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.

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.

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.