Francieli Moro Stefanello

Neuroprotective and antioxidant effects of curcumin in a ketamine-induced model of mania in rats

Bipolar disorder (BD) is a chronic and debilitating illness characterized by recurrent manic and depressive episodes. Our research investigates the protective effects of curcumin, the main curcuminoid of the Indian spice turmeric, in a model of mania induced by ketamine administration in rats. Our results indicated that ketamine treatment (25 mg/kg, for 8 days) induced hyperlocomotion in the open-field test and oxidative damage in prefrontal cortex (PFC) and hippocampus (HP), evaluated by increased lipid peroxidation and decreased total thiol content. Moreover, ketamine treatment reduced the activity of the antioxidant enzymes superoxide dismutase and catalase in the HP. Pretreatment of rats with curcumin (20 and 50 mg/kg, for 14 days) or with lithium chloride (45 mg/kg, positive control) prevented behavioral and pro-oxidant effects induced by ketamine. These findings suggest that curcumin might be a good compound for preventive intervention in BD, reducing the episode relapse and the oxidative damage associated with the manic phase of this disorder.

Antioxidant capacity and environmentally friendly synthesis of dihydropyrimidin-(2H)-ones promoted by naturally occurring organic acids

The Biginelli reaction is a multicomponent reaction involving the condensation between an aldehyde, a β‐ketoester, and urea or thiourea, in the presence of an acid catalyst, producing dihydropyrimidinones (DHPMs). Owing to their important pharmacological properties, the DHPMs have been studied by many authors. However, most of the methodologies used for the synthesis of these compounds require drastic reaction conditions. In the current study, we report an efficient and clean procedure for preparing DHPMs by the use of citric acid or tartaric acid as a promoter of the Biginelli synthesis in ethanol as solvent. In addition, we have evaluated the antioxidant capacity of the compounds synthesized by the 2,2‐diphenyl‐1‐picrylhydrazyl radical scavenging assay and the thiobarbituric acid‐reactive species test. Two compounds presented antioxidant activity and also reduced lipid peroxidation at concentrations of 200 and 300 µM. In summary, we report an environmentally friendly procedure for the preparation of DHPMs and demonstrate the antioxidant capacity of some of the compounds.

Cytotoxic and apoptotic effects of chalcone derivatives of 2-acetyl thiophene on human colon adenocarcinoma cells

Recent studies report that chalcones exhibit cytotoxicity to human cancer cell lines. Typically, the form of cell death induced by these compounds is apoptosis. In the context of the discovery of new anticancer agents and in light of the antitumour potential of several chalcone derivatives, in the present study, we synthesized and tested the cytotoxicity of six chalcone derivatives on human colon adenocarcinoma cells. Six derivatives of 3‐phenyl‐1‐(thiophen‐2‐yl) prop‐2‐en‐1‐one were prepared and characterized on the basis of their 1H and 13C NMR spectra. HT‐29 cells were treated with synthesized chalcones on two concentrations by three different incubation times. Cells were evaluated by cell morphology, Tetrazolium dye (MTT) colorimetric assay, live/dead, flow cytometry (annexin V) and gene expression analyses to determine the cytotoxic way. Chalcones 3‐(4‐bromophenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one (C06) and 3‐(2‐nitrophenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one (C09) demonstrated higher cytotoxicity than other chalcones as shown by cell morphology, live/dead and MTT assays. In addition, C06 induced apoptosis on flow cytometry annexin V assay. These data were confirmed by a decreased expression of anti‐apoptotic genes and increased pro‐apoptotic genes.

Role of antioxidants on Na(+),K (+)-ATPase activity and gene expression in cerebral cortex of hyperprolinemic rats.

