DEFAR - Departamento de Farmácia
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Item Anti-inflammatory sesquiterpene lactones from Lychnophora trichocarpha Spreng. (Brazilian Arnica).(2013) Ferrari, Fernanda Cristina; Ferreira, Leidiane Cristina; Souza, Maíra Ribeiro de; Guimarães, Andrea Grabe; Paula, Carmem Aparecida de; Rezende, Simone Aparecida; Guimarães, Dênia Antunes SaúdeThe aerial parts of Lychnophora trichocarpha Spreng. (Asteraceae) are used macerated in water or ethanol to treat inflammation, pain, rheumatism, contusions, bruises and insect bites in Brazilian traditional medicine. In this study, anti-inflammatory activity of ethanol extract from aerial parts of L. trichocarpha and its ethyl acetate fraction was investigated. Sesquiterpene lactones, lychnopholide (Lyc) and eremantholide C (EreC), isolated of ethyl acetate fraction, were also assayed for in vitro and in vivo anti-inflammatory activity. Topical treatment with ointments containing ethanol extract, its ethyl acetate fraction and sesquiterpene lactones significantly reduced carrageenan-induced mice paw oedema. In vitro assays demonstrated that Lyc inhibited interferon - g/lipopolysaccharide -stimulated nitric oxide (NO) production in J774A.1 macrophages and increased production of IL-10 anti-inflammatory cytokine. The reduction of tumor necrosis factor-a (TNF-a) production by EreC was accompanied by an increased production of IL-10 in a concentration-dependent manner in J774A.1 macrophages. The anti-inflammatory effect of Lyc seems to involve the inhibition of production of NO and increased production of IL-10. The mechanism of the effect of EreC on the reduction of carrageenan-induced paw oedema may be attributed to inhibition of production of TNF-a and stimulation of IL-10 production. The results corroborate the use of ethanol extract from Lychnophora trichocarpha in folk medicine for anti-inflammatory action and indicate that the topical route is suitable for use.Item Protein-energy malnutrition decreases immune response to Leishmania chagasi vaccine in BALB/c mice.(2009) Malafaia, Guilherme; Serafim, Tiago Donatelli; Silva, Marcelo Eustáquio; Pedrosa, Maria Lúcia; Rezende, Simone AparecidaProtein-energy malnutrition and visceral leishmaniasis are important problems of public health affecting millions of people worldwide. Vaccine efficacy depends on the ability of individuals to mount an appropriate immune response and may be inadequate in malnourished persons. In this study, we used a mouse model to verify the effect of combined protein, iron and zinc deficiency in the response to Leishmania chagasi antigen vaccine. BALB/c mice were fed with a low-protein (3% casein), iron- and zinc-deficient diet or control diet (14% casein and sufficient in zinc and iron). After malnutrition establishment, mice were vaccinated subcutaneously with L. chagasi Ag plus saponin. After vaccination, mice were nutritionally repleted and then all mice were challenged with L. chagasi promastigotes. Four weeks later, liver and spleen parasite load was evaluated. Our data show that vaccine caused a significant reduction in parasite load in spleen and liver from mice fed with control diet. However, splenic parasitism was increased in mice fed with deficient diet and this diet caused a reduction in splenocyte IFN-γ production in response to the vaccine in repleted mice. These data suggest that malnutrition may alter immune response to L. chagasi vaccine in BALB/c model of infection, even after nutritional repletion.Item Leishmania chagasi : effect of the iron deficiency on the infection in BALB/c mice.(2011) Malafaia, Guilherme; Marcon, Letícia de Nadai; Pereira, Liliane de Fátima; Pedrosa, Maria Lúcia; Rezende, Simone AparecidaIron deficiency and visceral leishmaniasis are serious problems of public health. The aim of this study was to evaluate the effect of iron deficiency, induced by the iron chelator desferrioxamine, on the course of the infection by Leishmania chagasi in BALB/c mice. Our data show that the iron chelator caused significant reduction in hemoglobin concentration of treated mice and reduction in parasite load in spleen and liver. Significant differences were not observed in the production of IFN-gamma and IL-4 among the experimental groups. In conclusion, the data reported in this paper suggest that iron deficiency may favor the host. If there is not enough iron available to the parasite, its multiplication may be reduced and infection attenuated.Item Intramuscular immunization with p36(LACK) DNA vaccine induces IFN-gama production but does not protect BALB/c mice against Leishmania chagasi intravenous challenge.