Evaluation of gastroprotective activity of Plinia edulis (Vell.) Sobral (Myrtaceae) leaves in rats

Plinia edulis, an arboreous species popularly known as ""cambuca"", is native to the Brazilian Atlantic Rain Forest. Despite its traditional uses, no reports are available on the safety of this utilization or on the relationship between the antiulcer activity of its extract and its phytochemical compounds. This paper reports on the investigation of the acute toxicity and gastroprotective effect of the aqueous ethanol extract of leaves of Plinia edulis on HCl/ethanol-induced ulcers. In order to correlate the secondary metabolites and the efficacy of the crude drug in traditional medicine, the extract was submitted to chromatographic fractionation after solvent partition. The extract did not show acute toxicity in mice treated with 5 g/kg p.o.. but exhibited significant antiulcer activity in rats at doses of 100, 200, and 400 mg/kg p.o., more active than the reference drug lansoprazole. The ethyl acetate fraction yielded P-amyrin, oleanolic acid, ursolic acid, and maslinic acid, which were identified based on spectrometric analyses. Since antiulcerogenic activity is not restricted to one class of compounds in plants, the triterpenoids isolated in the extract can be associated with the observed effect. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Antileishmanial activity screening of 5-nitro-2-heterocyclic benzylidene hydrazides

A series of 53 nitro derivatives rationally designed were obtained by parallel synthesis and screened against Leishmania donovani. Six compounds exhibited IC(50) values lower than standard drugs. Brief SAR analysis revealed that substitution is important to the activity. Nitrothiophene analogues were more potent than the nitrofuran ones. This was attributed to the ability of sulfur atoms in accommodating electrons from nitro group, which facilitate its reduction and therefore the formation of free radicals lethal to parasites. (c) 2008 Elsevier Ltd. All rights reserved.

Influence of Pluronic (R) F68 on Ceftazidime Biological Activity in Parenteral Solutions

beta-Lactam antimicrobials are known to have a low concentration/therapeutic response. However, extending the period in which beta-lactam are free in the plasma does directly influence therapeutic outcomes. The objective of this study was to evaluate the influence of Pluronic (R) F68 on the antimicrobial activity of ceftazidime when admixed with aminophylline in parenteral solutions by the evaluation of its minimal inhibitory concentration (MIC) within 24 h. Ceftazidime, aminophylline, and Pluronics (R) F68 were evaluated using the MIC method against Escherichia coli and Pseudomonas aeruginosa, with these compounds individually and associated in the same parenteral solutions. When Pluronics (R) F68 was admixtured with ceftazidime alone or with ceftazidime and aminophylline, it was possible to observe lower MIC values not only at 24 h but also at 0 h for both microorganisms. This indicates that Pluronics (R) F68 may be able to enhance ceftazidime antimicrobial activity in the presence or absence of aminophylline. This fact suggests that Pluronics (R) F68 can be applied to allow the administration of ceftazidime under continuous infusion in parenteral solutions, beneficiating hospital pharmacotherapy. It may also be possible to reduce ceftazidime doses in formulations achieving the same therapeutic results. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:715-720, 2011

The behavior of key enzymes of xylose metabolism on the xylitol production by Candida guilliermondii grown in hemicellulosic hydrolysate

A variety of raw materials have been used in fermentation process. This study shows the use of rice straw hemicellulosic hydrolysate, as the only source of nutrient, to produce high added-value products. In the present work, the activity of the enzymes xylose reductase (XR); xylitol dehydrogenase (XD); and glucose-6-phosphate dehydrogenase (G6PD) during cultivation of Candida guilliermondii on rice straw hemicellulosic hydrolysate was measured and correlated with xylitol production under different pH values (around 4.5 and 7.5) and initial xylose concentration (around 30 and 70 g l(-1)). Independent of the pH value and xylose concentration evaluated, the title of XD remained constant. On the other hand, the volumetric activity of G6PD increased whereas the level of XR decreased when the initial xylose concentration was increased from 30 to 70 g l(-1). The highest values of xylitol productivity (Q (P) a parts per thousand 0.40 g l(-1)) and yield factor (Y (P/S) a parts per thousand 0.60 g g(-1)) were reached at highest G6PD/XR ratio and lowest XR/XD ratio. These results suggest that NADPH concentrations influence the formation of xylitol more than the activity ratios of the enzymes XR and XD. Thus, an optimal rate between G6PD and XR must be reached in order to optimize the xylitol production.

