Naltrexone/bupropion modifies weight, food intake, and Drd2 gene expression in rats.

Obesogenic diets are known to induce obesity and changes in food intake in experimental animals. Obesity negatively affects the peripheral metabolism and neural aspects, such as changes in eating behavior. In obese animals, dopamine (DA) receptor levels are reduced. DA is one of the main peptides involved in the motivation and pleasure of eating. A combination of naltrexone/bupropion (NB) has shown promise in controlling metabolic alterations, but there are few studies on how they modulate dopaminergic expression. NB, in addition to reducing food intake and body weight, can modify tyrosine hydroxylase (Th) and DA receptor D2 (Drd2) levels in the mesolimbic areas of rats submitted to a high-fat diet (HF). The study evaluated the effect of NB on food intake, body weight, and expression levels of Th, Drd1a, and Drd2, in the nucleus accumbens and striatum of rats fed on HF diet. Wistar rats were grouped according to diet: standard (n = 20) and HF diet (n = 20). The food intake and body weight were analyzed. The gene expression of Th, Drd1a, and Drd2 was evaluated using real-time PCR. NB combination of 1 mg/kg and 20 mg/kg reduced food intake and body weight, increased Drd2 expression in rats on HF diet, and increased Th in rats on both experimental diets. The level of Drd1a was unchanged. We concluded that bodyweight reduction may be associated with decreased food intake in response to the increased Drd2 expression in the mesolimbic areas of rats that received an HF diet.

Characterization of a lignin from Crataeva tapia leaves and potential applications in medicinal and cosmetic formulations.

Lignins are phenolic macromolecules that have several applications. In this work, we examine some biological activities of a lignin-like macromolecule isolated from the Crataeva tapia leaves, not yet studied to evaluate its potential applications in medicinal and cosmetic formulations. Lignin was obtained by alkaline delignification and its physical-chemical characterization was made by means of FT-IR, UV-Vis, NMR spectroscopy, elementary analysis, molecular mass determination and thermal analysis. Lignin is of the GSH type, with levels of hydrogen (5.10%), oxygen (27.18%), carbon (67.60%), nitrogen (0.12%) and phenolic content of 189.6 ± 9.6 mg GAE/g. In addition, it is a thermally stable macromolecule with low antioxidant activity. Cytotoxicity and cytokine production were assessed by flow cytometry. The photoprotective activity was evaluated by adding different concentrations of lignin to a commercial cream. Lignin was not cytotoxic, it stimulated the production of TNF-α, IL-6 and IL-10 and did not promote a significant change in nitric oxide levels. In addition, this macromolecule was able to promote increased absorption of ultraviolet light from a commercial cream. These results reinforce the ethnopharmacological use of C. tapia leaves and suggest the need for further studies to determine the potential medicinal and cosmetic applications (sunscreen) of lignin from C. tapia leaves.

Toxicity assessment of saline extract and lectin-rich fraction from Microgramma vacciniifolia rhizome.

Microgramma vacciniifolia is broadly used in folk medicine but safety information is unavailable. Therefore, we evaluated the toxicity of a saline extract and a lectin-rich fraction of M. vacciniifolia rhizome. The extract showed hemolytic activity on mice erythrocytes at 1000 µg/mL, whereas the fraction promoted hemolysis (8.57-26.15%) at all tested concentrations (10-1000 µg/mL). Acute toxicity test in mice indicated an LD50 of >5000 mg/kg. Hematological alterations and increased serum alkaline phosphatase level were observed in the treated animals. Transaminases and urea levels increased in the groups treated with the extract or fraction at 5000 mg/kg. Leukocyte infiltration was observed in the liver of extract-treated animals and in the liver and lungs of mice treated with the fraction. The kidneys of animals treated with the fraction at 5000 mg/kg presented hydropic degeneration. The extract and fraction did not induce oxidative stress in the liver and did not show genotoxicity, as examined by micronucleus and comet assays. In conclusion, the preparations were not lethal to mice but caused some signs of toxicity, mainly the fraction. The results indicated the need to evaluate the toxicity of M. vacciniifolia rhizome in other models and in chronic assays.

