Abstract Although there are reports that polyphenol resveratrol (Rsv) may cause muscle hypertrophy in basal conditions and attenuate muscle wasting in catabolic situations, its mechanism of action is still unclear. Our study evaluated the ex vivo effects of Rsv on protein metabolism and intracellular signaling in innervated (sham-operated; Sham) and 3-day sciatic denervated (Den) rat skeletal muscles. Rsv (10-4 M) reduced total proteolysis (40%) in sham muscles. Den increased total proteolysis (~40%) in muscle, which was accompanied by an increase in the activities of ubiquitin-proteasome (~3-fold) and lysosomal (100%) proteolytic systems. Rsv reduced total proteolysis (59%) in Den muscles by inhibiting the hyperactivation of ubiquitin-proteasome (50%) and lysosomal (~70%) systems. Neither Rsv nor Den altered calcium-dependent proteolysis in muscles. Mechanistically, Rsv stimulated PKA/CREB signaling in Den muscles, and PKA blockage by H89 (50μM) abolished the antiproteolytic action of the polyphenol. Rsv reduced FoxO4 phosphorylation (~60%) in both Sham and Den muscles and Akt phosphorylation (36%) in Den muscles. Rsv also caused a homeostatic effect in Den muscles by returning their protein synthesis rates to levels similar to Sham muscles. These data indicate that Rsv directly inhibits the proteolytic activity of lysosomal and ubiquitin-proteasome systems, mainly in Den muscles through, at least in part, the activation of PKA/CREB signaling. (Rsv situations unclear shamoperated operated (sham-operated 3day day 3 (Den 104 10 4 (10- M 40% 40 (40% ~40% (~40% ubiquitinproteasome ubiquitin proteasome ~3fold 3fold fold ~3 (~3-fold 100% 100 (100% systems 59% 59 (59% 50% 50 (50% ~70% 70 (~70% calciumdependent calcium dependent Mechanistically PKACREB CREB H H8 50μM μM (50μM FoxO ~60% 60 (~60% 36% 36 (36% through part 1 (10 (40 ~40 (~40 ~ (100 5 (59 (50 ~70 7 (~70 ~60 6 (~60 (36 (1 (4 ~4 (~4 (5 ~7 (~7 ~6 (~6 (3 ( (~

Abstract Morus nigra L. has been widely used in Brazilian folk medicine for the treatment of diabetes. We evaluate the chemical composition and antidiabetic properties of the hexane (Hex-Mn) and chloroform (Chlo-Mn) fractions obtained by partition of the crude ethanolic extract from the leaves in rats. Chemical composition analysis of Hex-Mn and Chlor-Mn was performed by gas chromatography-mass spectrometry (CG-MS). In vivo and in vitro studies were carried out to compare the antidiabetic activities of the Hex-Mn and Chlor-Mn fractions. Most of the compounds identified in Hex-Mn were α-linolenic acid, stigmast-5-en-3-ol and linolenic acid ethyl ester, while in Chlor-Mn, stigmast-5-en-3-ol, palmitic acid and α-linolenic acid were mainly identified. Only Hex-Mn treatment reduced both fasting and postprandial hyperglycemia. Additionally, Hex-Mn preserved body weight gain, preserved the hepatic glycogen content, and also reduced the thiobarbituric acid reactive substances and nitrite levels, as well as restored the superoxide dismutase. Furthermore, digestion of complex carbohydrates and intestinal glucose absorption was prevented by Hex-Mn treatment. Our results suggest that the antidiabetic activity of Hex-Mn may be explained, at least in part, by the insulin sensitivity increase, antioxidant properties and reduction in carbohydrate absorption in the small intestine.