Characterization of Brazilian lager and brown ale beers based on color, phenolic compounds, and antioxidant activity using chemometrics

BACKGROUND: Epidemiological studies have shown that beer has positive effects on inhibiting atherosclerosis, decreasing the content of serum low-density lipoprotein cholesterol and triglycerides, by acting as in vivo free radical scavenger. In this research, the antioxidant activity of commercial Brazilian beers (n = 29) was determined by the oxygen radical absorbance capacity (ORAC) and 1,1 -diphenyl-2-picrylhydrazyl (DPPH(center dot)) assays and results were analyzed by chemometrics. RESULTS: The brown ale samples (n = 11) presented higher (P < 0.05) flavonoids (124.01 mg L(-1)), total phenolics (362.22 mg L(-1)), non-flavonoid phenolics (238.21 mg L(-1)), lightness (69.48), redness (35.75), yellowness (55.71), color intensity (66.86), hue angle (59.14), color saturation (0.9620), DPPH(center dot) values (30.96% inhibition), and ORAC values (3,659.36 mu mol Trolox equivalents L(-1)), compared to lager samples (n = 18). Brown ale beers presented higher antioxidant properties (P < 0.05) measured by ORAC (1.93 times higher) and DPPH (1.65 times higher) compared to lager beer. ORAC values correlated well with the content of flavonoids (r = 0.47; P = 0.01), total phenolic compounds (r = 0.44; P < 0.01) and DPPH (r = 0.67; P < 0.01). DPPH values also correlated well to the content of flavonoids (r = 0.69; P < 0.01), total phenolic compounds (r = 0.60; P < 0.01), and non-flavonoid compounds (r = 0.46; P = 0.01). CONCLUSION: The results suggest that brown ale beers, and less significantly lager beers, could be sources of bioactive compounds with suitable free radical scavenging properties. (C) 2010 Society of Chemical Industry

Phenolic compounds content and antioxidant activity in pomace from selected red grapes (Vitis vinifera L. and Vitis labrusca L.) widely produced in Brazil

The phenolic compounds content and antioxidant activity of pomace from the vinification of grape varieties widely produced in Brazil (Cabernet Sauvignon, Merlot, Bordeaux and Isabel) were investigated with a view to their exploitation as a potential source of natural antioxidants. Cabernet Sauvignon grape pomace was found to have the highest content of total phenolic compounds (74.75 mg gallic acid equivalent (GAE)/g), the highest antioxidant activity (determined using the 2,2`-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging methods; 485.42 and 505.52 mu Mol Trolox equivalent antioxidant capacity (TEAC)/g, respectively), and the highest reducing power (determined using the FRAP method; 249.46 mu Mol TEAC/g). The Bordeaux variety showed the highest oxidation inhibition power (41.13%), determined using the beta-carotene/linoleic acid method and the highest content of total anthocyanins (HPLC; 29.17 mg/g). Catechin was the most abundant non-anthocyanic compound identified in the grape pomace (150.16 mg/100 g) for all varieties. In this study, pomaces of the red wine vinification of Cabernet Sauvignon and Bordeaux varieties showed the highest potential as a source of antioxidant compounds and natural colourants, respectively. (C) 2011 Elsevier Ltd. All rights reserved.

