Patricia Fernandes | Universidade Federal do Rio de Janeiro (UFRJ) (original) (raw)

Papers by Patricia Fernandes

European Journal of Cell Biology

We have investigated the relationship between peritoneal murine macrophage cytoskeleton and nitri... more We have investigated the relationship between peritoneal murine macrophage cytoskeleton and nitric oxide (NO) synthase (NOS). Activation of the cells with lipopolysaccharide plus interferon-gamma (LI) induced iNOS, detected by nitrite or by labeled L-citrulline production and by a specific antibody against macrophage iNOS. Addition of cytochalasin B (a microfilament-depolymerizing agent) caused a dose-dependent inhibition in NO production by macrophages, whereas colchicine (a microtubule depolymerizing agent) inhibited it only by 20% and not dose-dependently. Addition of cytochalasin B together with LI abolished nitrite and L-citrulline accumulation as well as the amount of iNOS antigen in activated macrophage. Moreover, addition of cytochalasin B 6 or 12 h after stimulus, also decreased the nitrite and L-citrulline production by macrophages although iNOS antigen content by Western blot was the same in the presence or in the absence of cytochalasin B added 12 h after activation. Since cytochalasin B failed to inhibit iNOS activity directly, its inhibitory effects on NO production by macrophages is likely to be indirect, through microfilament network in central regions of cells, but not in filaments seen at pseudopodia or edging processes. Our findings demonstrate that disruption of microfilaments but not of microtubules prevents the iNOS induction process and inhibits its enzymatic activity in activated macrophages.

ChemMedChem, 2015

Inhibitor of nuclear factor κB kinase 2 (IKK2) is suggested to be a potential target for the deve... more Inhibitor of nuclear factor κB kinase 2 (IKK2) is suggested to be a potential target for the development of novel anti-inflammatory and anticancer drugs. In this work, we applied structure-based drug design to improve the potency of the inhibitor (E)-N'-(4-nitrobenzylidene)-2-naphthohydrazide (LASSBio-1524, 1 a: IC50 =20 μM). The molecular model built for IKK2 together with the docking methodology employed were able to provide important and consistent information with respect to the structural and chemical inhibitor characteristics that may confer potency to IKK2 inhibitors, providing important guidelines for the development of a new N-acylhydrazone (NAH) derivative. (E)-N'-(4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzylidene)-2-naphthohydrazide hydrochloride (LASSBio-1829 hydrochloride, 10) is a 7-azaindole NAH able to inhibit IKK2 with an IC50 value of 3.8 μM. LASSBio-1829 hydrochloride was found to be active in several pharmacological inflammation tests in vivo, showing its potential as an anti-inflammatory prototype.

Effects of a nanocomposite containing Orbignya speciosa lipophilic extract on Benign Prostatic Hy... more Effects of a nanocomposite containing Orbignya speciosa lipophilic extract on Benign Prostatic Hyperplasia.

Cocos nucifera cultivated in Brazil is known as &... more Cocos nucifera cultivated in Brazil is known as "coco-da-Bahia" or "coqueiro-da-India". The tea from the husk fiber is widely used to several inflammatory disorders. Crude extract and fractions obtained from Cocos nucifera "common variety" were evaluated to test the anti-inflammatory and antinociceptive activities. Crude extract (CE, 50, 100, and 150 mg/kg), fraction 1 (F1, molecular weight lesser than 1 kDa, 1, 10, and 50mg/kg), fraction 2 (F2, molecular weight higher than 1 kDa, 1, 10, and 50mg/kg), and the references drugs morphine (5mg/kg), acetilsalicilic acid (200mg/kg), prometazine (30 mg/kg), and metisergide (5mg/kg) were evaluated on models of analgesia and inflammation. CE, F1, and F2 significantly develop peripheral and central antinociceptive activity but with less effect on supra-spinal regions of the brain. Administration of the opioid antagonist, naloxone (5mg/kg) inhibited the antinociceptive effect indicating that Cocos nucifera crude extract and fractions may be acting in opioid receptors. CE and F1 also inhibited rat paw edema induced by histamine, and serotonin. results demonstrated that Cocos nucifera and its fractions have antinociceptive and anti-inflammatory activities which confirm the popular use of this plant in several inflammatory disorders.

