Navegando por Autor "Sachs, Daniela"
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Item Coffea arabica extracts and their chemical constituents in a murine model of gouty arthritis : how they modulate pain and inflammation.(2022) Matosinhos, Rafaela Cunha; Bezerra, Juliana Pantaleão; Barros, Camila Helena; Bernardes, Ana Catharina Fernandes Pereira Ferreira; Araújo, Marcela Carolina de Paula Michel; Coelho, Grazielle Brandão; Soares, Rodrigo Dian de Oliveira Aguiar; Sachs, Daniela; Guimarães, Dênia Antunes SaúdeEthnopharmacological relevance: Coffea arabica is commonly known for its cardiotonic and neurotonic activities, but in some places’ folk medicine, like in Arabia and Africa, C. arabica is used to treat headache, migraine, the flu, anemia, oedema, asthenia, asthma, inflammation and wounds. Aims of the study: The aims were to evaluate if the aqueous extracts of Coffea arabica, prepared from beans with different degrees of roasting, and their main chemical constituents could exert an in vivo anti-gouty effect. Materials and methods: Coffea extracts were obtained from the beans of not roasted, light, medium and dark roasted coffee and from decaffeinated and traditional coffees and were prepared with water at 25◦C and at 98◦C. C57BL/6 mice were induced to gout by an injection of monosodium urate crystals and treated with coffee extracts at doses of 25, 75 and 225 mg/kg and their chemical constituents at a dose of 10 mg/kg. The antinociceptive and anti-inflammatory effects were evaluated. Results: Treatments with Coffea extracts prepared with water at 98◦C were more effective to exert antinociceptive and anti-inflammatory activities than the ones prepared with water at 25◦C. Caffeic and chlorogenic acids reduced hypernociception in animals when compared with negative control group (7.79 and 5.69 vs 18.53; P < 0.05 and P < 0.001, respectively), inhibited neutrophil migration (1.59 × 104 and 0.38 × 104 vs 9.47 × 104; P < 0.0001 both) and decreased pro-inflammatory cytokines concentration (IL-1β, IL-6 and TNF-α). Conclusions: We have demonstrated that our treatments attenuated gout, and this effect could be attributed to a reducement in hypernociception, neutrophil migration and cytokines concentration. These results suggest coffee as a potential candidate for studies in acute gout therapy.Item Licnofolida livre e em formulações nanoméricas : toxicidade, atividade in vitro e in vivo contra Trypanosoma cruzi e proposta de mecanismo de ação.(2022) Milagre, Matheus Marques; Lana, Marta de; Guimarães, Dênia Antunes Saúde; Lana, Marta de; Sachs, Daniela; Ferreira, Lucas Antônio Miranda; Silva, André Talvani Pedrosa da; Veloso, Vanja MariaA doença de Chagas permanece epidemiologicamente relevante e é a sexta doença mais negligenciada do mundo, causando elevada morbidade e mortalidade em plena idade produtiva. O mais grave é a falta de terapia profilática e curativa adequada para esta enfermidade, sendo os únicos medicamentos atualmente utilizados o benznidazol (BZ) e nifurtimox (NIF). Estes fármacos causam graves efeitos colaterais e apresentam limitada eficácia terapêutica na fase crônica da doença, justificando a busca por novas opções terapêuticas. Este trabalho visou avançar nos estudos da lactona sesquiterpênica licnofolida (LIC-livre) e em nanocápsulas (LIC- NC) avaliando a citotoxicidade in vitro células cardíacas H9c2 e hepáticas HepG2 pelos métodos de vermelho neutro; sua interferência no ciclo celular e na produção de espécies reativas de oxigênio (EROs); genotoxicidade por ensaio cometa; fenômenos de apoptose e necrose; seletividade para T. cruzi em comparação à células H9c2; análise qualitativa da incorporação das NC fluorescente pelas células e parasitos na tentativa de explicar o mecanismo de ação de LIC-NC na infecção por T. cruzi; avaliar a toxicidade aguda in vivo da LIC-livre e LIC-NC; bem como sua eficácia terapêutica contra a cepa Colombiana de T. cruzi, protótipo de resistência ao tratamento por BZ e NIF. O tratamento com BZ foi utilizado como grupo controle de referência. No teste de vermelho neutro LIC-livre e LIC-NC apresentaram IC50 de 1,69μM e 3,28μM em células H9c2 e IC50 de 3,11μM e 3,69μM em células HepG2. Não foram observadas diferenças significativas entre as células na análise da evolução do ciclo celular, tampouco na comparação dos tratamentos com LIC-livre e LIC-NC. Verificou-se aumento nas fases sub-G1 e diminuição nas fases G2-M com ambas as formulações. Não foram observadas