Caroline Honaiser Lescano

Oxidative Stability of Baru (Dipteryx alata Vogel) Oil Monitored by Fluorescence and Absorption Spectroscopy

Baru (Dipteryx alata Vogel) is a native fruit of the Brazilian savanna that provides a nutritive oil, which also has medicinal properties. Baru fruits were collected in central-western Brazil, and the oil was obtained by pressing the seeds. The Baru oil was heated at 110°C for 24 h, and its oxidative stability was investigated by using fluorescence and absorption spectroscopy. The data showed that both absorption and fluorescence were able to precisely monitor the oil degradation induced by the thermooxidative process. The results revealed a rapid growth of the primary compounds generation in the first 16 hours of degradation. Significant amounts of secondary compounds began to be generated after 14 hours.

Campomanesia adamantium Peel Extract in Antidiarrheal Activity: The Ability of Inhibition of Heat-Stable Enterotoxin by Polyphenols

Campomanesia adamantium (Myrtaceae) is a medicinal plant distributed in Brazilian Cerrado. Different parts of this plant are used in popular medicine for treatment of several diseases like fever, diarrhea, hypercholesterolemia and rheumatism. The aim of this work was to evaluate the inhibition of heat-stable enterotoxin type A (STa) by gallic acid present in the peel of C. adamantium fruit and assays to assess the antidiarrheal activity, anti-inflammatory and cytotoxic properties of peel extract using the T84 cell line model. The possible inhibition exerted by the gallic acid of the peel extract on the STa peptide was inferred by molecular dynamics simulations. The antidiarrheal effects were investigated measuring cGMP accumulation in cells after stimulation by STa toxin and antibacterial activity was assessed. The anti-inflammatory activity was assessed by inhibition of COX-1 and COX-2. MTT and LDH assays were used to evaluate any possible cytotoxic action while the CyQUANT test was used to investigate the effect on cell proliferation. A representation showing how the possible interactions between STa and the gallic acid of the extract might reduce the action of the enterotoxin is presented. C. adamantium peel extract significantly decreased the levels of cGMP in T84 cells. However, no effect on the species of microorganisms was observed. The extract also inhibited COX-1 (IC50 255.70 ± 0.04 ng/mL) and COX-2 (IC50 569.50 ± 0.11 ng/mL) enzymes. Cytotoxicity assay have shown significant changes in cells treated with the extract, which inhibited the cell proliferation until 72 hours of treatment. Direct interactions of phenolic compounds present in the extract with the STa toxin may limit its activity. Curative effect in the diarrhea treatment and its anti-inflammatory action is based on the pharmacological properties, mechanism of action of the C. adamantium peel extract, and no toxic effects of the peel extract presented on this work.

Study on the Cytotoxic, Genotoxic and Clastogenic Potential of Attalea phalerata Mart. ex Spreng. Oil Pulp In Vitro and In Vivo Experimental Models

Attalea phalerata Mart. ex Spreng. (Arecaceae), popularly known as “bacuri”, is used in Brazilian folk medicine. Its oil is used orally to relieve pulmonary congestion and joint pain. In topical applications, it is applied as an effective hair tonic and anti-dandruff. The in natura pulp and its nuts are used as food because of its nutritional value. Despite its use in folk medicine, there is a lack of data regarding its in vivo/in vitro cytotoxic/genotoxic and clastogenic effects. Therefore, in this study, we evaluated the cytotoxic, genotoxic and clastogenic effects of Attalea phalerata Mart. ex Spreng. oil (APMO) in vitro and in vivo. For the analysis of cytotoxic potential, the Artemia salina and MTT (3-(4,5-dimethizzol-zyl)-2,5-diphenyltetrazolium bromide) assays were performed. Possible cytotoxic, genotoxic and clastogenic effects of APMO intake were determined by performing the comet and micronucleus assays. Male and female Wistar rats were orally treated with doses of 125, 250, 500 or 1000 mg.kg-1 of the APMO daily for 28 consecutive days (four weeks). The results showed that the APMO did not induce cell death in the experiments of Artemia salina and MTT, indicating that it has no cytotoxicity. The APMO did not cause significant damage to the DNA of the rats in the four doses used when compared to the negative control group (saline + Tween® 80). The APMO did not present any significant increase in micronucleated polychromatic erythrocytes (MNPCEs) for the four tested doses. When compared to the positive control group, all groups (comet and micronucleus tests) were statistically different. These data suggest that the administration of Attalea phalerata Mart oil. ex Spreng does not cause cytotoxicity, genotoxicity and clastogenicity in experimental models in vitro and in vivo following oral administration in this study.