ABSTRACT Rhizophora mangle is an abundant plant in mangroves and tannic acid is a polyphenol produced by the secondary metabolism of plants. The aim of the study was to evaluate the embryotoxic and embriostatic effects of the aqueous extract of R. mangle and synthetic tannic acid on eggs and larvae of Aedes aegypti. A. aegypti eggs were exposed in duplicate at concentrations of 250, 500, 750 and 1000 µg/mL of extract and tannic acid for a period of 14 days. Mineral water was used as a negative control. The eggs were observed and counted in a stereomicroscope (1.2x). In all extract concentrations there was stimulation in hatching in relation to the control, but only in concentration of 750 mg/mL it was statistically significant. In tannic acid (250µg/ml) there was significant stimulus in hatching, but in 500, 750 and 1000 µg/mL there was significant inhibition. All concentrations of aqueous extract and tannic acid on larvae showed embryotoxic and embryostatic effects when compared to the control. The aqueous extract of R. mangle showed effect on hatching of A. aegypti eggs and synthetic tannic acid showed embryotoxic and embryostatic effects. On larvae, both the aqueous extract as tannic acid showed embryotoxic and embryostatic effects.

RESUMO: Este estudo avaliou a toxicidade aguda e crônica de um inseticida a base de tiametoxam para peixes da espécie Pacamã (Lophisiolurus alexandri), avaliando a CL50%, além de alterações histopatológicas hepáticas em animais expostos por 96 horas e 15 dias ao inseticida. Para tanto foram utilizados 120 alevinos submetidos a cinco diferentes concentrações do inseticida (30, 60, 120, 240 e 480mg/L) por 15 dias, com dois tempos amostrais, 96 horas e 15 dias. Não houve mortalidade significativa durante todo o período experimental, no entanto os animais apresentaram alterações como vacuolização citoplasmática, congestão e necrose. A CL50% foi determinada como superior a 100mg/L, considerada praticamente não tóxico. A necrose foi a alteração melhor evidenciada nos animais expostos, com o aumento da ocorrência nos animais do teste de toxicidade crônica.

ABSTRACT: This research evaluated acute and chronic toxicity of a thiamethoxam insecticide for Pacamã (Lophisiolurus alexandri), assessing the LC50 and liver histopathological changes in animals exposed for 96 hours and 15 days. Therefore, were used 120 fingerlings subjected to five different concentrations (30, 60, 120, 240 and 480mg/L) for 15 days with two sampling times, 96 hours and 15 days. There was no significant mortality during the experimental period, however the animals showed changes as vacuolation, congestion and necrosis. The LC50 was determined as greater than 100mg/L, considered practically non-toxic. Necrosis was the more significant change in exposed animals, with increasing occurrence in chronic toxicity test.

RESUMO Os manguezais representam zonas de elevada produtividade biológica sendo uma das regiões mais ricas em substâncias bioativas utilizadas na produção de medicamentos. Conocarpus erectus (Combretaceae) conhecida como mangue botão é uma das espécies encontrada nos manguezais e é utilizada na medicina popular no tratamento de anemia, catarro, conjuntivite, diabetes, diarréia, febre, gonorréia, dor de cabeça, hemorragia, orquite, brotoeja, inchaços e sífilis. O presente estudo objetivou investigar a toxicidade aguda de extrato aquoso de folhas de C. erectus em camundongos albinos suíços. O material vegetal foi coletado no manguezal de Vila Velha, localizado em Itamaracá (PE). O material foi submetido a um screening fitoquímico onde foram usados protocolos extrativos de identificação de moléculas majoritárias presentes nas folhas. A avaliação da toxicidade aguda do extrato aquoso de C. erectus seguiu o modelo da Toxicidade Aguda de Classe baseado no Guia da OECD 423, 2001. As moléculas majoritárias identificadas foram: flavonóides, taninos e saponinas. A DL50 foi estimada em 2.000 mg/Kg p.c. Portanto, o extrato apresentou baixa toxicidade aguda classificada na categoria 5.

ABSTRACT Mangroves represent areas of high biological productivity and it is a region rich in bioactive substances used in medicine production. Conocarpus erectus (Combretaceae) known as button mangrove is one of the species found in mangroves and it is used in folk medicine in the treatment of anemia, catarrh, conjunctivitis, diabetes, diarrhea, fever, gonorrhea, headache, hemorrhage, orchitis, rash, bumps and syphilis. The present study aimed to investigate the acute toxicity of aqueous extract of leaves of C. erectus in Swiss albino mice. The plant material was collected in Vila Velha mangroves, located in Itamaracá (PE). The material was subjected to a phytochemical screening where extractive protocols to identify majority molecules present in leaves were used. The evaluation of acute toxicity of aqueous extract of C. erectus followed the model of Acute Toxicity Class based on OECD 423 Guideline, 2001. The majority molecules were identified: flavonoids, tannins and saponins. The LD50 was estimated at 2,000 mg/kg bw. Therefore, the aqueous extract showed low acute toxicity classified in category 5.