diferenças significativas nas análises de apoptose e necrose entre LIC-livre e LIC-NC. Em células H9c2, LIC-livre, LIC-NC, NC-BR e BZ aumentaram a produção de EROs. LIC-livre e BZ induziram aumento na intensidade da cauda nas células H9c2, diferentemente das células HepG2. Os testes em amastigota e epimastigota mostraram que LIC-livre possui maior ação tripanocida in vitro quando comparada à LIC-NC. LIC-NC foi incorporada tanto pelas células H9c2 não infectadas, quanto infectadas, e por tripomastigotas, mostrando boa entrega da formulação nos sítios de interesse. No teste de toxicidade aguda não foram observadas alterações significativas quanto aos parâmetros avaliados. LIC-NC curou 80% dos animais infectados com a cepa Colombiana, 100% resistente aos fármacos de referência, com negativação de todos os parâmetros avaliados (hemocultura, qPCR sanguínea e em tecido cardíaco após imunossupressão e ELISA). A licnofolida se mostrou eficaz em sua ação anti-T. cruzi in vitro e in vivo, na sua forma livre e nanoencapsulada, com diminuição da citotoxicidade quando encapsulada, e melhora significativa da sua ação tripanocida in vivo. LIC ainda se mostrou menos citotóxica em todos os parâmetros avaliados em relação ao grupo controle BZ. Ambas as formulações se mostraram seguras quanto ao uso em camundongos, principalmente a LIC-NC que foi também mais eficaz na cura da infecção por T. cruzi. Em conjunto, os resultados incentivam estudos complementares da LIC-NC como uma nova opção terapêutica a ser explorada e utilizada no tratamento da doença de Chagas.Item Lychnophora pinaster’s effects on inflammation and pain in acute gout.(2021) Barros, Camila Helena; Matosinhos, Rafaela Cunha; Bernardes, Ana Catharina Fernandes Pereira Ferreira; Araújo, Marcela Carolina de Paula Michel; Bezerra, Juliana Pantaleão; Sachs, Daniela; Soares, Rodrigo Dian de Oliveira Aguiar; Guimarães, Dênia Antunes SaúdeEthnopharmacological relevance: Ethanolic extract of aerial parts from Lychnophora pinaster Mart. are used in traditional Brazilian medicine for treating pain, rheumatism and inflammation. Aim of the study: Drugs for the treatment of gout present severe adverse effects, justifying the need to search for new therapeutic options. The aim of the present study was to evaluate the effects of the ethanolic extract of L. pinaster and its main constituents in arthritis induced in mice by the injection of monosodium urate (MSU) crystals. Materials and methods: Antinociceptive effect was investigated using an electronic pressure-meter nociception paw test in C57BL/6 mice. Anti-gouty arthritis was investigated in mice induced with gout by the injection of MSU crystals into their femur-tibial tissue. Ethanolic extract of the aerial parts of Lychnophora pinaster and its main chemical constituents were evaluated as treatment. Results: The ethanolic extract and their main chemical constituents inhibited neutrophil migration, reduced IL-1β and TNF-α concentrations in the inflamed tissue and showed antinociceptive activity. Conclusions: Gouty arthritis effects of the ethanolic extract can be attached to a synergistic effect of terpenes, flavonoids and phenolic acids present in the extract. Results obtained support the use of this extract and its main chemical constituents in the treatment of gout, inflammation, and pain.Item Sesquiterpene lactones from Lychnophora species : antinociceptive, anti-inflammatory, and antioxidant pathways to treat acute gout.(2021) Bernardes, Ana Catharina Fernandes Pereira Ferreira; Matosinhos, Rafaela Cunha; Araújo, Marcela Carolina de Paula Michel; Barros, Camila Helena; Soares, Rodrigo Dian de Oliveira Aguiar; Costa, Daniela Caldeira; Sachs, Daniela; Guimarães, Dênia Antunes SaúdeEthnopharmacological relevance: Lychnophora trichocarpha and Lychnophora passerina are species used in folk medicine to treat inflammation, pain, and rheumatism. Previous studies have demonstrated the antiinflammatory effect of ethanol extracts of these species and identified that sesquiterpene lactones contribute to this activity. Aim of the study: Gout is an acute inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints. Inflammation in joints induces oxidative stress in defense cells, releasing pro-inflammatory mediators. This study has three objectives: (1) to demonstrate the effects of sesquiterpene lactones lychnopholide and eremantholide C isolated from L. trichocarpha and goyazensolide isolated from L. passerina on arthritis induced