Anti-inflammatory, antiproliferative and cytoprotective potential of the Attalea phalerata Mart. ex Spreng. pulp oil

The anti-inflammatory, antiproliferative and cytoprotective activity of the Attalea phalerata Mart. ex Spreng pulp oil was evaluated by in vitro and in vivo methods. As for the chemical profile, the antioxidant activity was performed by spectrophotometry, and the profile of carotenoids and amino acids by chromatography. Our data demonstrated that A. phalerata oil has high carotenoid content, antioxidant activity and the presence of 5 essential amino acids. In the in vitro models of inflammation, the oil demonstrated the capacity to inhibit COX1 and COX2 enzymes, the production of nitric oxide and also induces macrophages to spreading. In the in vivo models of inflammation, the oil inhibited edema and leukocyte migration in the Wistar rats. In the in vitro model of antiproliferative and cytoprotective activity, the oil was shown inactive against the kidney carcinoma and prostate carcinoma lineage cells and with cytoprotective capacity in murine fibroblast cells, inhibiting the cytotoxic action of doxorubicin. Therefore, it is concluded that A. phalerata pulp oil has anti-inflammatory effects with nutraceutical properties potential due to the rich composition. Moreover, the oil also has cytoprotective activity probably because of its ability to inhibit the action of free radicals.

Nutritional and chemical characterizations of fruits obtained from Syagrus romanzoffiana, Attalea dubia, Attalea phalerata and mauritia flexuosa

Several species of Arecaceae are widely distributed in tropical regions and are economically important as a source of vegetable oil and bioactive nutrients beneficial to health and human nutrition. In this work, the physical and chemical characteristics of the oils and fruits from Syagrus romanzoffiana, Attalea phalerata, Mauritia flexuosa and for the first time for Attalea dubia (Mart.) Burret were determined. All fruits were dimensioned according to the biometric analysis (size and mass). Nutritional analysis showed high levels of lipids, proteins, sugars and fibers, as well as Ca, Mg, K, Cu, Mn, Fe and Zn minerals. The composition of fatty acids showed the predominance of short and unsaturated fatty acids carbon chain. All fruits presented high content of polyphenols and carotenoids (except for S. romanzoffiana). Moreover, all fruits demonstrate antioxidant activity by direct capture of free radicals ABTS and DPPH. Finally, our results demonstrate that these fruits have a relevant concentration of nutrients and bioactive compounds with importance for human health. Such data open up promising prospects for the scientific exploration and use of these fruits as an alternative source to combat malnutrition as well as to compose formulations of food products with functional properties. Finally, our results demonstrate that these fruits present a relevant concentration of nutrients and bioactive compounds with importance for human health, with promising perspectives for the scientific exploration and use of these fruits as an alternative source to avoid malnutrition as well as to compose formulations of food products with functional properties.

Effect of Polyphenols From Campomanesia adamantium on Platelet Aggregation and Inhibition of Cyclooxygenases: Molecular Docking and in Vitro Analysis

Campomanesia adamantium is a medicinal plant of the Brazilian Cerrado. Different parts of its fruits are used in popular medicine to treat gastrointestinal disorders, rheumatism, urinary tract infections and inflammations. Despite its widespread use by the local population, the mechanisms involving platelet aggregation and the inhibition of cyclooxygenase by C. adamantium are unknown. This study evaluated the chemical composition, antioxidant activities and potential benefits of the C. adamantium peel extract (CAPE) and its components in the platelet aggregation induced by arachidonic acid in platelet-rich plasma. Aspects of the pharmacological mechanism were investigated as follows: platelet viability, calcium mobilization, levels of the cyclic nucleotides cAMP and cGMP, thromboxane B2 levels, and the inhibitory effects on COX-1 and COX-2 were studied in vitro and using molecular docking in the catalytic domain of these proteins. The major CAPE constituents standing out from the chemical analysis are the flavonoids, namely those of the flavones and chalcones class. The results showed that CAPE, quercetin and myricetin significantly decreased arachidonic acid-induced platelet aggregation; the assays showed that CAPE and quercetin decreased the mobilization of calcium and thromboxane B2 levels in platelets and increased cAMP and cGMP levels. Moreover, CAPE inhibited the activity of COX-1 and COX-2, highlighting that quercetin could potentially prevent the access of arachidonic acid more to the catalytic site of COX-1 than COX-2. These results highlight CAPE’s potential as a promising therapeutic candidate for the prevention and treatment of diseases associated with platelet aggregation.

Mirabegron, a β 3 -adrenoceptor agonist reduced platelet aggregation through cyclic adenosine monophosphate accumulation

&NA; Mirabegron is a &bgr;3‐adrenoceptor agonist and released on the marked for the treatment of overactive bladder. Because mirabegron is the only &bgr;3‐adrenoceptor agonist available and substances that increase the levels of cyclic adenosine monophosphate (cAMP) inhibit platelet activity, we tested the hypothesis that mirabegron could have antiplatelet activity. Collagen‐ and thrombin induced platelet aggregation, thromboxane B2 (TXB2) and cyclic nucleotides quantification and calcium (Ca2+) mobilization were determined in the absence and presence of mirabegron in human washed platelets. Our results revealed that mirabegron (10−300 &mgr;M) produced significant inhibitions on platelet aggregation induced by collagen‐ or thrombin, accompanied by greater intracellular levels of cAMP. The &bgr;3‐adrenoceptor antagonist L 748,337 (1 &mgr;M) and the adenylate cyclase inhibitor, SQ 22,536 (100 &mgr;M) reversed the inhibition induced by mirabegron in thrombin‐stimulated platelets. The selective antagonists for &bgr;1‐and &bgr;2‐adrenoceptors, atenolol and ICI 117,551 (3 &mgr;M), respectively did not interfere on the inhibition induced by mirabegron. In Fluo‐4 loaded platelets, mirabegron reduced the total and intracellular Ca2+ levels. Pre‐incubation with mirabegron almost abolished the levels of TXB2. Mirabegron did not augment the intracellular levels of cyclic guanosine monophosphate. In conclusion, mirabegron inhibited human platelet aggregation through cAMP accumulation, thus suggesting that substances that activate &bgr;3‐adrenoceptor could be beneficial as adjuvant antiplatelet therapy.