RESUMO Spondias tuberosa Arruda, popularmente conhecida como umbu, é uma espécie nativa da Caatinga amplamente utilizada na medicina popular, cujo perfil toxicológico ainda não é conhecido. Deste modo, este estudo avaliou o perfil fitoquímico, a toxicidade aguda e a citotoxicidade do extrato etanólico da casca da Spondias tuberosa Arruda (EEStb) nos parâmetros hematológicos, bioquímicos e histopatológicos. Foram utilizados ratos fêmeas Wistar (±210g) e divididos em: grupo controle (C) e tratados com uma dose única de 300mg/Kg (EEStb300) ou 2.000mg/kg do peso corporal (ESStb2.000) do EEStb. Após 24 horas e 14 dias da gavagem, os parâmetros comportamentais, hematológicos, bioquímicos e histopatológicos foram determinados. O efeito citotóxico foi avaliado em células HEp-2. Não foi observada mortalidade ou alterações de massa corporal durante os 14 dias de experimento nos grupos EEStb300 e EEStb2.000, mas EEStb2.000 provocou uma redução discreta no consumo hídrico e alimentar, assim como na atividade locomotora no 1º dia de tratamento. Não houve alterações nos parâmetros histopatológicos, macroscópicos, bioquímicos e hematológicos. EEStb2000 nas concentrações de 6.25-50μg.ml-1) não produziu efeito citotóxico. na célula HEp-2. Estes resultados sugerem que EEStb não promoveu toxicidade aguda ou citotóxica, sugerindo boa margem de segurança para uso da Spondias tuberosa Arruda.

ABSTRACT Spondias tuberosa Arruda, popularly named as umbu, is native from savanna-like vegetation and widely used for medicinal purposes, however, the toxicological profile is not available yet. This study evaluated the phytochemical profile and acute toxicity and citoxicity of Ethanolic Extract of Spondias tuberosa Arruda Bark (EEStb) in hematological, biochemical and histopathological parameters. Female Wistar rats were divided into: control (C) and animal treated single doses of 300mg/Kg (EEStb300) or 2.000mg/kg body weight (ESStb2.000) of the EEStb. After 24 hours and 14 days from gavage, the behavior, hematological, biochemical and histopathological parameters were assayed. Cytotoxicity effect was evaluated on HEp-2 cell lines. Neither EEStb300 nor EEStb2.000 produced mortality nor changes in body weight during the 14-days of observation, but EEStb2.000 reduced quietly the food and water intake as well as locomotor activity at first day. There were no changes in macroscopic, histopathological, biochemical and hematological parameters. EEStb in concentrations of 6.25- 50μg ml−1 on HEp-2 cell did not produce cytotoxic effect. These results suggest that EEStb did not cause acute toxicity and cytotoxic, suggesting a good safety rate for Spondias tuberosa Arruda.

O presente trabalho objetivou comparar o fluxo de calor sensível obtido pelo método do balanço de energia-razão de Bowen (H_B) e pelo método aerodinâmico (H_A), em uma área de 4 ha cultivada com feijão-caupi em Areia-PB (6º 58' 12" S e 35º 42' 15" O, 620 m). Foram coletados dados de saldo de radiação, fluxo de calor no solo, temperatura e umidade do solo, temperatura e umidade relativa do ar, velocidade do vento e precipitação pluvial, os quais eram lidos a cada minuto, e armazenados, em uma central de aquisição de dados, como médias a cada 30 min, com exceção da pluviometria, cujo valor foi totalizado no período. Obteve-se excelente concordância entre H_A e H_B, com um índice "d " de 0,980, um erro padrão (EP) de 14,88 W m-2, e sem diferença significativa entre H_A e H_B, pelo teste t-Student. Deste modo, o método aerodinâmico pode ser usado em conjunto com medidas de saldo de radiação e de fluxo de calor no solo, para se estimar o fluxo de calor latente e, consequentemente, a evapotranspiração da cultura do feijão-caupi, para as condições edafoclimáticas do Brejo Paraibano.