Synergism on antioxidant activity between natural compounds optimized by response surface methodology

Despite the increase in the use of natural compounds in place of synthetic derivatives as antioxidants in food products, the extent of this substitution is limited by cost constraints. Thus, the objective of this study was to explore the synergism on the antioxidant activity of natural compounds, for further application in food products. Three hydrosoluble compounds (x(1) = caffeic acid, x(2) = carnosic acid, and x(3) = glutathione) and three liposoluble compounds (x(1) = quercetin, x(2) = rutin, and x(3) = genistein) were mixed according to a ""centroid simplex design"". The antioxidant activity of the mixtures was analyzed by the ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAL) methodologies, and activity was also evaluated in an oxidized mixed micelle prepared with linoleic acid (LAOX). Cubic polynomial models with predictive capacity were obtained when the mixtures were submitted to the LAOX methodology ((y) over cap = 0.56 x(1) + 0.59 x(2) + 0.04 x(3) + 0.41 x(1)x(2) - 0.41 x(1)x(3) - 1.12 x(2)x(3) - 4.01 x(1)x(2)x(3)) for the hydrosoluble compounds, and to FRAP methodology ((y) over cap = 3.26 x(1) + 2.39 x(2) + 0.04 x(3) + 1.51 x(1)x(2) + 1.03 x(1)x(3) + 0.29 x(1)x(3) + 3.20 x(1)x(2)x(3)) for the liposoluble compounds. Optimization of the models suggested that a mixture containing 47% caffeic acid + 53% carnosic acid and a mixture containing 67% quercetin + 33% rutin were potential synergistic combinations for further evaluation using a food matrix.

Design, synthesis, antimicrobial activity and molecular modeling studies of novel benzofuroxan derivatives against Staphylococcus aureus

Molecular modi. cation is a quite promising strategy in the design and development of drug analogs with better bioavailability, higher intrinsic activity and less toxicity. In the search of new leads with potential antimicrobial activity, a new series of 14 4-substituted [N`-(benzofuroxan-5-yl) methylene] benzohydrazides, nifuroxazide derivatives, were synthesized and tested against standard and multidrug-resistant Staphylococcus aureus strains. The selection of the substituent groups was based on physicochemical properties, such as hydrophobicity and electronic effect. These properties were also evaluated through the lipophilic and electrostatic potential maps, respectively, considering the compounds with better biological pro. le. Twelve compounds exhibited similar bacteriostatic activity against standard and multidrug-resistant strains. The most active compound was the 4-CF(3) substituted derivative, which presented a minimum inhibitory concentration (MIC) value of 14.6-13.1 mu g/mL, and a ClogP value of 1.87. The results highlight the benzofuroxan derivatives as potential leads for designing new future antimicrobial drug candidates. (C) 2009 Elsevier Ltd. All rights reserved.

Gastric anti-ulcer activity of leaf fractions obtained of polar extract from Wilbrandia ebracteata in mice

Leaf fractions of Wilbrandia ebracteata were investigated for anti-ulcerogenic effects in ethanol and indomethacin-induced gastric ulcer assays in mice. Protective anti-ulcer effects were detected only in the ethanol-induced ulcer assay effects after pre-treatment with MeOH extract, MeOH chlorophyll-free, chlorophyll residue, HEX, DCM, aqueous MeOH fraction, ethyl acetate (EtOAc) and aqueous fractions. A potent anti-ulcerogenic effect was determined after pre-treatment of animals with EtOAc fraction, which was fractionated for isolation of active constituents. Seven flavonoids, 3`,4`,5,6,7,8-hexahydroxyflavonol, orientin, isoorientin, vitexin, isovitexin, luteolin, 6-methoxi-luteolin were isolated from the leaves of W. ebracteata (Cucurbitaceae) by chromatographic methods and identified by their spectral data. The data suggest that flavonoids are active anti-ulcerogenic compounds from leaves of W. ebracteata. The ability of scavenging free radicals was evaluated by DPPH reduction assay by TLC of flavonoids isolated.