Correction: MOF@activated carbon: a new material for adsorption of aldicarb in biological systems.

Correction for 'MOF@activated carbon: a new material for adsorption of aldicarb in biological systems' by Carlos Alberto Fernandes de Oliveira et al., Chem. Commun., 2013, 49, 6486-6488.

Anacardic Acids from Cashew Nuts Prevent Behavioral Changes and Oxidative Stress Induced by Rotenone in a Rat Model of Parkinson's Disease.

Anacardic acids (AAs) are alkyl phenols mainly presenting in cashew nuts. The antioxidant effects of these compounds have been an area of interest in recent research, with findings suggesting potential therapeutic use for certain diseases. Nevertheless, none of these studies were performed in order to test the hypothesis of whether anacardic acids are capable of preventing behavioral changes and oxidative stress induced by the pesticide rotenone in experimental model of Parkinson's disease. In our research, adult male rats were treated orally with AAs (1, 3, 10, 25, 50, or 100 mg/kg/day) 1 h before rotenone (3 mg/kg; s.c.) for five consecutive days. The behavioral testing strategies, including tests for general locomotor activity (open field), motor coordination (rotarod), and spatial memory performance (elevated T-maze), were carried out. Lipoperoxidation levels and total superoxide dismutase (t-SOD) activity, as well as cytoplasmic and mitochondrial SOD gene expression, were assessed in the substantia nigra (SN), striatum, and cerebral cortex. The results showed that AAs dose-dependently prevented the rotenone-induced learning and motor impairment from 10 mg/kg/day. AAs also precluded rotenone-induced lipoperoxidation in all doses, acting directly on the mitochondria, and improved the t-SOD activity in the doses 25-100 mg/kg/day. AAs per se (100 mg/kg/day) increased SOD gene expression and t-SOD activity. Our findings indicate that the oral administration of AAs prevents rotenone-induced behavioral changes and oxidative stress, in part due to a modulatory action on the mitochondria and SOD gene expression. These data suggest that AAs have promising neuroprotective action against degenerative changes in Parkinson's disease.

Toxicological evaluation of essential oil from the leaves of Croton tetradenius (Euphorbiaceae) on Aedes aegypti and Mus musculus.

For control of Aedes aegypti, the main vector of dengue, botanical insecticides can be a viable alternative. Herein, we evaluated the chemical composition and insecticidal activity of the essential oils of the leaves of Croton tetradenius on Ae. aegypti larvae and adults. We also evaluated the acute toxicity in Mus musculus. The essential oil chemical analysis was performed using chromatography coupled with mass spectrometry and flame ionization detection. Female mice were used for assessing toxicity according to the Organization for Economic Cooperation and Development's Test Guideline 423/2001. Doses administered to mice orally and intraperitoneally were 5, 50, 300, and 2000 mg kg(-1). There was a greater toxic effect on larvae (LC50 = 0.152 mg mL(-1) and LC90 = 0.297 mg mL(-1)) and on adults (LC50 = 1.842 mg mL(-1) and LC90 = 3.156 mg mL(-1)) of Ae. aegypti after 24 h of exposure, when compared to other periods of exposure. Chemical analysis revealed 26 components, with camphor (25.49 %) as the major component. The acute toxicity via the intraperitoneal route identified an LD50 = 200 mg kg(-1) and by the oral route an LD50 = 500 mg kg(-1). Thus, the essential oil of C. tetradenius presents insecticidal potential for Ae. aegypti and has high safety threshold at the concentrations evaluated in this study.

Evaluation of Toxicity and Antimicrobial Activity of an Ethanolic Extract from Leaves of Morus alba L. (Moraceae).