Cytotoxic, genotoxic and mutagenic evaluation of Alibertia edulis (rich.) a. Rich. ex DC: an indigenous species from Brazil

Abstract Tea leaves of Alibertia edulis is popularly used in folk medicine. However, studies on the genotoxicity of this plant are not available. We aimed to investigate the in vivo and in vitro cytotoxic, genotoxic and mutagenic potentials of the aqueous extract of A. edulis leaves (AEAE). Antioxidant assays, the Artemia salina test, MTT in human platelets, micronucleus in bone marrow and comet in peripheral blood were performed. Animals received four different doses of the AEAE by oral gavage for 30 days. Saline and cyclophosphamide were used as controls. The AEAE exhibited a maximal inhibition at 100 and 250 µg/mL, according to the ABTS and DPPH methods, respectively. The A. salina assay showed that the AEAE presented some toxicity at doses of 100, 250 and 500 μg/mL. Through the MTT assay, the AEAE showed no toxic effects on human platelets during the incubation period. The alkaline comet assay showed that all doses of the AEAE were statistically similar to the negative control group since they did not induce any significant increase of the overall number of damaged cells nor the severity of the cell damage. In the micronucleous assay, results demonstrate that the AEAE did not increase the production of micronucleated polychromatic erythrocytes and was statistically similar to the negative control. The four doses of the plant extract did not affect the production of new erythrocytes and were statistically similar to the negative control groups. Furthermore, the AEAE demonstrated no cytotoxicity, genotoxicity and mutagenicity at the doses tested in rats.

Activation of soluble guanylyl cyclase with inhibition of multidrug resistance protein inhibitor-4 (MRP4) as a new antiplatelet therapy

Graphical abstract Figure. No Caption available. ABSTRACT The intracellular levels of cyclic GMP are controlled by its rate of formation through nitric oxide‐mediated stimulation of soluble guanylate cyclase (sGC) and its degradation by phosphodiesterases. Multidrug resistance protein 4 (MRP4) expressed in human platelets pumps cyclic nucleotides out of cells. In search for new antiplatelet strategies, we tested the hypothesis that sGC activation concomitant with MRP4 inhibition confers higher antiplatelet efficacy compared with monotherapy alone. This study was undertaken to investigate the pharmacological association of the sGC activator BAY 60‐2770 with the MRP4 inhibitor MK571 on human washed platelets. Collagen‐ and thrombin‐induced platelet aggregation and ATP‐release reaction assays were performed. BAY 60‐2770 (0.001–10 &mgr;M) produced significant inhibitions of agonist‐induced platelet aggregation accompanied by reduced ATP‐release. Pre‐incubation with 10 &mgr;M MK571 alone had no significant effect on platelet aggregation and ATP release, but it produced a left displacement by about of 10–100‐fold in the concentration‐response curves to BAY 60‐2770. Pre‐incubation with MK571increased and decreased, respectively, the intracellular and extracellular levels of cGMP to BAY 60‐2770, whereas the cAMP levels remained unchanged. The increased VASP‐serine 239 phosphorylation in BAY 60‐2770‐treated platelets was enhanced by MK571. In Fluo‐4‐loaded platelets, BAY 60‐2770 reduced the intracellular Ca2+ levels, an effect significantly potentiated by MK571. Flow cytometry assays showed that BAY 60‐2770 reduces the &agr;IIb&bgr;3 integrin activation, which was further reduced by MK571 association. Blocking the MRP4‐mediated efflux of cGMP may be a potential mechanism to enhance the antiplatelet efficacy of sGC activators.

Corrigendum to “Oxidative Stability of Baru (Dipteryx alata Vogel) Oil Monitored by Fluorescence and Absorption Spectroscopy”

Baru (Dipteryx alataVogel) is a native fruit of the Brazilian savanna that provides a nutritive oil, which also hasmedicinal properties. Baru fruits were collected in central-western Brazil, and the oil was obtained by pressing the seeds.The Baru oil was heated at 110C for 24 h, and its oxidative stability was investigated by using fluorescence and absorption spectroscopy. The data showed that both absorption and fluorescence were able to precisely monitor the oil degradation induced by the thermooxidative process.The results revealed a rapid growth of the primary compounds generation in the first 16 hours of degradation. Significant amounts of secondary compounds began to be generated after 14 hours.