International Journal of Molecular Medicine, 2000

We studied the kinetics of in vivo nitrite production in the inflammatory reaction induced by M. ... more We studied the kinetics of in vivo nitrite production in the inflammatory reaction induced by M. bovis BCG into the pleural space. Pleural macrophages harvested from C57Bl/6 mice after acute BCG infection produced high levels of nitric oxide (NO). Enhanced production was obtained upon stimulation with LPS plus IFN-gamma. In sharp contrast, macrophages from DBA-2 mice produced low levels of NO, as nitrite, at the same time interval (24 h after BCG infection), being completely refractory to further stimulation. After the third day, NO production was similar in both strains. There was a close relationship between nitrite levels in the pleural exudate in vivo and those produced by harvested macrophages in vitro. In this in vivo system, the pattern of NO production by pleural macrophages one day after BCG infection was discrepant and unexpected in the response of C57Bl/6 and DBA-2 mice. However, this early response did not affect the late progressive NO production in both mice strains, that may be responsible to the late control of the mycobacteria growth.

Revista Brasileira de Farmacognosia, 2003

Araújo H.M.; Riveros-Moreno, V.; Assreuy J. Depolymerisation of macrophage filaments prevents ind... more Araújo H.M.; Riveros-Moreno, V.; Assreuy J. Depolymerisation of macrophage filaments prevents induction and inhibits activity of nitric oxide synthase.

Revista Brasileira de Farmacognosia, 2005

Revista Brasileira de Farmacognosia Brazilian Journal of Pharmacognosy 15(4): 310-315, Out./Dez. ... more Revista Brasileira de Farmacognosia Brazilian Journal of Pharmacognosy 15(4): 310-315, Out./Dez. 2005 RESUMO: Polygala paniculata L. (Polygalaceae) é uma erva que ocorre em todas as regiões do Brasil. No presente trabalho, foram avaliadas as atividades analgésica, através do teste da placa quente, da retirada de cauda e da formalina, e antiedematogênica, através do teste do edema de orelha induzido por óleo de cróton, dos extratos etanólicos obtidos das partes aéreas de Polygala paniculata selvagem e cultivadas por micropropagação. A aplicação oral do extrato etanólico de Polygala paniculata apresentou atividade analgésica, em ratos, tanto em testes de dor induzida por agentes térmicos (testes da placa quente e de retirada da cauda) quanto por agentes químicos (teste da formalina), de modo que os melhores resultados foram obtidos na dose de 400 mg/kg. Também foi observada redução na formação de edema de orelha induzida pela aplicação de óleo de cróton. Os efeitos provocados pelos extratos obtidos a partir das plantas cultivadas in vitro foram menos pronunciados que aqueles produzidos pelos extratos das plantas selvagens, embora ambos tenham sido signifi cativos. Estes resultados sugerem que o extrato etanólico de Polygala paniculata possui atividades analgésica e antiedematogênica.

Revista Brasileira de Farmacognosia, 2011

Vitex cymosa Bertero ex Spreng., Lamiaceae, is found in Central and Amazon regions of Brazil, whe... more Vitex cymosa Bertero ex Spreng., Lamiaceae, is found in Central and Amazon regions of Brazil, where it is popularly used as antirheumatic. Extracts from the leaves of V. cymosa were tested in analgesia models such as abdominal contortions induced by acetic acid and formalin to test peripheral analgesia; as well as the tail flick and hot plate models, to test spinal and supraspinal analgesia. A significant reduction was observed in the number of contortions with all extracts and in all doses. In the formalin model, a reduction in the second phase (inflammatory) was observed with all extracts, whereas only the n-butanol extract was able to act in the first, neurogenic, phase. In the tail flick model, all extracts increased latency time. Naloxone treatment reverted analgesic effect of all extracts with the exception of the dichloromethane one. All extracts developed peripheral and central analgesic activity. In the hot plate model no antinociceptive effect was observed for all tested extracts. All these results taken together suggest that V. cymosa leaf extracts were able to promote peripheral and central antinociceptive activity mediated by the opioid system.Twenty three substances were isolated and identified in the extracts and include flavonoids (C-glucosyl flavones, flavones and flavonols), triterpene acids from ursane and oleanane types, iridoids (free and glucosides), as well as simple phenols.

Revista Brasileira de Farmacognosia, 2002

Extratos de flores (ETFA) e espigas (ETEA) de Açaí (Euterpe oleraceae Mart.) foram avaliados quan... more Extratos de flores (ETFA) e espigas (ETEA) de Açaí (Euterpe oleraceae Mart.) foram avaliados quanto a sua atividade antinociceptiva. ETFA mostrou significativa atividade periférica, reduzindo em até 50% o número total de contorções abdominais. Já ETEA mostrou reduzido efeito no modelo de contorções abdominais, mas seu efeito espinhal pode ser observado com as doses maiores. Nenhum dos extratos foi capaz de alterar os índices de analgesia na placa quente.