Considering that Na+,K+-ATPase is an embedded-membrane enzyme and that experimental chronic hyperprolinemia decreases the activity of this enzyme in brain synaptic plasma membranes, the present study investigated the effect of chronic proline administration on thiobarbituric acid-reactive substances, as well as the influence of antioxidant vitamins E plus C on the effects mediated by proline on Na+,K+-ATPase activity in cerebral cortex of rats. The expression of Na+,K+-ATPase catalytic subunits was also evaluated. Results showed that proline increased thiobarbituric acid-reactive substances, suggesting an increase of lipid peroxidation. Furthermore, concomitant administration of vitamins E plus C significantly prevented the increase of lipid peroxidation, as well as the inhibition of Na+,K+-ATPase activity caused by proline. We did not observe any change in levels of Na+,K+-ATPase mRNA transcripts after chronic exposure to proline and vitamins E plus C. These findings provide insights into the mechanisms through which proline exerts its effects on brain function and suggest that treatment with antioxidants may be beneficial to treat neurological dysfunctions present in hyperprolinemic patients.

Eugenol derivatives as potential anti-oxidants: is phenolic hydroxyl necessary to obtain an effect?

Eugenol, obtained from clove oil (Eugenia caryophyllata), possess several biological activities. It is anti‐inflammatory, analgesic, anaesthesic, antipyretic, antiplatelet, anti‐anaphylactic, anticonvulsant, anti‐oxidant, antibacterial, antidepressant, antifungal and antiviral. The anti‐oxidant activity of eugenol have already been proven. From this perspective testing, a series of planned structural derivatives of eugenol were screened to perform structural optimization and consequent increase of the potency of these biological activities.

Antidepressant-like effects of aqueous extract from Cecropia pachystachya leaves in a mouse model of chronic unpredictable stress

Chronic stressful stimuli influence disease susceptibility to depression, cardiovascular, metabolic and neurodegenerative disorders. The present work investigated antidepressant and antioxidant properties of the aqueous extract from Cecropia pachystachya in a mouse model of chronic unpredictable stress (CUS). Our results indicated that acute administration of the aqueous extract (AE) from C. pachystachya (200 and 400mg/kg, p.o.) produced an antidepressant-like effect in the forced swimming test (FST). The chronic treatment with C. pachystachya extract (200mg/kg, p.o., for 14 days) prevented the depressant-like effect but not the anxiogenic effect induced by CUS. In addition to the behavioral modifications, the 14 days of CUS increased lipid peroxidation in the hippocampus (HP) and prefrontal cortex (PFC), decreased total thiol content and glutathione peroxidase activity in the HP. C. pachystachya AE administration during CUS protocol was able to prevent the oxidative damage induced by stress. However, no changes were observed in the activity of the antioxidant enzymes superoxide dismutase and catalase in the above cited brain areas after the stress protocol and treatment. Our results suggest that C. pachystachya prevented both depressive behavior and oxidative damage induced by CUS, supporting its neuroprotective potential against behavioral and biochemical dysfunctions induced by chronic stress.

Alterations of ectonucleotidases and acetylcholinesterase activities in lymphocytes of Down syndrome subjects: Relation with inflammatory parameters

BACKGROUND Subjects with Down syndrome (DS) have an increased susceptibility to infections and autoimmune disorders. ATP, adenosine, and acetylcholine contribute to the immune response regulation, and NTPDase, adenosine deaminase (ADA) and acetylcholinesterase (AChE) are important enzymes in the control of the extracellular levels of these molecules. We evaluated the activities of these enzymes and the cytokine levels in samples of DS individuals. METHODS The population consisted of 23 subjects with DS and 23 healthy subjects. Twelve milliliters of blood was obtained from each subject and used for lymphocyte and serum preparation. Lymphocytes were separated on Ficoll density gradients. After isolation, NTPDase and AChE activities were determined. RESULTS The NTPDase activity using ADP as substrate was increased in lymphocytes of DS patients compared to control (P<0.05); however, no alterations were observed in the ATP hydrolysis. An increase was observed in the AChE activity in lymphocytes and in ADA activity in serum of DS patients when compared to healthy subjects (P<0.05). In DS subjects, an increase in the levels of IL-1β, IL-6, TNF-α and IFN-γ and a decrease in the IL-10 levels were also observed (P<0.05). CONCLUSIONS Alterations in the NTPDase, ADA and AChE activities as well changes in the cytokine levels may contribute to immunological alterations observed in DS.

