Browsing by Author "Bernardes, Ana Catharina Fernandes Pereira Ferreira"

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    Avaliação dos efeitos de lactonas sesquiterpênicas na hiperuricemia, excreção do ácido úrico, estresse oxidativo e artrite gotosa.
    (2018) Bernardes, Ana Catharina Fernandes Pereira Ferreira; Guimarães, Dênia Antunes Saúde; Márcio de Matos Coelho; Cardoso, Leonardo Máximo; Guimarães, Dênia Antunes Saúde
    A gota é uma artrite inflamatória aguda causada pela deposição de cristais de urato monossódico nas articulações. A elevação do ácido úrico no sangue pode ser decorrente a vários fatores. As lactonas sesquiterpênicas são substâncias de ocorrência em espécies do gênero Lychnophora (arnica brasileira). O grupo de pesquisa do LAPLAMED/CiPharma/EF/UFOP vem trabalhando há alguns anos com as lactonas sesquiterpênicas e reuniu volume considerável de dados que justificam a seleção destas substâncias como candidatas ao desenvolvimento de fármacos antigota. Estudos prévios realizados por este grupo demonstraram que licnofolida, eremantolida C e goiazensolida promoveram a redução das concentrações séricas de ácido úrico em camundongos Swiss. Entretanto, o mecanismo de ação para a atividade anti-hiperuricêmica não foi totalmente elucidado. A inflamação nas articulações gera um estresse oxidativo nas células de defesa, liberando mediadores pró-inflamatórios. O controle terapêutico da gota consiste em tratar as crises inflamatórias agudas e reduzir os níveis séricos de ácido úrico. Há um número limitado de medicamentos utilizados na prática clínica da gota e eles possuem efeitos adversos severos. Novas opções terapêuticas são necessárias para o tratamento desta patologia. Objetivando avaliar os mecanismos pelos quais as lactonas sesquiterpênicas exercem as ações farmacológicas descritas, o presente estudo avaliou a ação anti-hiperuricêmica, uricosúrica e de inibição da xantina oxidase de licnofolida, eremantolida C e goiazensolida em ratos Wistar além da ação antiinflamatória, antinociceptiva e antioxidante em camundongos C57BL/6. A metodologia do primeiro modelo animal consistiu em tratar ratos hiperuricêmicos com os medicamentos usados clinicamente no tratamento da gota e com as lactonas sesquiterpênicas. O ácido úrico foi dosado no sangue e urina dos ratos, e o fígado retirado para dosagem da atividade residual da enzima xantina oxidase hepática. As lactonas sesquiterpênicas apresentaram atividade anti-hiperuricêmica nas doses de 5 e 10 mg/kg, e ação uricosúrica e/ou inibitória da atividade da xantina oxidase hepática, dependendo da dose. A ação uricosúrica de goiazensolida e licnofolida foi observada na dose de 5 mg/kg. Goiazensolida e licnofolida na dose de 10 mg/kg demonstraram efeitos uricosúricos e de inibição da xantina oxidase, assim como a eremantolida C nas doses de 5 e 10 mg/kg. No segundo modelo experimental, camundongos da XI linhagem C57BL/6 com artrite induzida por MSU na articulação tibiofemoral foram tratados com indometacina e a vitamina C como controles anti-inflamatório e antioxidante, respectivamente, além das lactonas sesquiterpênicas. A nocicepção foi avaliada antes e após a indução da inflamação e tratamento. O líquido articular foi removido para análise da migração de neutrófilos e o tecido periarticular removido para dosagem das enzimas SOD e CAT; além das citocinas IL-1β e TNF-α. As três lactonas sesquiterpênicas foram eficazes como antinociceptivas e antioxidantes. O efeito anti-inflamatório ocorreu devido a inibição da migração de neutrófilos e inibição da produção de TNF-α. Sendo assim, licnofolida, eremantolida C e goiazensolida são candidatas promissoras para o desenvolvimento de fármacos para o tratamento da inflamação, hiperuricemia e gota.
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    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 Saúde
    Ethnopharmacological 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.
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    Effects of the aqueous extract from Tabebuia roseoalba and phenolic acids on hyperuricemia and inflammation.
    (2017) Ferraz Filha, Zilma Schimith; Ferrari, Fernanda Cristina; Araújo, Marcela Carolina de Paula Michel; Bernardes, Ana Catharina Fernandes Pereira Ferreira; Guimarães, Dênia Antunes Saúde
    Tabebuia species (Bignoniaceae) have long been used in folk medicine as anti-inflammatory, antirheumatic, antimicrobial, and antitumor. The aim of this study was to investigate if aqueous extract from the leaves (AEL) of Tabebuia roseoalba (Ridl.) Sandwith, Bignoniaceae, and its constituents could be useful to decrease serum uric acid levels and restrain the gout inflammatory process. HPLC analysis identified caffeic acid and chlorogenic acid in AEL. Antihyperuricemic effects and inhibition of liver XOD (xanthine oxidoreductase) by AEL and identified compounds were evaluated in hyperuricemic mice. Anti-inflammatory activity was evaluated on MSU (monosodium urate) crystal-induced paw edema. In addition, AEL antioxidant activity in vitro was evaluated. AEL, caffeic, and chlorogenic acids were able to reduce serum uric acid levels in hyperuricemic mice probably through inhibition of liver xanthine oxidase activity and significantly decreased the paw edema induced by MSU crystals. AEL showed significant antioxidant activity in all evaluated assays. The results show that the AEL of Tabebuia roseoalba can be a promising agent for treatment for gout and inflammatory diseases. We suggest that caffeic and chlorogenic acids may be responsible for the activities demonstrated by the species.
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    In vivo anti-hyperuricemic activity of sesquiterpene lactones from Lychnophora species.
    (2019) Bernardes, Ana Catharina Fernandes Pereira Ferreira; Coelho, Grazielle Brandão; Araújo, Marcela Carolina de Paula Michel; Guimarães, Dênia Antunes Saúde
    Hyperuricemia is the main cause of gout, an inflammation induced by uric acid deposition in joints. Drugs available present side effects, so there is a need for new treatment alternatives. Lychnophora species are used in folk medicine to treat inflammation, rheumatism and muscle pain. Goyazensolide (10 mg/kg), eremantholide C (25 mg/kg) and lychnopholide (25 mg/kg), sesquiterpene lactones isolated from Lychnophora species were previously studied and showed anti-hyperuricemic effects in mice. However, the mechanisms of this effect were not elucidated. The methodology of this study consisted in treatment of hyperuricemic-induced rats, and comparison between control groups, clinically used anti-hyperuricemic drugs and sesquiterpene lactones. Urine and blood were collected for uric acid quantification. Xanthine oxidase inhibition was measured in liver homogenates. Results showed that all evaluated sesquiterpene lactones presented anti-hyperuricemic activity at the doses of 5 and 10 mg/kg and can act through one or both mechanisms, depending on the dose administrated. Goyazensolide and lychnopholide at dose of 5 mg/kg showed important uricosuric effect. Goyazensolide and lychnopholide at dose of 10 mg/kg, and eremantholide C (5 and 10 mg/kg) presented notable inhibition of hepatic xanthine oxidase activity and uricosuric effect. Thus, these sesquiterpene lactones are promising hypouricemic agent to treat hyperuricemia and gout.
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    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 Saúde
    Ethnopharmacological 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.
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    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 Saúde
    Ethnopharmacological 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.