BioMed Research International, 2013

Ampelozizyphus amazonicus is used in the treatment and prevention of malaria. The effect of an aq... more Ampelozizyphus amazonicus is used in the treatment and prevention of malaria. The effect of an aqueous extract from this plant (SART) on the immune response was investigated by measuring immunoglobulin production induced by immunization with the antigen TNP-Ficoll in Plasmodium chabaudi-infected mice. SART treatment increased antigen-specific IgM and IgG levels in TNP-Ficoll-immunized mice. The B cell response during malarial infection was also modified by SART. There was an increase in total serum IgM and IgG and a decrease in the percentage of splenic plasma cells (CD138+ cells) in P. chabaudi-infected, SART-treated animals. SART (1, 3 or 10 mg/kg, p.o.) and the reference drug dexamethasone (5 mg/kg) were also tested in carrageenan-induced leukocyte migration to the subcutaneous air pouch (SAP). All SART doses significantly reduced leukocyte migration into the SAP. The protein concentration resulting from extravasation into the peritoneum was also significantly reduced. Our data indicate that SART possesses immunomodulatory properties, inducing an in vivo modification of the B lymphocyte response and antiinflammatory properties, which are partly due to a reduction in cell migration and are most likely due to an inhibition of the production of inflammatory mediators. Preliminary HPLC-ESI-MS/MS analysis of SART shows a complex saponin profile with deprotonated molecule [M-H] − ions in the range of m/z 800-1000.

Pharmacological study of Syagrus oleracea (Martius) Beccari and Mauritia vinifera Martius fruit e... more Pharmacological study of Syagrus oleracea (Martius) Beccari and Mauritia vinifera Martius fruit extracts. The species of Palmae family are very interesting from a chemical and pharmacological point of view. However, the oil from Mauritia vinifera's fruit has being used in the treatment of burn without any previous pharmacological studies. The fruits from Syagrus oleracea haven't being studied either. This work

Toxicon, 2004

Dieffenbachia picta Schott (Araceae), known in Brazil as &amp... more Dieffenbachia picta Schott (Araceae), known in Brazil as "comigo-ninguém-pode" is an ornamental plant with toxic properties. Its juice, when chewed, causes a painful edema of the oral mucous membranes, buccal ulcerations and tongue hypertrophy. This acute inflammation sometimes becomes severe enough to produce glottis obstruction, respiratory compromise and death. Eugenol (4-alil-2-metoxiphenol), the essential oil extracted from Caryophyllus aromaticus (Myrtaceae) is widely used in odontology. In this study, our objective was to standardize, in mice, a measurable methodology for the tongue edema induced by the topical application of the D. picta stem juice; evaluate the effects of eugenol in this model and compare the results with emergency treatment used in hospitals. Our results show that in spite of a small increase in edema a few minutes after administration, emergency treatment reduced by 70% the overall edema. When compared with the combination of the above drugs, eugenol, even at the smallest dose of 5 microg/kg, regardless of the chosen administration route, or the moment the treatment began, presents better results in the reduction and inhibition of the tongue edema induced by the D. picta juice.

Rheumatology International, 2007

In this study, we evaluate the distribution of nitric oxide (NO) in the serum of juvenile idiopat... more In this study, we evaluate the distribution of nitric oxide (NO) in the serum of juvenile idiopathic arthritis (JIA) patients, correlating it with parameters of the severity of the disease. Ninety-seven patients with mean age 11.7 years and disease duration 4.8 years, showing active disease or not, grouped as oligoarticular (n = 34), polyarticular (n = 29) and systemic (n = 34) group, presenting uveitis and positive RF with erosive arthritis or active disease and erosions had signiWcantly high levels of NO than the inactive ones. NO correlated with TNF-in the oligoarticular subtype (P < 0.03), with pain in the polyarticular subtype with active disease (P < 0.04) and with ESR in the systemic subtype with active disease (P < 0.03). TNFconcentration was high in all patients with active disease, accompanying NO production. The data conWrm the production of NO in JIA patients, indicating a possible positive correlation between the production of NO and severity of the disease.

Prostaglandins & Other Lipid Mediators, 2006

There is evidence that apoptotic cells and oxidized low density lipoprotein (oxLDL) particles hav... more There is evidence that apoptotic cells and oxidized low density lipoprotein (oxLDL) particles have common ligands on their surface consisting of oxidized phospholipids which bind to scavenger receptors in macrophages leading to phagocytosis. Some effects of oxLDL binding to its receptor(s) were shown to be inhibited by Platelet Activating Factor (PAF)-receptor antagonists. Thus, we investigated the effect of PAF-receptor antagonists on the phagocytosis of apoptotic, necrotic and viable thymocytes by murine peritoneal macrophages. It was found that phagocytosis of altered cells is significantly increased compared to viable cells, a phenomenon reversed by pre-treatment of macrophages with PAF-receptor antagonists (WEB2170 and CV3988), PAF or oxLDL. Phagocytosis of altered cells induced negligible expression of cyclooxygenase-2 (COX-2) but strongly potentiated the LPS-induced expression of this enzyme. This phenomenon was restricted to altered cells and was reversed by pre-treatment of macrophages with PAF-receptor antagonists. These findings indicate that apoptotic and necrotic cells share common ligands with PAF and oxLDL and suggest the involvement of PAF-like receptors in the enhanced clearance of these cells.