Green juice as a protector against reactive species in rats

INTRODUCTION Green juice is popularly known for introducing antioxidants, improving intestinal function and reducing weight gain. OBJECTIVES In the present study we determine the antioxidant effect of green juice comparing it with orange juice. METHODS Rats were divided into three experimental groups and submitted to supplementation for 15 days: the (GJ) group received green juice, the (OJ) group received orange juice and the control group received water. We evaluated the antioxidant activity and total phenolic content of green and orange juices, as well as rat weight gain. We also investigated some oxidative stress parameters, namely thiobarbituric acid-reactive substances (TBARS), superoxide dismutase and catalase in rat cerebral cortex. RESULTS AND DISCUSSION Results showed that GJ had significantly less weight gain than the control group. With respect to antioxidant activity screening, the remaining percentage of DPPH at dilutions 1:10, 1:100 and 1:1000 of green juice was 22.8%, 58% and 78%, and orange juice, at the same dilutions, was 5.6%, 5.6% and 77.2%, respectively. The ability of juices to reduce the ABTS radical was 3.5 mmol trolox/L for green juice and 5.2 mmol trolox/L for orange juice. Additionally, the green juice did not present any difference in total phenolic acid content when compared to orange juice. TBARS were reduced in GJ and OJ. Besides, GJ supplementation decreased catalase activity. In conclusion, our data showed that green juice reduced weight gain, lipoperoxidation and catalase activity, suggesting that this supplementation may have a protective effect against reactive species.

Efficient Synthesis and Antioxidant Evaluation of 2-Aryl-3-(Pyrimidin-2-yl)-Thiazolidinones

In the present study, we reported the efficient synthesis of 11 3‐(pyrimidin‐2‐yl)‐thiazolidinones in good yields using molecular sieve as the desiccant agent. In addition, we have evaluated the antioxidant capacity of the synthesized compounds by the 2,2‐diphenyl‐2‐picrylhydrazyl hydrate (DPPH•) and the 2,2‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) diammonium salt (ABTS+•) radicals scavenging assay. Six compounds showed antioxidant activity towards DPPH• (EC50 between 16.13 and 49.94 µg/mL) and also demonstrated excellent activity regarding ABTS+• (TEAC: 10.32–53.52). These results showed that compounds 3‐(pyrimidin‐2‐yl)‐thiazolidinones may be easily synthesized by a less expensive procedure and could be a good starting point to the development of new antioxidant compounds.

Vaccinium virgatum fruit extract as an important adjuvant in biochemical and behavioral alterations observed in animal model of metabolic syndrome

The aim of this study was to investigate the effect of blueberry (Vaccinium virgatum) fruit extract on metabolic, behavioral and oxidative stress parameters in the hippocampus and cerebral cortex of mice submitted to an experimental model of metabolic syndrome induced by a highly palatable diet (HPD). Mice C57BL/6 were divided into 4 experimental groups: (1) received standard chow and saline orally, (2) received standard chow and blueberry hydroalcoholic extract, (3) received HPD and saline orally, (4) received HPD and blueberry hydroalcoholic extract. The animals were treated for 150days. Our results showed that the animals fed with HPD presented insulin resistance, increased body weight, visceral fat, glucose, triglycerides, and total cholesterol when compared to the control group. The blueberry extract prevented the increase of these metabolic parameters. Also, the extract was able to reduce the levels of thiobarbituric acid reactive substances in the cerebral cortex and hippocampus of animals submitted to HPD. In contrast, no differences were observed in the total thiol content, activity of the antioxidant enzymes catalase and superoxide dismutase. In addition, the HPD fed animals showed a significant increase in immobility time in the forced swimming test and blueberry prevented this alteration, although no changes were observed in the ambulatory behavior, as well as in the anxiolytic profile of these animals. Overall, our findings suggest that chronic consumption of blueberry extract exhibits hypoglycemic, hypolipidemic, antidepressant-like and antiperoxidative effects in an animal model of metabolic syndrome.