RESUMO

In Mexico one in 14 deaths are caused by diabetes mellitus (DM) or by the macro and microvascular disorders derived from it. A continuous hyperglycemic state is characteristic of DM, resulting from a sustained state of insulin resistance and/or a dysfunction of ß-pancreatic cells. Acaciella angustissima is a little studied species showing a significant antioxidant activity that can be used as treatment of this disease or preventive against the complications. The objective of this study was to explore the effect of oral administration of A. angustissima methanol extract on physiological parameters of streptozotocin-induced diabetic rats. The results indicated a significant reduction in blood glucose levels, an increase in serum insulin concentration, a decrease in lipid levels and an improvement in the parameters of kidney damage by applying a concentration of 100 mg/Kg B.W. However, glucose uptake activity was not observed in the adipocyte assay. Moreover, the extract of A. angustissima displayed potential for the complementary treatment of diabetes and its complications likely due to the presence of bioactive compounds such as protocatechuic acid. This study demonstrated that methanol extract of Acacciella angustissima has an antidiabetic effect by reducing the levels of glucose, insulin and improved physiological parameters, hypolipidemic effect, oxidative stress and renal damage in diabetic rats.

Assuntos

Diabetes Mellitus Experimental/tratamento farmacológico , Fabaceae/química , Hipolipemiantes/administração & dosagem , Extratos Vegetais/administração & dosagem , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Frutas/química , Humanos , Hipolipemiantes/química , Insulina/sangue , Antagonistas da Insulina/administração & dosagem , Antagonistas da Insulina/química , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/química , Ratos

RESUMO

Advances in the knowledge of the mechanisms controlling protein breakdown in skeletal muscles have allowed the exploration of new options for treating muscle-wasting conditions. Pentoxifylline (PTX), a nonselective phosphodiesterase (PDE) inhibitor, attenuates the loss of muscle mass during catabolic conditions, mainly via inhibiting protein breakdown. The aim of this study was to explore the mechanisms by which PTX inhibits proteolysis in the soleus and extensor digitorum longus (EDL) muscles of streptozotocin-induced diabetic rats. The levels of atrogin-1 and muscle RING finger-1 were decreased, as were the activities of caspase-3 (EDL) and calpains (soleus and EDL), in diabetic rats treated with PTX, which at least partly explains the drop in the ubiquitin conjugate (EDL) levels and in proteasome activity (soleus and EDL). Treatment with PTX decreased PDE activity and increased cAMP content in muscles of diabetic rats; moreover, it also increased both the protein levels of exchange protein directly activated by cAMP (EPAC, a cAMP effector) and the phosphorylation of Akt. The loss of muscle mass was practically prevented in diabetic rats treated with PTX. These findings advance our understanding of the mechanisms underlying the antiproteolytic effects of PTX and suggest the use of PDE inhibitors as a strategy to activate cAMP signaling, which is emerging as a promising target for treating muscle mass loss during atrophic conditions. NEW & NOTEWORTHY cAMP signaling has been explored as a strategy to attenuate skeletal muscle atrophies. Therefore, in addition to ß2AR agonists, phosphodiesterase inhibitors such as pentoxifylline (PTX) can be an interesting option. This study advances the understanding of the mechanisms related to the antiproteolytic effects of PTX on skeletal muscles of diabetic rats, which involve the activation of both exchange protein directly activated by cAMP and Akt effectors, inhibiting the expression of atrogenes and calpain/caspase-3-proteolytic machinery.

Assuntos

Diabetes Mellitus Experimental/complicações , Músculo Esquelético/efeitos dos fármacos , Atrofia Muscular/prevenção & controle , Pentoxifilina/uso terapêutico , Inibidores de Fosfodiesterase/uso terapêutico , Proteólise/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , AMP Cíclico/metabolismo , Avaliação Pré-Clínica de Medicamentos , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Masculino , Músculo Esquelético/metabolismo , Atrofia Muscular/etiologia , Atrofia Muscular/metabolismo , Pentoxifilina/farmacologia , Inibidores de Fosfodiesterase/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/sangue

RESUMO

The present study evaluated the antidiabetic activity of the Combretum lanceolatum Pohl ex Eichler, Combretaceae, flowers extract (ClEtOH) in diabetic rats. Streptozotocin-diabetic rats were divided into four groups: diabetic control, diabetic treated with 500 mg/kg of metformin and diabetic treated with 250 or 500 mg/kg of ClEtOH for 21 days. The treatment of diabetic rats with 500 mg/kg of ClEtOH promoted an increase in the weight of liver, white adipose tissues and skeletal muscles, improving body weight gain. Diabetic rats treated with 500 mg/kg of ClEtOH also presented reduction in glycemia, glycosuria and urinary urea levels, and increase in liver glycogen content. HPLC chromatogram showed that quercetin is the major compound in the extract. The phosphorylation levels of adenosine monophosphate-activated protein kinase were increased in liver slices incubated in vitro with 50 µg/mL of ClEtOH, similarly to the incubation with metformin (50 µg/mL) or quercetin (10 µg/mL). The antihyperglycemic effect of ClEtOH was similar to that of metformin and appears to be through inhibition of gluconeogenesis, since urinary urea was reduced and skeletal muscle mass was increased. These data indicate that the antidiabetic activity of the Combretum lanceolatum extract could be mediated, at least in part, through activation of adenosine monophosphateactivated protein kinase by quercetin.