em apenas 9,3% não se encontrou, na literatura, o nome científico correspondente e, em 17,0%, a indicação do valor medicinal O uso mencionado pelos entrevistados foi coincidente com os da literatura em quase 70% das vezes, em pelo menos um sintoma ou doença. Discutiram-se as razões do recente incremento da medicina caseira; alguns aspectos referentes à industrialização e comercialização de plantas medicinais e sublinhou-se a necessidade de promoção de pesquisas farmacológicas para o melhor conhecimento do valor terapêutico da flora medicinal brasileira.

Propolis effect on streptozotocin-induced diabetic rats

Propolis is one of the hive products that has been used extensively in folk medicine, due to its several biological and pharmacological properties. Besides, propolis-containing products have been intensely marketed by the pharmaceutical industry and health-food stores. This work was carried out in order to investigate whether propolis treatment could revert the metabolic alterations of streptozotocin-induced diabetic rats. Animals were kept in metabolic cages and diabetes was induced by a single dose of streptozotocin (35 mg/kg, IV). After a week, rats with glycemia higher than 230 mg/dL were divided into two groups and treated with ethanolic extract of propolis (10 and 90 mg/kg, PO) for seven days. Glycemia and free fatty acids were determined, as well as food and water intake, body weight and urine volume were registered weekly. Data showed no significant differences in the analyzed variables. Based on these results, one may conclude that propolis had no effects after diabetes establishment, in our conditions assays. Further assays with different concentrations of propolis and periods of administration should be carried out in order to evaluate its therapeutic potential in this disease.

Propolis: Is there a potential for the development of new drugs?

Introduction: Propolis has plenty of biological and pharmacological properties and its mechanisms of action have been widely investigated in the last years, using different experimental models in vitro and in vivo. Researchers have been interested in the investigation of isolated compounds responsible for propolis action; however, there is lack of clinical research on the effects of propolis.Strategy and objectives: Since propolis-containing products have been marketed and humans have used propolis for different purposes, the goal of this review is to discuss the potential of propolis for the development of new drugs, by comparing data from the literature that suggest candidate areas for the establishment of drugs against tumors, infections, allergy, diabetes, ulcers and with immunomodulatory action.Conclusions: The efficacy of propolis in different protocols in vitro and in vivo suggests its therapeutic properties, but before establishing a strategy using this bee product, it is necessary to study: (a) the chemical nature of the propolis sample. (b) Propolis efficacy should be compared to well-established parameters, e.g. positive or negative controls in the experiments. Moreover, possible interactions between propolis and other medicines should be investigated in humans as well. (c) Clinical investigation is needed to evaluate propolis potential in patients or healthy individuals, to understand under which conditions propolis may promote health. Data point out the importance of this research field not only for the readers and researchers in the scientific community waiting for further clarification on the potential of propolis but also for the pharmaceutical industry that looks for new drugs. (C) 2010 Elsevier B.V. All rights reserved.

In vitro effects of Crotalus durissus terrificus and Bothrops jararaca venoms on Giardia duodenalis trophozoites

Considering the snake venoms' pharmacological properties and chemotherapeutic potential as well as the need for new alternatives for Giardia infection treatment, the present study was carried out aiming to evaluate the in vitro effects of crude Crotalus durissus terrificus and Bothrops jararaca venoms on the growth and adherence of Giardia duodenalis trophozoites. Trophozoites (10(6)) were exposed to serial twofold dilutions of C. durissus terrificus and B. jararaca venoms that ranged from 3.125 to 200 mu g/ml and from 5 to 320 mu g/ml, respectively. The two venoms inhibited the growth of trophozoites, and the level of inhibition varied according to the assayed concentrations and incubation times. The highest reduction of parasite growth was observed with increasing concentrations of the venoms. No effect on parasite adherence was observed. Light microscope observations revealed changes of the pear-shape aspect of the cell and reduction of flagellar beating frequency in the great part of the trophozoites. This is the first attempt to evaluate the in vitro effects of snake venoms on Giardia trophozoites. The findings stress the need for more investigations and prompt us to perform further studies to identify active principles with antigiardial effect.