(2005) Silva, Eduardo de Almeida Marques da; Coelho, Eduardo Antônio Ferraz; Gomes, Daniel Cláudio de Oliveira; Vilela, Márcia de Carvalho; Masioli, Cássio Zumerle; Tavares, Carlos Alberto Pereira; Fernandes, Ana Paula Salles Moura; Afonso, Luís Carlos Crocco; Rezende, Simone AparecidaAcute visceral leishmaniasis is a progressive disease caused by Leishmania chagasi in South America. The acquisition of immunity following infection suggests that vaccination is a feasible approach to protect against this disease. Since Leishmania homologue of receptors for activated C kinase (LACK) antigen is of particular interest as a vaccine candidate because of the prominent role it plays in the pathogenesis of experimental Leishmania major infection, we evaluated the potential of a p36(LACK) DNA vaccine in protecting BALB/c mice challenged with L. chagasi. In this study, mice received intramuscular (i.m.) or subcutaneous (s.c.) doses of LACK DNA vaccine. We evaluated the production of vaccine-induced cytokines and whether this immunization was able to reduce parasite load in liver and spleen. We detected a significant production of interferon gamma by splenocytes from i.m. vaccinated mice in response to L. chagasi antigen and to rLACK protein. However, we did not observe a reduction in parasite load neither in liver nor in the spleen of vaccinated animals. The lack of protection observed may be explained by a significant production of IL-10 induced by the vaccine.Item IL-10 plays a role in modulation of human granulomatous hypersensitivity against Schistosoma mansoni eggs induced by immune complexes.(1997) Rezende, Simone Aparecida; Teixeira, David Nascimento Silva; Drummond, Sandra Costa; Goes, Alfredo Miranda deIt has been demonstrated that the chronic intestinal form of schistosomiasis is associated with the establishment and maintenance of a variety of immunoregulatory mechanisms that lead to a diminished granulomatous reaction to parasite eggs. Using an in vitro model of granuloma reaction we showed that immune complexes (IC) isolated from the sera of chronic intestinal schistosomiasis patients were able to reduce the granulomatous hypersensitivity (developed by peripheral blood mononuclear cells (PBMC) from schistosomiasis patients) to soluble egg antigen (SEA)-conjugated polyacrylamide beads (PB–SEA). This inhibitory activity, mediated by IC, was also observed in the proliferative response of PBMC stimulated with SEA and soluble worm antigen preparation (SWAP). Furthermore, we observed a decrease in TNF-α and an increase in IL-10 production by PBMC treated with IC in an in vitro granuloma reaction. This phenomenon was also seen in a cell proliferation assay when PBMC were treated with IC and stimulated with S. mansoni antigens. These results demonstrate that circulating IC may down-regulate PBMC reactivity to S. mansoni antigens by changing the cytokine pattern produced by these cells.Item Granulomatous hypersensitivity to Schistosoma mansoni egg antigens in human schistosomiasis. IV. A role for prostaglandin-induced inhibition of in vitro granuloma formation.(1994) Goes, Alfredo Miranda de; Rezende, Simone Aparecida; Gazzinelli, Giovanni; Doughty, Barbara L.The prostaglandins (PG) are known to regulate immune cell function (s) and participate in the progression of both acute and chronic inflammatory reactions. Using an in vitro model of Schistosoma mansoni egg-induced hypersensitivity granulomas, we have delineated the role of immune complexes (IC) in the induction andrelease of PG and their inhibitory effects on granuloma development. The hypersensitivity- type granuloma reaction to soluble egg antigen (SEA) was examined using a model of in vitro granuloma ,formation. Our results show that granuloma formation was dramatically suppressed by the addition to the granuloma cultures of IC, PGE,, PGE2, while PGF, alpha had no significant effect. The inhibition of the PG function was achieved by the introduction of anti-PG antibodies that blocked suppression of granuloma,formation. It appears in this model system that IC may inhibit the activity of granuloma formation by stimulating the monocyte-macrophage lineage to release inhibitory mediators. Our results suggest that the prostaglandins E series may be important in the generation and maintenance of suppression of the granulomatous inflammatory response to S. mansoni egg antigens .Item Association of water extract of green propolis and liposomal meglumine antimoniate in the treatment of experimental visceral leishmaniasis.(2014) Ferreira, Flávia Monteiro; Castro, Renata Alves de Oliveira e; Batista, Maurício Azevedo; Rossi, Fernanda Mendes de Oliveira; Lemos, Denise da Silveira; Frezard, Frederic Jean Georges; Moura, Sandra Aparecida Lima de; Rezende, Simone AparecidaThis work investigated the use of water extract of green propolis (WEP) and its association with free or liposomal meglumine antimoniate (MA) for the treatment of murine visceral leishmaniasis. Mice infected with Leishmania infantum were treated with oral doses of WEP associated or not with a single dose of liposomal MA by intraperitoneal route. Parasite burden was assessed in the liver and spleen by limiting dilution assay, and alterations in the spleen cellular phenotype were evaluated by flow cytometry. Tissue damage was assessed by determination of biochemical markers of the liver, heart, and kidney function and histopathological analysis of the liver and spleen. Our data showed that treatmentwith WEP was able to reduce parasite load in the liver but not in the spleen. On the other hand, liposomal MA reduced parasite load in both organs. Unexpectedly, there was no synergism with the combination of WEP and liposomal MA in reducing the parasite load. The histopathological analysis showed that administration of WEP, liposomal MA, or their association was able to protect the liver and spleen fromlesions caused by infection. No alteration in the profile of spleen cells by flow cytometry or in the liver, heart, and kidney functions by biochemical markers due to any of the treatments was observed. These results demonstrate that althoughWEP was able to significantly reduce the liver parasite load, its association with liposomalMA did not lead to significant improvement in reducing parasite load. On the other hand, treatment with WEP and/or liposomal MA protected the liver and spleen from lesions caused by the infection.Item Anti-inflammatory and antinociceptive activities of Campomanesia adamantium.