Phytotherapy Research, 2003

Copaiba oil resin (COR) obtained from Copaifera multijuga Hayne has been used in popular medicine... more Copaiba oil resin (COR) obtained from Copaifera multijuga Hayne has been used in popular medicine as an antinflammatory and for the treatment of bronchitis, ulcers and cancer. The aim of this study was to evaluate the action of COR and its fractions on the inhibition of lung metastasis and tumour growth induced by B16F10 melanoma cells in mice and cytotoxicity in vitro using Trypan Blue exclusion method and MTT conversion.

Phytochemistry, 2010

Verbenaceae HSCCC Scutellarein-7-O-b-D-apiofuranoside Apigenin-7-O-b-D-apiofuranosyl-(1 ? 2)-b-D-... more Verbenaceae HSCCC Scutellarein-7-O-b-D-apiofuranoside Apigenin-7-O-b-D-apiofuranosyl-(1 ? 2)-b-D-apiofuranoside Celtidifoline 1D and 2D NMR spectroscopy Sedative activity Benzodiazepine receptor a b s t r a c t The flavone glycosides, named scutellarein-7-O-b-D-apiofuranoside and apigenin-7-O-b-D-apiofuranosyl-

Pharmacology Biochemistry and Behavior, 2013

Convolutamydine A, an oxindole that originated from a marine bryozoan, has several biological eff... more Convolutamydine A, an oxindole that originated from a marine bryozoan, has several biological effects. In this study, we aimed to investigate the antinociceptive effects of convolutamydine A and two new synthetic analogues. Convolutamydine A and the two analogues were given orally to assess their ability to induce antinociceptive effects. Formalin-induced licking response, acetic acid-induced contortions, and hot plate models were used to characterize the effects of convolutamydine A and its analogues. Convolutamydine A (4,6-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole), compound 1 (3-(2-oxopropyl)-3-hydroxy-2-oxindole), and compound 2 (5-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole) caused peripheral antinociceptive and anti-inflammatory effects in the acetic acid-induced contortions and the formalin-induced licking models. Supraspinal effects were also observed in the hot plate model and were similar to those obtained with morphine. The peripheral effects were not mediated by the cholinergic or opioid systems. The antinociceptive effects of convolutamydine A seem to be mediated by all three systems (cholinergic, opioid, and nitric oxide systems), and the mechanism of action of compounds 1 and 2 involved cholinergic and nitric oxide-mediated mechanisms. Convolutamydine A and its analogues (compounds 1 and 2) showed good antinociceptive ability after systemic administration in acute pain models. The antinociceptive action mediated by cholinergic, opioid, and nitric oxide systems could explain why convolutamydine A, compound 1, and compound 2 retained their antinociceptive effects. The doses used were similar to the doses of morphine and were much lower than that of acetylsalicylic acid, the classical analgesic and anti-inflammatory drug. In conclusion, convolutamydine A and the two analogues demonstrated antinociceptive effects comparable to morphine&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s effects.

Peptides, 2011

The present study investigated the effects of a new bradykinin B(1) receptor antagonist, R-954, o... more The present study investigated the effects of a new bradykinin B(1) receptor antagonist, R-954, on the development of Ehrlich ascitic tumor (EAT) induced by the intraperitoneal inoculation of EAT cells in mice and the formation of a solid tumor by the subcutaneous injection of the cells in rat paw. The development of the tumor was associated with an increase in mouse total cell counts in bone marrow (10.8-fold), ascitic fluid (14.6-fold), and blood (12.6-fold). R-954 (2mg/kg, s.c.) significantly reduced the ascitic fluid volume (63.7%) and the mouse weight gain (30.5%) after 10 consecutive days of treatment. The B(1) antagonist as well as the anti-neoplasic drug vincristine also significantly inhibited the increase in total cell count in bone marrow, ascitic fluid, and blood. R-954 reduced significantly the total protein extravasation (57.3%), the production of nitric oxide (56%), PGE(2) production (82%), and TNFα release (85.7%) in mice peritoneal cavity whereas vincristine reduced the release of these inflammatory mediators by 84-94%. The increase in paw edema after intraplantar injection of EAT cells was reduced by approximately 52% by either R-954 or vincristine treatment. In conclusion, this study presents for the first time the antitumoral activity of a new bradykinin B(1) receptor antagonist on ascitic and solid tumors induced by Ehrlich cell inoculation in mice and rats.