Structure determination of a tetrahydro-beta-carboline of arthropod origin: A novel alkaloid-toxin subclass from the web of spider Nephila clavipes

The orb-web spiders are polyphagous animals in which the web plays a very important role in the capture of preys; oily droplets usually cover the capture-web of the spider Nephila clavipes and seem to be of great importance for prey capture. The knowledge of the chemical composition of these droplets is necessary to understand the function of this adhesive material in web mechanics and prey capture. A novel subclass of spider toxins, tetrahydro-beta-carboline, was identified among the weaponry of compounds present inside of oily droplets. This type of alkaloid is not common among the natural compounds of spider toxins. Apparently, when the prey arthropods get caught by the spider web, their bodies are covered with many adhesive oily droplets, which disrupt delivering the tetrahydro-beta-carboline to the direct contact with the prey integument. Toxicity assays demonstrated a potent lethal effect of the alkaloid toxin to the spider preys; topical applications of the teirahydro-beta-carboline at first caused clear signs of neurotoxicity, followed by the death of preys. The structure of the major component, a tetrahydro-beta-carboline, among the alkaloid toxins was elucidated by means of UV spectrophotometry, ESI mass spectrometry, H-1-NMR spectroscopy, and high-resolution mass spectrometry. The structure of the natural toxin was determined as 1-(2-guanidinoethyl)-1,2,3,4-tetrahydro-6-hydroxymethyl)-beta-carboline; the investigation of the pharmacological properties and neurotoxic actions of this compound may be used in the future as reference for the development of new drugs to be applied at level of pest control in agriculture.

Structure determination of hydroxytrypargine: A new tetrahydro-beta-carboline toxin from the venom of the spider Parawixia bistriata

A new, highly active tetrahydro-p-carboline toxin from the spider Parawixia bistriata, the most-common species of social spider occurring in Brazil, was isolated. The new toxin was identified as 1,2,3,4-tetrahydro-6-hydroxy-beta-carboline (= N-[3-(2,3,4,9-tetrahydro-6-hydroxy-1H-pyrido[3,4-b]indol-1-yl)propyl]guanidine; 3). This type of alkaloid, not common among spider toxins, was found to be the most-potent constituent of the spider's chemical weaponry to kill prey. When P bistriata catch arthropods in their web, they apparently attack their prey in groups of many individuals injecting their venoms. In vivo toxicity assays with 3 demonstrated a potent lethal effect to honeybees, giving rise to clear neurotoxic effects (paralysis) before death. The compound's toxicity (LD50 value) was determined to be ca. 8 ng/g of honeybee. The investigation of the pharmacological properties and neurotoxic actions of 3 may be used in the future for the development of new drugs to be applied for pest control in agriculture.

Immunomodulatory effects of tick saliva

Ticks are bloodsucking ectoparasites that cause great damage to host organisms, so these ectoparasites are of great importance in medicine and veterinary medicine. All the biological success achieved by ticks is due to the action of bioactive components present in their saliva, which are synthesized by the salivary glands. These components have great diversity of functions such as enabling feeding and the permanence of ectoparasites on hosts, since they modulate immune system acting as complement inhibitors, immunosuppressors, cytokine expression modulator and chemokine binders of hosts. In addition, these components are an important source of protective antigens. In this sense, salivary glands/saliva are considered a potential source of multifunctional molecules. In this context, many studies have been conducted aiming at searching to establish a better understanding on the biology and morphophysiology of some organs such as salivary glands, as well as elucidate the complex relationship of these ectoparasites with their hosts. Such studies are conducted with the main objective of developing new immunobiological products aimed at the alternative control of ticks, as well as for the identification and isolation of bioactive molecules with pharmacological properties and with great therapeutic potential in the search for treatments for some diseases.

Aspectos químicos, biológicos e etnofarmacológicos do gênero Cassia

Species of Cassia are widely distributed in tropical and subtropical regions throughout the world, and have been extensively investigated chemically and pharmacologically.They are known to be a rich source of phenolic derivatives, most of them with important biological and pharmacological properties. Some Asian, African and Indian tribes use these species as a laxative, purgative, antimicrobial, antipyretic, antiviral and anti-inflammatory agent. Among a number of other classes of secondary metabolites, such as anthracene derivatives, antraquinones, steroids and stilbenoids, biologically active piperidine alkaloids are an especially important bioactive class of compounds that showed to be restricted to a small group of Cassia species. In this paper we present an overview of the chemical, biological and ethnopharmacological data on Cassia piblished in the literature.