This work evaluated an ethanolic extract from Morus alba leaves for toxicity to Artemia salina, oral toxicity to mice, and antimicrobial activity. Phytochemical analysis revealed the presence of coumarins, flavonoids, tannins, and triterpenes in the extract, which did not show toxicity to A. salina nauplii. No mortality and behavioral alterations were detected for mice treated with the extract (300 and 2000 mg/kg b.w.) for 14 days. However, animals that received the highest dose showed reduced MCV and MCHC as well as increased serum alkaline phosphatase activity. In treatments with the extract at both 300 and 2000 mg/kg, there was a reduction in number of leukocytes, with decrease in percentage of lymphocytes and increase in proportion of segmented cells. Histopathological analysis of organs from mice treated with the extract at 2000 mg/kg revealed turgidity of contorted tubules in kidneys, presence of leukocyte infiltration around the liver centrilobular vein, and high dispersion of the spleen white pulp. The extract showed antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, Candida krusei, Candida tropicalis, and Aspergillus flavus. In conclusion, the extract contains antimicrobial agents and was not lethal for mice when ingested; however, its use requires caution because it promoted biochemical, hematological, and histopathological alterations.

Evaluation of antioxidant and antiangiogenic properties of caesalpinia echinata extracts.

Natural products contain important combinations of ingredients, which may to some extent help to modulate the effects produced by oxidation substrates in biological systems. It is known that substances capable of modulating the action of these oxidants on tissue may be important allies in the control of neovascularization in pathological processes. The aim of this study was to evaluate the antioxidant and antiangiogenic properties of an ethanol extract of Caesalpinia echinata. The evaluation of antioxidant properties was tested using two methods (DPPH inhibition and sequestration of nitric oxide). The antiangiogenic properties were evaluated using the inflammatory angiogenesis model in the corneas of rats. The extract of C. echinata demonstrated a high capacity to inhibit free radicals, with IC50 equal to 42.404 µg/mL for the DPPH test and 234.2 µg/mL for nitric oxide. Moreover, it showed itself capable of inhibiting the inflammatory angiogenic response by 77.49%. These data suggest that biochemical components belonging to the extract of C. echinata interfere in mechanisms that control the angiogenic process, mediated by substrates belonging to the arachidonic acid cascade, although the data described above also suggest that the NO buffer may contribute to some extent to the reduction in the angiogenic response.

MOF@activated carbon: a new material for adsorption of aldicarb in biological systems.

A new composite was synthesized by the hydrothermal method using a 3D coordination network [Ln2(C4H4O4)3(H2O)2]·H2O (Ln = Eu and Tb) and activated carbon. The coordination network is formed within the pores of the charcoal, allowing for the use of this material as a detoxifying agent.

Atividade antifúngica e cinética de morte microbiana de extratos obtidos de Streptomyces spp. isolados de solos paraibanos / Antifungal activity and kinetics of microbial death of extracts obtained from Streptomyces spp. isolated from paraibano soils

Foram coletadas sessenta e oito amostras em diferentes solos paraibanos, com o isolamento de quarenta e nove cepas de Streptomyces spp. Após triagem antimicrobiana, por meio da técnica de difusão em meio sólido com blocos de agar, foram preparados os extratos dos microrganismos produtores de metabólitos bioativos, respectivamente cepas SP1 e SP3, e em seguida avaliados quanto a atividade antifúngica frente a espécies de fungos filamentosos de origem clínica e ATCC. O antagonismo foi determinado através dos ensaios de difusão com discos em meio sólido, microdiluição e cinética de morte microbiana. Os halos de inibição obtidos a partir dos extratos Sp-1 e Sp-3 apresentaram efeito antagônico com valores superiores aos halos de inibição promovidos pela droga controle, frequentemente utilizada na terapêutica antifúngica. Os resultados das concentrações inibitórias mínimas na microdiluição foram expressivos com valores fungicidas variando entre 10 mg e 0,078125 mg. Na cinética de morte microbiana, as atividades dos extratos Sp-1 e Sp-3 resultaram em dados estatisticamente significativos frente às cepas testes.