European Journal of Cell Biology

We have investigated the relationship between peritoneal murine macrophage cytoskeleton and nitri... more We have investigated the relationship between peritoneal murine macrophage cytoskeleton and nitric oxide (NO) synthase (NOS). Activation of the cells with lipopolysaccharide plus interferon-gamma (LI) induced iNOS, detected by nitrite or by labeled L-citrulline production and by a specific antibody against macrophage iNOS. Addition of cytochalasin B (a microfilament-depolymerizing agent) caused a dose-dependent inhibition in NO production by macrophages, whereas colchicine (a microtubule depolymerizing agent) inhibited it only by 20% and not dose-dependently. Addition of cytochalasin B together with LI abolished nitrite and L-citrulline accumulation as well as the amount of iNOS antigen in activated macrophage. Moreover, addition of cytochalasin B 6 or 12 h after stimulus, also decreased the nitrite and L-citrulline production by macrophages although iNOS antigen content by Western blot was the same in the presence or in the absence of cytochalasin B added 12 h after activation. Since cytochalasin B failed to inhibit iNOS activity directly, its inhibitory effects on NO production by macrophages is likely to be indirect, through microfilament network in central regions of cells, but not in filaments seen at pseudopodia or edging processes. Our findings demonstrate that disruption of microfilaments but not of microtubules prevents the iNOS induction process and inhibits its enzymatic activity in activated macrophages.

ChemMedChem, 2015

Inhibitor of nuclear factor κB kinase 2 (IKK2) is suggested to be a potential target for the deve... more Inhibitor of nuclear factor κB kinase 2 (IKK2) is suggested to be a potential target for the development of novel anti-inflammatory and anticancer drugs. In this work, we applied structure-based drug design to improve the potency of the inhibitor (E)-N&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-(4-nitrobenzylidene)-2-naphthohydrazide (LASSBio-1524, 1 a: IC50 =20 μM). The molecular model built for IKK2 together with the docking methodology employed were able to provide important and consistent information with respect to the structural and chemical inhibitor characteristics that may confer potency to IKK2 inhibitors, providing important guidelines for the development of a new N-acylhydrazone (NAH) derivative. (E)-N&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-(4-(1H-pyrrolo[2,3-b]pyridin-4-yl)benzylidene)-2-naphthohydrazide hydrochloride (LASSBio-1829 hydrochloride, 10) is a 7-azaindole NAH able to inhibit IKK2 with an IC50 value of 3.8 μM. LASSBio-1829 hydrochloride was found to be active in several pharmacological inflammation tests in vivo, showing its potential as an anti-inflammatory prototype.

Effects of a nanocomposite containing Orbignya speciosa lipophilic extract on Benign Prostatic Hy... more Effects of a nanocomposite containing Orbignya speciosa lipophilic extract on Benign Prostatic Hyperplasia.

Cocos nucifera cultivated in Brazil is known as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more Cocos nucifera cultivated in Brazil is known as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;coco-da-Bahia&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; or &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;coqueiro-da-India&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;. The tea from the husk fiber is widely used to several inflammatory disorders. Crude extract and fractions obtained from Cocos nucifera &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;common variety&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; were evaluated to test the anti-inflammatory and antinociceptive activities. Crude extract (CE, 50, 100, and 150 mg/kg), fraction 1 (F1, molecular weight lesser than 1 kDa, 1, 10, and 50mg/kg), fraction 2 (F2, molecular weight higher than 1 kDa, 1, 10, and 50mg/kg), and the references drugs morphine (5mg/kg), acetilsalicilic acid (200mg/kg), prometazine (30 mg/kg), and metisergide (5mg/kg) were evaluated on models of analgesia and inflammation. CE, F1, and F2 significantly develop peripheral and central antinociceptive activity but with less effect on supra-spinal regions of the brain. Administration of the opioid antagonist, naloxone (5mg/kg) inhibited the antinociceptive effect indicating that Cocos nucifera crude extract and fractions may be acting in opioid receptors. CE and F1 also inhibited rat paw edema induced by histamine, and serotonin. results demonstrated that Cocos nucifera and its fractions have antinociceptive and anti-inflammatory activities which confirm the popular use of this plant in several inflammatory disorders.

International Journal of Molecular Medicine, 2000

We studied the kinetics of in vivo nitrite production in the inflammatory reaction induced by M. ... more We studied the kinetics of in vivo nitrite production in the inflammatory reaction induced by M. bovis BCG into the pleural space. Pleural macrophages harvested from C57Bl/6 mice after acute BCG infection produced high levels of nitric oxide (NO). Enhanced production was obtained upon stimulation with LPS plus IFN-gamma. In sharp contrast, macrophages from DBA-2 mice produced low levels of NO, as nitrite, at the same time interval (24 h after BCG infection), being completely refractory to further stimulation. After the third day, NO production was similar in both strains. There was a close relationship between nitrite levels in the pleural exudate in vivo and those produced by harvested macrophages in vitro. In this in vivo system, the pattern of NO production by pleural macrophages one day after BCG infection was discrepant and unexpected in the response of C57Bl/6 and DBA-2 mice. However, this early response did not affect the late progressive NO production in both mice strains, that may be responsible to the late control of the mycobacteria growth.