Flavonoids with gastroprotective activity

Peptic ulcers are a common disorder of the entire gastrointestinal tract that occurs mainly in the stomach and the proximal duodenum. This disease is multifactorial and its treatment faces great difficulties due to the limited effectiveness and severe side effects of the currently available drugs. The use of natural products for the prevention and treatment of different pathologies is continuously expanding throughout the world. This is particularly true with regards to flavonoids, which represent a highly diverse class of secondary metabolites with potentially beneficial human health effects that is widely distributed in the plant kingdom and currently consumed in large amounts in the diet. They display several pharmacological properties in the gastroprotective area, acting as anti-secretory, cytoprotective and antioxidant agents. Besides their action as gastroprotectives, flavonoids also act in healing of gastric ulcers and additionally these polyphenolic compounds can be new alternatives for suppression or modulation of peptic ulcers associated with H. pylori. In this review, we have summarized the literature on ninety-five flavonoids with varying degrees of antiulcerogenic activity, confirming that flavonoids have a therapeutic potential for the more effective treatment of peptic ulcers.

Preparation and characterization of poly(ε-caprolactone) nanospheres containing the local anesthetic lidocaine

The objective of this work was to develop a modified release system for the local anesthetic lidocaine (LDC), using poly(ε-caprolactone) (PCL) nanospheres (NSs), to improve the pharmacological properties of the drug when administered by the infiltration route. In vitro experiments were used to characterize the system and investigate the release mechanism. The NSs presented a polydispersion index of 0.072, an average diameter of 449.6nm, a zeta potential of -20.1mV, and an association efficiency of 93.3%. The release profiles showed that the release of associated LDC was slower than that of the free drug. Atomic force microscopy analyses showed that the spherical structure of the particles was preserved as a function of time, as well as after the release experiments. Cytotoxicity and pharmacological tests confirmed that association with the NSs reduced the toxicity of LDC, and prolonged its anesthetic action. This new formulation could potentially be used in applications requiring gradual anesthetic release, especially dental procedures. © 2012 Wiley Periodicals, Inc.

Propolis and its constituent caffeic acid suppress LPS-stimulated pro-inflammatory response by blocking NF-κB and MAPK activation in macrophages

Ethnopharmacological relevance Propolis is a bee product with numerous biological and pharmacological properties, such as immunomodulatory and anti-inflammatory activities. It has been used in folk medicine as a healthy drink and in food to improve health and prevent inflammatory diseases. However, little is known about its mechanism of action. Thus, the goal of this study was to verify the antioxidant activity and to explore the anti-inflammatory properties of propolis by addressing its intracellular mechanism of action. Caffeic acid was investigated as a possible compound responsible for propolis action. Materials and methods The antioxidant properties of propolis and caffeic acid were evaluated by using the 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPH) scavenging method. To analyze the anti-inflammatory activity, Raw 264.7 macrophages were treated with different concentrations of propolis or caffeic acid, and nitric oxide (NO) production, a strong pro-inflammatory mediator, was evaluated by the Griess reaction. The concentrations of propolis and caffeic acid that inhibited NO production were evaluated on intracellular signaling pathways triggered during inflammation, namely p38 mitogen-activated protein kinase (MAPK), c-jun NH2-terminal kinase (JNK1/2), the transcription nuclear factor (NF)-κB and extracellular signal-regulated kinase (ERK1/2), through Western blot using specific antibodies. A possible effect of propolis on the cytotoxicity of hepatocytes was also evaluated, since this product can be used in human diets. Results Caffeic acid showed a higher antioxidant activity than propolis extract. Propolis and caffeic acid inhibited NO production in macrophages, at concentrations without cytotoxicity. Furthermore, both propolis and caffeic acid suppressed LPS-induced signaling pathways, namely p38 MAPK, JNK1/2 and NF-κB. ERK1/2 was not affected by propolis extract and caffeic acid. In addition, propolis and caffeic acid did not induce hepatotoxicity at concentrations with strong anti-inflammatory potential. Conclusions Propolis exerted an antioxidant and anti-inflammatory action and caffeic acid may be involved in its inhibitory effects on NO production and intracellular signaling cascades, suggesting its use as a natural source of safe anti-inflammatory drugs. © 2013 Elsevier B.V.

Efeitos do DMSO (dimetilsulfóxido), administrado por via intravenosa, sobre as funções renal e hepática, perfil hidrossalino e hemograma de cães sadios

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)