Cytotoxic activity of a dichloromethane extract and fractions obtained from Eudistoma vannamei (Tunicata: Ascidiacea)

This study consists of the bioassay-guided fractionation of the dichloromethane extract from Eudistoma vannamei and the pharmacological characterization of the active fractions. The dried hydromethanolic extract dissolved in aqueous methanol was partitioned with dichloromethane and chromatographed on a silica gel flash column. The anti-proliferative effect was monitored by the MTT assay. Four of the latest fractions, numbered 14 to 17, which held many chemical similarities amongst each other, were found to be the most active. The selected fractions were tested for viability, proliferation and death induction on cultures of HL-60 promycloblastic leukemia cells. The results suggested that the observed cytotoxicity is related to apoptosis induction. (C) 2007 Elsevier Inc. All rights reserved.

Lercanidipine reduces matrix metalloproteinase-2 activity and reverses vascular dysfunction in renovascular hypertensive rats

Increased expression/activity of matrix metalloproteinases (MMPs), especially MMP-2, plays a role in the vascular alterations induced by hypertension, and increased oxidative stress is a major factor activating MMPs. Here, we hypothesized that lercanidipine, a calcium channel blocker, could attenuate the increases in oxidative stress and MMP-2 expression/activity in the two-kidney, one-clip (2K-1C) hypertensive rats. Sham-operated or 2K-1C hypertension rats were treated with lercanidipine 2.5 mg/kg/day (or vehicle) starting three weeks after hypertension was induced. Systolic blood pressure was monitored weekly. After five weeks of treatment, aortic rings were isolated to assess endothelium-dependent and independent relaxations. Quantitative morphometry of structural changes in the aortic wall were studied in hematoxylin/eosin sections. Aortic MMP-2 levels were determined by gelatin zymography. Aortic MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real-time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined using a fluorometric method. Lercanidipine attenuated 2K-1C hypertension (224 12 versus 183 11 mm Hg in 2K-1C rats and 2K-1C + Lercandipine rats, respectively; P < 0.01) and prevented the reduction in endothelium-dependent vasorelaxation found in 2K-1C rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of 2K-1C rats (all P < 0.05). Lercandipine attenuated 2K-1C-induced increases in MMP-2 by more than 60% and blunted 2K-1C-induced increases in oxidative stress (both P < 0.001). While hypertension-induced significant aortic wall hypertrophy and approximately 9-fold increases in the ratio of MMP-2MMP-2 mRNA expression (both P < 0.05), lercandipine did not affect these changes. These results suggest that lercanidipine produces antihypertensive effects and reverses the endothelial dysfunction associated with 2K-1C hypertension, probably through mechanisms involving antioxidant effects leading to lower MMP-2 activation. (C) 2008 Elsevier B.V. All rights reserved.

Antioxidant activity of flavonoids in isolated mitochondria

Mitochondria are important intracellular sources and targets of reactive oxygen species (ROS), while flavonoids, a large group of secondary plant metabolites, are important antioxidants. Following our previous study on the energetics of mitochondria exposed to the flavonoids quercetin, taxifolin, catechin and galangin, the present work addressed the antioxidant activity of these compounds (1-50 mu mol/L) on Fe2+/citrate-mediated membrane lipid peroxidation (LPO) in isolated rat liver mitochondria, running in parallel studies of their antioxidant activity in non-organelle systems. Only quercetin inhibited the respiratory chain of mitochondria and only galangin caused uncoupling. Quercetin and galangin were far more potent than taxifolin and catechin in affording protection against LPO (IC50 = 1.23 +/- 0.27 and 2.39 +/- 0.79 mu mol/L, respectively), although only quercetin was an effective scavenger of both 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals. These results, together with the previous study, suggest that the 2,3-double bond in conjugation with the 4-oxo function in the flavonoid structure are major determinants of the antioxidant activity of flavonoids in mitochondria, the presence of an o-di-OH structure on the B-ring, as occurs in quercetin, favours this activity via superoxide scavenging, while the absence of this structural feature in galangin, favours it via a decrease in membrane fluidity and/or mitochondrial uncoupling. Copyright (c) 2008 John Wiley & Sons, Ltd.