Revista Brasileira de Farmacognosia, 2003

Araújo H.M.; Riveros-Moreno, V.; Assreuy J. Depolymerisation of macrophage filaments prevents ind... more Araújo H.M.; Riveros-Moreno, V.; Assreuy J. Depolymerisation of macrophage filaments prevents induction and inhibits activity of nitric oxide synthase.

Revista Brasileira de Farmacognosia, 2005

Revista Brasileira de Farmacognosia Brazilian Journal of Pharmacognosy 15(4): 310-315, Out./Dez. ... more Revista Brasileira de Farmacognosia Brazilian Journal of Pharmacognosy 15(4): 310-315, Out./Dez. 2005 RESUMO: Polygala paniculata L. (Polygalaceae) é uma erva que ocorre em todas as regiões do Brasil. No presente trabalho, foram avaliadas as atividades analgésica, através do teste da placa quente, da retirada de cauda e da formalina, e antiedematogênica, através do teste do edema de orelha induzido por óleo de cróton, dos extratos etanólicos obtidos das partes aéreas de Polygala paniculata selvagem e cultivadas por micropropagação. A aplicação oral do extrato etanólico de Polygala paniculata apresentou atividade analgésica, em ratos, tanto em testes de dor induzida por agentes térmicos (testes da placa quente e de retirada da cauda) quanto por agentes químicos (teste da formalina), de modo que os melhores resultados foram obtidos na dose de 400 mg/kg. Também foi observada redução na formação de edema de orelha induzida pela aplicação de óleo de cróton. Os efeitos provocados pelos extratos obtidos a partir das plantas cultivadas in vitro foram menos pronunciados que aqueles produzidos pelos extratos das plantas selvagens, embora ambos tenham sido signifi cativos. Estes resultados sugerem que o extrato etanólico de Polygala paniculata possui atividades analgésica e antiedematogênica.

Revista Brasileira de Farmacognosia, 2011

Vitex cymosa Bertero ex Spreng., Lamiaceae, is found in Central and Amazon regions of Brazil, whe... more Vitex cymosa Bertero ex Spreng., Lamiaceae, is found in Central and Amazon regions of Brazil, where it is popularly used as antirheumatic. Extracts from the leaves of V. cymosa were tested in analgesia models such as abdominal contortions induced by acetic acid and formalin to test peripheral analgesia; as well as the tail flick and hot plate models, to test spinal and supraspinal analgesia. A significant reduction was observed in the number of contortions with all extracts and in all doses. In the formalin model, a reduction in the second phase (inflammatory) was observed with all extracts, whereas only the n-butanol extract was able to act in the first, neurogenic, phase. In the tail flick model, all extracts increased latency time. Naloxone treatment reverted analgesic effect of all extracts with the exception of the dichloromethane one. All extracts developed peripheral and central analgesic activity. In the hot plate model no antinociceptive effect was observed for all tested extracts. All these results taken together suggest that V. cymosa leaf extracts were able to promote peripheral and central antinociceptive activity mediated by the opioid system.Twenty three substances were isolated and identified in the extracts and include flavonoids (C-glucosyl flavones, flavones and flavonols), triterpene acids from ursane and oleanane types, iridoids (free and glucosides), as well as simple phenols.

Revista Brasileira de Farmacognosia, 2002

Extratos de flores (ETFA) e espigas (ETEA) de Açaí (Euterpe oleraceae Mart.) foram avaliados quan... more Extratos de flores (ETFA) e espigas (ETEA) de Açaí (Euterpe oleraceae Mart.) foram avaliados quanto a sua atividade antinociceptiva. ETFA mostrou significativa atividade periférica, reduzindo em até 50% o número total de contorções abdominais. Já ETEA mostrou reduzido efeito no modelo de contorções abdominais, mas seu efeito espinhal pode ser observado com as doses maiores. Nenhum dos extratos foi capaz de alterar os índices de analgesia na placa quente.