(2013) Ferreira, Lidiane Cristina; Guimarães, Andrea Grabe; Paula, Carmem Aparecida de; Michel, Marcela Carolina de Paula; Guimarães, Raquel Gomes; Rezende, Simone Aparecida; Souza Filho, José Dias de; Guimarães, Dênia Antunes SaúdeEthnopharmacological relevance: Campomanesia species are used in folk medicine as anti-inflammatory, anti-rheumatic, anti-diarrheal and hypocholesterolemic. Aim of the study: The present study investigated the in vivo anti-inflammatory and antinociceptive properties of ethyl acetate (AE) and aqueous (Aq) extracts from leaves of Campomanesia adamantium and in vitro anti-inflammatory activity of AE and its isolated flavonols, myricitrin and myricetin. Materials and methods: The antinociceptive activity of AE and Aq was evaluated using acetic acid- induced writhing and formalin methods. The in vivo anti-inflammatory effect of AE and Aq was evaluated using carrageenan-induced paw oedema in mice. AE, myricitrin and myricetin were evaluated for their abilities to modulate the production of NO, TNF-a and IL-10 in LPS/IFN-g stimulated J774.A1 macrophages. Results: It was found that orally administrated AE and Aq (125 and 250 mg/kg) inhibited carrageenan- induced paw oedema in mice. AE (125 and 250 mg/kg) and Aq (125 mg/kg) reduced the time to licking at the second phase of the formalin method in vivo in mice. AE (250 mg/kg) and Aq (125 mg/kg) also reduced the number of writhes. AE, myricitrin and myricetin inhibited NO (320 mg/mL and 6.25–100 mM, respectively) and TNF-a production by macrophages (320 mg/mL for AE, 100 mM for myricitrin and 25–100 mM for myricetin). AE (160 and 320 mg/mL), myricitrin (50 and 100 mM) and myricetin (25–100 mM) increased IL-10 production by macrophages. Conclusions: The ethyl acetate and aqueous extracts from Campomanesia adamantium showed anti- nociceptive and anti-inflammatory effects supporting the use of the plant in folk medicine. The results suggest that anti-oedematogenic effect promoted by aqueous extract involves several anti- inflammatory mechanisms of action. The antinociceptive effect shown by aqueous extract can be due to the modulation of release of inflammatory mediators involved in nociception. The anti-inflammatory effects of AE and of its isolated flavonols may be attributed to inhibition of pro-inflammatory cytokines production, TNF-a and NO and to the increased of IL-10 production.Item Anti-inflammatory activity of Lychnophora passerina, Asteraceae (Brazilian Arnica).(2011) Oliveira, Patricia Capelari de; Paula, Carmem Aparecida de; Rezende, Simone Aparecida; Campos, Fernanda Torres; Guimarães, Andrea Grabe; Lombardi, Júlio Antônio; Guimarães, Dênia Antunes SaúdeEthnopharmacological relevance: Lychnophorapasserina (Asteraceae), popularly known as “arnica,” is used to treat inflammation, pain, rheumatism, contusions, bruises and insect bites in Brazilian traditional medicine. Materials and methods: The anti-inflammatoryactivity of crude ethanolic extract of aerial parts of L. passerina and its ethyl acetate and methanolic fractions had their abilities to modulate the production of NO, TNF-α and IL-10 inflammatory mediators in LPS/IFN-γ-stimulated J774.A1 macrophages evaluated. Moreover, the crude ethanolic extract and derived fractions were also in vivo assayed by carrageenan-induced paw oedema in mice. Results: In vitro assays showed remarkable anti-inflammatoryactivity of L. passerina crude ethanolic extract (EE) and its ethyl acetate (A) and methanolic (M) fractions, through the inhibition of production of NO and TNF-α inflammatory mediators and induction of production of IL-10 anti-inflammatory cytokine. In vivo assays showed anti-inflammatoryactivity for EE 10% ointment, similar to the standard drug diclofenac gel. The A and M fraction ointments 20% presented anti-inflammatoryactivity. Conclusion: The results obtained showed that possible anti-inflammatory effects of EE and its A and M fractions may be attributed to inhibition pro-inflammatory cytokines production, TNF-α and NO and to increased IL-10 production. EE, A and M ointments showed topical in vivoanti-inflammatoryactivity. The in vivoanti-inflammatoryactivity of EE of L. passerina may be related to synergistic effects of different substances in the crude extract. Therefore, traditional use of aerial parts of L. passerina in the inflammatory conditions could be beneficial to treat topical inflammatory conditions, as evidenced by the present study.