A study was performed to compare the bulk aerodynamic (H_A) and Bowen ratio energy balance (H_B) methods in the estimation of the sensible heat flux in a cowpea crop. Data of net radiation, soil heat flux, soil water content, soil temperature, air temperature, relative humidity, wind speed and rainfall were collected on 30-min time intervals in an area of 4 ha belonging to the municipality of Areia, PB (6º 58' 12" S e 35º 42' 15" W, 620 m). Results showed that there was a good agreement between H_A and H_B with an index "d" of 0.98 and standard error of estimate (SEE) of 14.88 W m-2, no significant difference between H_A H_B, by the t-Student test. Thus, the bulk aerodynamic method can be used in conjunction with measurements of net radiation and soil heat flux to estimate the evapotranspiration of the cowpea under soil and climatic condition of the "Brejo Paraibano".

The present investigation reports the isolation of aeroplysinin-2, 2-(3,5-dibromo-4-methoxyphenyl)-N,N,N-trimethyletanamonium, 7,9-dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,6,8-trien-3-carboxylic acid and its methyl ester, 11-oxoaerothionin, aerothionin, 11-keto-12-hydroxyaerothionin, 11-ketofistularin-3 and fistularin-3 from Aplysina fistularis, as well as of furodysinin lactone and 9α,11α-epoxicholest-7-en-3β,5α,6α,10-tetrol-6-acetate from Dysidea sp. Although the extracts of both sponges displayed antituberculosis activity, only 11-ketofistularin-3 isolated from A. fistularis displayed antimycobacterial activity against Mycobacterium tuberculosis H34Rv, with MIC at 16 μg/mL and SI of 40, a result that reinforce that fistularin-3 derivatives are interesting leads for the development of antituberculosis drugs.

The investigation of extracts from six species of marine invertebrates yielded one new and several known natural products. Isoptilocaulin from the sponge Monanchora aff. arbuscula displayed antimicrobial activity at 1.3 mg/mL against an oxacillin-resistant strain of Staphylococcus aureus. Five inactive known dibromotyrosine derivatives, 2 6, were isolated from a new species of marine sponge, Aplysina sp. The sponges Petromica ciocalyptoides and Topsentia ophiraphidites yielded the known halistanol sulfate A (7) as an inhibitor of the antileishmanial target adenosine phosphoribosyl transferase. The ascidian Didemnum ligulum yielded asterubin (10) and the new N,N-dimethyl-O-methylethanolamine (11). The octocoral Carijoa riisei yielded the known 18-acetoxypregna-1,4,20-trien-3-one (12), which displayed cytotoxic activity against the cancer cell lines SF295, MDA-MB435, HCT8 and HL60.