Sixty eight samples were collected in different soils of Paraiba, with the isolation of forty nine strains of Streptomyces spp. After screening antimicrobial followed the method of diffusion in solid medium with agar block, the extracts were prepared from microorganism producers of bioactive metabolites, respectively strains SP1 and SP3, and then evaluated for antifungal activity against strains of filamentous fungi of clinical origin and ATCC. The antagonism was determined through testing of diffusion disc in solid medium, microdilution and kinetics of microbial death. The inhibition zones obtained from extracts of Sp-1 and Sp-3 showed antagonistic effect with values greater than the halos of inhibition promoted by the drug control, often used in antifungal therapy. The results of minimum inhibitory concentrations in microdilution were significant with fungicide values ranging between 10 mg and 0.078125 mg. In the kinetics of microbial death, the activities of the extracts Sp-1 and Sp-3 resulted in statistically significant data front of strains tested.

Indigofera suffruticosa: an alternative anticancer therapy.

Indigofera suffruticosa Mill (Fabeceae) occurs in the Northeast countryside and has intensive popular use in the treatment of infectious, inflammatory and other processes. The main aim of the present work was to investigate the cytotoxic and antitumor effects of aqueous extracts of leaves of I. suffruticosa obtained by infusion and maceration as well as to evaluate the toxicological properties. Aqueous extracts did not exhibit cytotoxicity against HEp-2 (human epidermoid cancer cell) cell lines by MTT method. From the aqueous extract by infusion, the toxicological assay showed low order of toxicity. The antitumor effect of aqueous extracts by infusion (64.53%) and maceration (62.62%) against sarcoma 180 in mice at a dose of 50 mg kg(-1) (intraperitoneally), based on low order of toxicity was comparable to the control group, which showed 100% development. Considering the low order of toxicity and that it is highly effective in inhibiting growth of solid tumors, the aqueous extracts of leaves of I. suffruticosa may be used as an alternative anticancer agent.

Toxicological screening of Euphorbia tirucalli L.: developmental toxicity studies in rats.

Euphorbia tirucalli (Euphorbiaceae family), an environmental risk factor for Burkitt's lymphoma, also presents pharmacological activities. In the northeast region of Brazil its latex is used as an antimicrobial, antiparasitic in the treatment of coughs, rheumatism, cancer and other maladies as folk remedy. The present work concerns its developmental toxicity in rats. Wistar rats on the first day post-coitum (dpc) were grouped as control (distilled water) and treated (latex aqueous solution) groups. Animals were treated by oral gavage from the 1st to the 4th (Experiment I) and from the 5th to 7th dpc (Experiment II) and killed on the 5th or 14th dpc, respectively. Maternal variables were: clinical signs of toxicity, body weight, ovaries, liver and kidneys weight and number of corpora lutea. The uterine tubes and cornua were washed for counting and identification of embryos. The embryos and placenta were weighed. Apart from the leucopenia and the higher placental weight observed in treated rats from Experiment II, there were no significant differences between the groups. It is possible to conclude that the latex aqueous solution of Euphorbia tirucalli did not interfere with tubaric embryo development or with implantation, but it seems to alter the placenta morphology.

Synthesis of aminoacyl thiaolidones as potential antitumour agents.

In the scope of a research program aiming to perform the synthesis and pharmacological evaluation of novel possible antitumour prototype compounds, we report in this paper the synthesis of new peptidyl derivatives from 4-thiazolidone nucleus. The synthesis reactions have been performed based in peptide synthesis as strategies. The characterisation of this new class of compounds was performed with IR and (1)H-NMR spectroscopy. In vivo, antitumour activity tests showed that some of these compounds were able to inhibit significantly sarcoma S-180 tumour growth in mice, revealing itself as a new potential class of drugs in cancer chemotherapy.