by MSU crystals in C57BL6 mice; (2) to determine whether or not these compounds can inhibit the migration of neutrophils and the release of TNF-α and IL-1β cytokines in the inflammation region; and (3) to evaluate the effects of sesquiterpene lactones on the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in the cartilage of C57BL/6 mice with gouty arthritis. Materials and methods: The anti-inflammatory, antinociceptive, and antioxidant activities of sesquiterpene lactones in C57BL/6 mice with MSU crystal-induced arthritis were evaluated. In our experimental model, the mice were injected with MSU crystals in the tibiofemoral joint to induce arthritis and then treated with indomethacin, vitamin C, and sesquiterpene lactones. Nociception was evaluated before and after inflammation induction and treatments, neutrophil migration, IL-1β and TNF-α concentrations, and SOD and CAT activities. Results: Sesquiterpene lactones exerted an anti-inflammatory effect by inhibiting neutrophil migration and TNF-α production. These compounds also demonstrated antinociceptive and antioxidant activities. Conclusion: Lychnopholide, eremantholide C, and goyazensolide improved the inflammation induced by MSU crystals by inhibiting the migration of neutrophils to the inflamed area and by blocking the release of the proinflammatory cytokine TNF-α. In addition, sesquiterpene lactones reduced oxidative stress by activating SOD and CAT. These results suggest that sesquiterpene lactones have anti-gout activity through the inflammation, pain, and oxidative stress pathways.Item Surface modification of Ti–30Ta alloy by deposition of P(VDF-TrFE)/BaTiO3 coating for biomedical applications.(2022) Ribeiro, Larissa Mayra Silva; Simões, Luziane Aparecida Costa da Rosa; Soares, Melina Espanhol; Teles, Vinícius Carvalho; Ribeiro, Tainara Aparecida Nunes; Capellato, Patrícia; Fré, Lucas Victor Benjamim Vasconcelos; Kuffner, Bruna Horta Bastos; Saddow, Stephen Edward; Sachs, Daniela; Claro, Ana Paula Rosifini Alves; Gimenes, RossanoThis study aims to promote an adequate methodology for coating an experimental Ti-30Ta alloy with P(VDF-TrFE)/BaTiO3. The combination of a copolymer with a ceramic has not been used until now. Ti-30Ta is an excellent choice to replace current alloys in the global market. The composite deposition on the Ti-30Ta substrate was performed by a spray coating process and at low temperature using two different surface modifications: surface acidic etching and surface polishing. Characterization was divided into four areas: (I) the substrate surface treatments used and their influences on the adhesion process were evaluated using surface energy, wettability, and roughness analyses; (II) the properties of the composite film, which were carried out using X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TG), and differential scanning calorimetry (DSC); (III) the study of the adhesion of the film on the substrate, which was performed by a scratch test; (IV) the final product, which was evaluated to determine the surface properties after the coating process. Biofilm formation using Staphylococcus aureus and Staphylococcus epidermidis strains and a hemocompatibility test were performed as biological assays. The results indicated that the P(VDF-TrFE)/BaTiO3 film showed high thermal stability (up to ≈450 ◦C); the FTIR and DSC tests indicated the presence of the β phase, which means that the material presents a piezoelectric nature; and the scratch test showed that the samples with the polish treatment provided a better adhesion of the film with an adhesion strength of ~10 MPa. From the SEM analysis, it was possible to determine that the spray deposition coating process resulted in a well-applied film as evidenced by its homogeneity. Microbiological tests showed that for Staphylococcus aureus, the bacterial growth in the coated Ti-30Ta presented no significant differences when compared to the alloy without coating. However, for Staphylococcus epidermidis, there was considerable growth on the coated Ti-30Ta, when compared to the non-coated alloy, indicating that the film surface may have favored bacterial growth. The hemolysis assay showed that the coated material presents hemocompatible characteristics when in contact with blood cells. The results obtained indicate that the Ti-30Ta alloy coated with P(VDFTrFE)/BaTiO3 is a promising alternative for implant applications, due to its biocompatible properties, simplicity, and low cost.