Mitochondrial function in the yeast form of the pathogenic fungus Paracoccidioides brasiliensis

Differences between the respiratory chain of the fungus Paracoccidioides brasiliensis and its mammalian host are reported. Respiration, membrane potential, and oxidative phosphorylation in mitochondria from P. brasiliensis spheroplasts were evaluated in situ, and the presence of a complete (Complex I-V) functional respiratory chain was demonstrated. In succinate-energized mitochondria, ADP induced a transition from resting to phosphorylating respiration. The presence of an alternative NADH-ubiquinone oxidoreductase was indicated by: (i) the ability to oxidize exogenous NADH and (ii) the lack of sensitivity to rotenone and presence of sensitivity to flavone. Malate/NAD(+)-supported respiration suggested the presence of either a mitochondrial pyridine transporter or a glyoxylate pathway contributing to NADH and/or succinate production. Partial sensitivity of NADH/succinate-supported respiration to antimycin A and cyanide, as well as sensitivity to benzohydroxamic acids, suggested the presence of an alternative oxidase in the yeast form of the fungus. An increase in activity and gene expression of the alternative NADH dehydrogenase throughout the yeast`s exponential growth phase was observed. This increase was coupled with a decrease in Complex I activity and gene expression of its subunit 6. These results support the existence of alternative respiratory chain pathways in addition to Complex I, as well as the utilization of NADH-linked substrates by P. brasiliensis. These specific components of the respiratory chain could be useful for further research and development of pharmacological agents against the fungus.

Crystal structure of Trypanosoma cruzi dihydroorotate dehydrogenase from Y strain

Trypanosoma cruzi is the etiological agent of Chagas` disease, a pathogenesis that affects millions of people in Latin America. Here, we report the crystal structure of dihydroorotate dehydrogenase (DHODH) from T cruzi strain Y solved at 2.2 angstrom resolution. DHODH is a flavin mononucleotide containing enzyme, which catalyses the oxidation Of L-dihydroorotate to orotate, the fourth step and only redox reaction in the de novo biosynthesis of pyrimidine nucleotides. Genetic studies have shown that DHODH is essential for T cruzi survival, validating the idea that this enzyme can be considered an attractive target for the development of antichagasic drugs. In our work, a detailed analysis of T cruzi DHODH crystal structure has allowed us to suggest potential sites to be further exploited for the design of highly specific inhibitors through the technology of structure-based drug design. (c) 2008 Elsevier Inc. All rights reserved.

Neuropharmacological effects in mice of Lychnophora species (Vernonieae, Asteraceae) and anticonvulsant activity of 4,5-di-O-[E]-caffeoylquinic acid isolated from the stem of L-rupestris and L-staavioides

Aiming at contributing with the search for neuroactive substances from natural sources, we report for the first time antinociceptive and anticonvulsant effects of some Lychnophora species. We verify the protective effects of polar extracts (600 mg/kg, intraperitoneally), and methanolic fractions of L. staavioides and L. rupestris (100 mg/kg, intraperitoneally) in pentylenetetrazole-induced seizures on mice. Previously, a screening was accomplished, evaluating the antinociceptive central activity (hot plate test), with different extracts of L. rupestris, L. staavioides and L. diamantinana. It was possible to select the possible extracts of Lychnophora with central nervous system activity. Some of the active extracts were submitted to fractionation and purification process and the methanolic fractions of L. rupestris (stem) and L. staavioides (stem), with anticonvulsant properties (100 mg/kg, intraperitoneally), yielded 4,5-di-O-[E]-caffeoylquinic acid. This substance was injected intraperitoneally in mice and showed anticonvulsant effect against pentylenetetrazole-induced seizures at doses of 25 and 50 mg/kg. It has often been shown that seizures induced by pentylenetetrazole are involved in inhibition and/or attenuation of GABAergic neurotransmission. However, other systems of the central nervous system such as adenosinergic and glutamatergic could be involved in the caffeoylquinic acid effects. Further studies should be conducted to verify that the target receptor could be participating in this anticonvulsant property. Although other investigations have reported a series of biological activities from Lychnophora species, this is the first report of central analgesic and anticonvulsant activity in species of this genus.