BioMed Research International, 2013

Ampelozizyphus amazonicus is used in the treatment and prevention of malaria. The effect of an aq... more Ampelozizyphus amazonicus is used in the treatment and prevention of malaria. The effect of an aqueous extract from this plant (SART) on the immune response was investigated by measuring immunoglobulin production induced by immunization with the antigen TNP-Ficoll in Plasmodium chabaudi-infected mice. SART treatment increased antigen-specific IgM and IgG levels in TNP-Ficoll-immunized mice. The B cell response during malarial infection was also modified by SART. There was an increase in total serum IgM and IgG and a decrease in the percentage of splenic plasma cells (CD138+ cells) in P. chabaudi-infected, SART-treated animals. SART (1, 3 or 10 mg/kg, p.o.) and the reference drug dexamethasone (5 mg/kg) were also tested in carrageenan-induced leukocyte migration to the subcutaneous air pouch (SAP). All SART doses significantly reduced leukocyte migration into the SAP. The protein concentration resulting from extravasation into the peritoneum was also significantly reduced. Our data indicate that SART possesses immunomodulatory properties, inducing an in vivo modification of the B lymphocyte response and antiinflammatory properties, which are partly due to a reduction in cell migration and are most likely due to an inhibition of the production of inflammatory mediators. Preliminary HPLC-ESI-MS/MS analysis of SART shows a complex saponin profile with deprotonated molecule [M-H] − ions in the range of m/z 800-1000.

Pharmacological study of Syagrus oleracea (Martius) Beccari and Mauritia vinifera Martius fruit e... more Pharmacological study of Syagrus oleracea (Martius) Beccari and Mauritia vinifera Martius fruit extracts. The species of Palmae family are very interesting from a chemical and pharmacological point of view. However, the oil from Mauritia vinifera's fruit has being used in the treatment of burn without any previous pharmacological studies. The fruits from Syagrus oleracea haven't being studied either. This work

Toxicon, 2004

Dieffenbachia picta Schott (Araceae), known in Brazil as &amp;amp;amp;amp;amp;amp;amp;amp;amp... more Dieffenbachia picta Schott (Araceae), known in Brazil as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;comigo-ninguém-pode&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; is an ornamental plant with toxic properties. Its juice, when chewed, causes a painful edema of the oral mucous membranes, buccal ulcerations and tongue hypertrophy. This acute inflammation sometimes becomes severe enough to produce glottis obstruction, respiratory compromise and death. Eugenol (4-alil-2-metoxiphenol), the essential oil extracted from Caryophyllus aromaticus (Myrtaceae) is widely used in odontology. In this study, our objective was to standardize, in mice, a measurable methodology for the tongue edema induced by the topical application of the D. picta stem juice; evaluate the effects of eugenol in this model and compare the results with emergency treatment used in hospitals. Our results show that in spite of a small increase in edema a few minutes after administration, emergency treatment reduced by 70% the overall edema. When compared with the combination of the above drugs, eugenol, even at the smallest dose of 5 microg/kg, regardless of the chosen administration route, or the moment the treatment began, presents better results in the reduction and inhibition of the tongue edema induced by the D. picta juice.

Rheumatology International, 2007

In this study, we evaluate the distribution of nitric oxide (NO) in the serum of juvenile idiopat... more In this study, we evaluate the distribution of nitric oxide (NO) in the serum of juvenile idiopathic arthritis (JIA) patients, correlating it with parameters of the severity of the disease. Ninety-seven patients with mean age 11.7 years and disease duration 4.8 years, showing active disease or not, grouped as oligoarticular (n = 34), polyarticular (n = 29) and systemic (n = 34) group, presenting uveitis and positive RF with erosive arthritis or active disease and erosions had signiWcantly high levels of NO than the inactive ones. NO correlated with TNF-in the oligoarticular subtype (P < 0.03), with pain in the polyarticular subtype with active disease (P < 0.04) and with ESR in the systemic subtype with active disease (P < 0.03). TNFconcentration was high in all patients with active disease, accompanying NO production. The data conWrm the production of NO in JIA patients, indicating a possible positive correlation between the production of NO and severity of the disease.

Prostaglandins & Other Lipid Mediators, 2006

There is evidence that apoptotic cells and oxidized low density lipoprotein (oxLDL) particles hav... more There is evidence that apoptotic cells and oxidized low density lipoprotein (oxLDL) particles have common ligands on their surface consisting of oxidized phospholipids which bind to scavenger receptors in macrophages leading to phagocytosis. Some effects of oxLDL binding to its receptor(s) were shown to be inhibited by Platelet Activating Factor (PAF)-receptor antagonists. Thus, we investigated the effect of PAF-receptor antagonists on the phagocytosis of apoptotic, necrotic and viable thymocytes by murine peritoneal macrophages. It was found that phagocytosis of altered cells is significantly increased compared to viable cells, a phenomenon reversed by pre-treatment of macrophages with PAF-receptor antagonists (WEB2170 and CV3988), PAF or oxLDL. Phagocytosis of altered cells induced negligible expression of cyclooxygenase-2 (COX-2) but strongly potentiated the LPS-induced expression of this enzyme. This phenomenon was restricted to altered cells and was reversed by pre-treatment of macrophages with PAF-receptor antagonists. These findings indicate that apoptotic and necrotic cells share common ligands with PAF and oxLDL and suggest the involvement of PAF-like receptors in the enhanced clearance of these cells.

