Fruit of the jambolan tree (Eugenia jambolana Lam.) and experimental diabetes

The fruit of Indian Eugenia jambolana have been shown to have therapeutic properties, but because the therapeutic potential of a plant is related to the geographic region in which the plant was grown and to the part of the plant used, we investigated Brazilian Eugenia jambolana fruit using the same preparation and experimental methods as have been used in India. The well-established metabolic cage model was used to evaluate the physiological and metabolic parameters associated with streptozotocin-induced diabetes in rats (n = 10) which had been administered, by gavage, 50 mg per day of lyophilised Eugenia jambolana fruit-pulp extract for 41 days. We found that, compared to untreated controls, rats treated with the lyophilised fruit-pulp showed no observable difference in body weight, food or water intake, urine volume, glycaemia, urinary urea and glucose, hepatic glycogen, or on serum levels of total cholesterol, HDL cholesterol or triglycerides. No change was observed in the masses of epididymal or retroperitoneal adipose tissue or of soleus or extensor digitorum longus muscles. This lack of any apparent effect on the diabetes may be attributable to the regional ecosystem where the fruit was collected and/or to the severity of the induced diabetes. (C) 2004 Elsevier B.V.. All rights reserved

A low-protein, high-carbohydrate diet increases the adipose lipid content without increasing the glycerol-3-phosphate or fatty acid content in growing rats

Le taux de triacylglycerol (TAG) qui s`accumule dans le tissu adipeux depend de 2 mecanismes opposes : la lipogenese et la lipolyse. Nous avons montre anterieurement que le poids des lipides du tissu adipeux de l`epididyme (EPI) de meme que leur taux augmentent chez les rats en croissance soumis a une diete hypoproteique hyperglucidique (HPHG) pendant 15 jours. La presente etude a eu pour but d`examiner les voies impliquees dans la lipogenese et la lipolyse qui regulent l`accumulation des lipides dans le tissu. On a evalue in vivo la synthese de novo des acides gras, qui s`est revelee similaire chez les rats soumis a la diete HPHG ou a une diete temoin; toutefois, chez les rats soumis a la diete HPHG, une diminution de l`activite de la lipoproteine lipase dans le tissus adipeux de l`EPI a ete observee, ce qui laisse croire a une diminution de la capture des acides gras des lipoproteines circulantes. La diete HPHG n`a eu aucun effet sur la synthese du glycerol-3-phosphate (G3P) par la glycolyse ou la glyceroneogenese. L`activite de la glycerokinase, c.-a-d. la phosphorylation du glycerol issu de l`hydrolyse du TAG endogene pour former le GP3, n`a pas ete modifiee non plus par la diete HPHG. A l`oppose, les adipocytes des rats HPHG stimules par la norepinephrine ont eu une plus faible reponse lipolytique, meme si le taux lipolytique basal des adipocytes a ete similaire chez les 2 groupes. Ainsi, les resultats donnent a penser que la diminution de l`activite lipolytique stimulee par la norepinephrine joue un role essentiel dans l`augmentation du TAG observee dans le tissu adipeux de l`EPI des animaux HPHG, probablement en perturbant le processus d`activation de la lipolyse.Fundacao de Amparo a Pesquisa do Estado de Mato Grosso (FAPEMAT)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES

Novel Selective and Low-Toxic Inhibitor of LmCPB2.8ΔCTE (CPB) One Important Cysteine Protease for Leishmania Virulence

Leishmaniasis is a highly prevalent, yet neglected disease caused by protozoan parasites of the genus Leishmania. In the search for newer, safer, and more effective antileishmanial compounds, we herein present a study of the mode of action in addition to a detailed structural and biological characterization of LQOF-G6 [N-benzoyl-N′-benzyl-N″-(4-tertbutylphenyl)guanidine]. X-ray crystallography and extensive NMR experiments revealed that LQOF-G6 nearly exclusively adopts the Z conformation stabilized by an intramolecular hydrogen bond. The investigated guanidine showed selective inhibitory activity on Leishmania major cysteine protease LmCPB2.8ΔCTE (CPB) with ~73% inhibition and an IC50-CPB of 6.0 µM. This compound did not show any activity against the mammalian homologues cathepsin L and B. LQOF-G6 has been found to be nontoxic toward both organs and several cell lines, and no signs of hepatotoxicity or nephrotoxicity were observed from the analysis of biochemical clinical plasma markers in the treated mice. Docking simulations and experimental NMR measurements showed a clear contribution of the conformational parameters to the strength of the binding in the active site of the enzyme, and thus fit the differences in the inhibition values of LQOF-G6 compared to the other guanidines. Furthermore, the resulting data render LQOF-G6 suitable for further development as an antileishmanial drug