No presente estudo apresentamos resultados da triagem biológica realizada com 349 extratos obtidos de esponjas marinhas, ascídias, briozoários e octocorais do Brasil, em testes contra 16 linhagens de bactérias comuns e resistentes à antibióticos, uma levedura (Candida albicans), Mycobacterium tuberculosis H37Rv, três linhagens de células tumorais MCF-7 (mama), B16 (melanoma murínico) e HCT8 (cólon), e de inibição da enzima adenina fosforribosil transferase de Leishmania tarentolae (L-APRT). Menos de 15% dos extratos de esponja marinhas apresentaram atividade antibacteriana, contra linhagens resistentes ou não a antibióticos. Quase 40% dos extratos de esponjas marinhas apresentaram atividade antimicobacteriana contra Mycobacterium tuberculosis H37Rv. Foi observada citotoxicidade para 18% dos extratos de esponjas marinhas. Finalmente, menos de 3% dos extratos de esponjas apresentaram atividade inibitória da enzima L-APRT. Menos de 10% dos extratos de ascídias apresentaram atividade antibacteriana. Mais de 25% dos extratos de ascídias apresentaram atividade contra M. tuberculosis e as três linhagens de células tumorais. Somente dois extratos obtidos da ascídia Polysyncraton sp. coletada em duas diferentes épocas (1995 e 1997) apresentaram atividade contra L-APRT. Menos de 2% dos extratos de briozoários e octocorais apresentaram atividade antibacteriana, mas uma alta percentagem de extratos destes animais apresentaram atividades citotóxica (11% e 30%, respectivamente) e antimicobacteriana (60%). O extrato de somente uma espécie de briozoário, Bugula sp., apresentou atividade inibitória da enzima L-APRT. A análise taxonômica de algumas espécies de invertebrados que forneceram alguns dos extratos mais ativos, indicou a ocorrência de atividade biológica em espécies pertencentes a grupos taxonômicos que já foram anteriormente investigados do ponto de vista químico. Estes incluem esponjas marinhas pertencentes aos gêneros Aaptos, Aplysina, Callyspongia, Haliclona, Niphates, Cliona, Darwinella, Dysidea, Ircinia, Monanchora e Mycale, ascídias dos gêneros Didemnum, Aplidium, Botrylloides, Clavelina, Polysyncraton e Symplegma, o briozoário Bugula sp. e octocorais dos gêneros Carijoa e Lophogorgia. A subseqüente investigação química de alguns dos extratos ativos levou ao isolamento de vários metabólitos secundários biologicamente ativos. Os resultados obtidos estão de acordo com resultados obtidos em programas de triagem de atividade biológica de extratos brutos de invertebrados marinhos anteriormente reportados, que apresentaram altas percentagens de extratos bioativos oriundos de Porifera, Ascidiacea, Cnidária e Bryozoa.

Herein we present the results of a screening with 349 crude extracts of Brazilian marine sponges, ascidians, bryozoans and octocorals, against 16 strains of susceptible and antibiotic-resistant bacteria, one yeast (Candida albicans), Mycobacterium tuberculosis H37Rv, three cancer cell lines MCF-7 (breast), B16 (murine melanoma ) and HCT8 (colon), and Leishmania tarentolae adenine phosphoribosyl transferase (L-APRT) enzyme. Less than 15% of marine sponge crude extracts displayed antibacterial activity, both against susceptible and antibiotic-resistant bacteria. Up to 40% of marine sponge crude extracts displayed antimycobacterial activity against M. tuberculosis H37Rv. Cytotoxicity was observed for 18% of marine sponge crude extracts. Finally, less than 3% of sponge extracts inhibited L-APRT. Less than 10% of ascidian crude extracts displayed antibacterial activity. More than 25% of ascidian crude extracts were active against M. tuberculosis and the three cancer cell lines. Only two crude extracts from the ascidian Polysyncraton sp. collected in different seasons (1995 and 1997) displayed activity against L-APRT. Less than 2% of bryozoan and octocoral crude extracts presented antibacterial activity, but a high percentage of crude extracts from bryozoan and octororal displayed cytotoxic (11% and 30%, respectively) and antimycobacterial (60%) activities. The extract of only one species of bryozoan, Bugula sp., presented inhibitory activity against L-APRT. Overall, the crude extracts of marine invertebrates herein investigated presented a high level of cytotoxic and antimycobacterial activities, a lower level of antibacterial activity and only a small number of crude extracts inhibited L-APRT. Taxonomic analysis of some of the more potently active crude extracts showed the occurrence of biological activity in taxa that have been previously chemically investigated. These include marine sponges belonging to genera Aaptos, Aplysina, Callyspongia, Haliclona, Niphates, Cliona, Darwinella, Dysidea, Ircinia, Monanchora and Mycale, ascidians of the genera Didemnum, Aplidium, Botrylloides, Clavelina, Polysyncraton and Symplegma, the bryozoan Bugula sp. and octocorals of the genera Carijoa and Lophogorgia. The subsequent chemical investigation of some of the active extracts led to the isolation of several new biologically active secondary metabolites. Our results are in agreement with previous screening programs carried out abroad, that showed a high percentage of bioactive extracts from Porifera, Ascidiacea, Cnidaria and Bryozoa.