Phytotherapy Research, 2003

Copaiba oil resin (COR) obtained from Copaifera multijuga Hayne has been used in popular medicine... more Copaiba oil resin (COR) obtained from Copaifera multijuga Hayne has been used in popular medicine as an antinflammatory and for the treatment of bronchitis, ulcers and cancer. The aim of this study was to evaluate the action of COR and its fractions on the inhibition of lung metastasis and tumour growth induced by B16F10 melanoma cells in mice and cytotoxicity in vitro using Trypan Blue exclusion method and MTT conversion.

Phytochemistry, 2010

Verbenaceae HSCCC Scutellarein-7-O-b-D-apiofuranoside Apigenin-7-O-b-D-apiofuranosyl-(1 ? 2)-b-D-... more Verbenaceae HSCCC Scutellarein-7-O-b-D-apiofuranoside Apigenin-7-O-b-D-apiofuranosyl-(1 ? 2)-b-D-apiofuranoside Celtidifoline 1D and 2D NMR spectroscopy Sedative activity Benzodiazepine receptor a b s t r a c t The flavone glycosides, named scutellarein-7-O-b-D-apiofuranoside and apigenin-7-O-b-D-apiofuranosyl-

Pharmacology Biochemistry and Behavior, 2013

Convolutamydine A, an oxindole that originated from a marine bryozoan, has several biological eff... more Convolutamydine A, an oxindole that originated from a marine bryozoan, has several biological effects. In this study, we aimed to investigate the antinociceptive effects of convolutamydine A and two new synthetic analogues. Convolutamydine A and the two analogues were given orally to assess their ability to induce antinociceptive effects. Formalin-induced licking response, acetic acid-induced contortions, and hot plate models were used to characterize the effects of convolutamydine A and its analogues. Convolutamydine A (4,6-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole), compound 1 (3-(2-oxopropyl)-3-hydroxy-2-oxindole), and compound 2 (5-bromo-3-(2-oxopropyl)-3-hydroxy-2-oxindole) caused peripheral antinociceptive and anti-inflammatory effects in the acetic acid-induced contortions and the formalin-induced licking models. Supraspinal effects were also observed in the hot plate model and were similar to those obtained with morphine. The peripheral effects were not mediated by the cholinergic or opioid systems. The antinociceptive effects of convolutamydine A seem to be mediated by all three systems (cholinergic, opioid, and nitric oxide systems), and the mechanism of action of compounds 1 and 2 involved cholinergic and nitric oxide-mediated mechanisms. Convolutamydine A and its analogues (compounds 1 and 2) showed good antinociceptive ability after systemic administration in acute pain models. The antinociceptive action mediated by cholinergic, opioid, and nitric oxide systems could explain why convolutamydine A, compound 1, and compound 2 retained their antinociceptive effects. The doses used were similar to the doses of morphine and were much lower than that of acetylsalicylic acid, the classical analgesic and anti-inflammatory drug. In conclusion, convolutamydine A and the two analogues demonstrated antinociceptive effects comparable to morphine&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s effects.

Peptides, 2011

The present study investigated the effects of a new bradykinin B(1) receptor antagonist, R-954, o... more The present study investigated the effects of a new bradykinin B(1) receptor antagonist, R-954, on the development of Ehrlich ascitic tumor (EAT) induced by the intraperitoneal inoculation of EAT cells in mice and the formation of a solid tumor by the subcutaneous injection of the cells in rat paw. The development of the tumor was associated with an increase in mouse total cell counts in bone marrow (10.8-fold), ascitic fluid (14.6-fold), and blood (12.6-fold). R-954 (2mg/kg, s.c.) significantly reduced the ascitic fluid volume (63.7%) and the mouse weight gain (30.5%) after 10 consecutive days of treatment. The B(1) antagonist as well as the anti-neoplasic drug vincristine also significantly inhibited the increase in total cell count in bone marrow, ascitic fluid, and blood. R-954 reduced significantly the total protein extravasation (57.3%), the production of nitric oxide (56%), PGE(2) production (82%), and TNFα release (85.7%) in mice peritoneal cavity whereas vincristine reduced the release of these inflammatory mediators by 84-94%. The increase in paw edema after intraplantar injection of EAT cells was reduced by approximately 52% by either R-954 or vincristine treatment. In conclusion, this study presents for the first time the antitumoral activity of a new bradykinin B(1) receptor antagonist on ascitic and solid tumors induced by Ehrlich cell inoculation in mice and rats.