RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Preparation from leaves of Cordia americana have been widely used in traditional medicine in South Brazil to treat wounds and various inflammations. AIM OF THE STUDY: The objective of this work was to identify the effective compounds in the ethanolic extract prepared from the leaves of Cordia americana, which is used in traditional South Brazilian medicine as anti-inflammatory and wound healing remedy. MATERIALS AND METHODS: Isolation and structure elucidation techniques were performed in order to identify the compounds of Cordia americana and HPLC analysis was used for the quantification. The major constituent and the ethanolic extract were investigated for inhibition of 5-lipoxygenase, p38alpha MAPK, TNFalpha release and NF-kappaB as well as in the fibroblast scratch assay. RESULTS: Rosmarinic acid (1) was identified as the major compound with an amount of 8.44% in the ethanolic extract of the leaves of Cordia americana. The ethanolic extract as well as (1) exhibited the highest inhibitory effects on 5-lipoxygenase (IC(50)=0.69 and 0.97microg/mL, resp., IC50 of BWA4C as reference: 0.3microM) and p38alpha (IC50=3.25 and 1.16microg/mL, resp., IC50 of SB203580 as reference: 0.046microM) and moderate inhibitory effects on TNFalpha release. Slight effects were observed in the fibroblast scratch assay. CONCLUSIONS: This study increases our knowledge on the effective compound in Cordia americana and supports its use in traditional medicine. We demonstrated for the first time pharmacological effects of Cordia americana and we provide evidences for a crucial role of rosmarinic acid as the major key player.
Assuntos
Cordia/química , Lipoxigenase/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Araquidonato 5-Lipoxigenase , Brasil , Cinamatos , Depsídeos , Etanol , Inflamação/tratamento farmacológico , Concentração Inibidora 50 , Medicina Tradicional , NF-kappa B/genética , NF-kappa B/metabolismo , Folhas de Planta/química , Fator de Necrose Tumoral alfa/metabolismo , Ácido RosmarínicoRESUMO
AIM OF THE STUDY: n-Hexanic and ethanolic extracts from twelve plants (Brugmansia suaveolens Brecht. et Presl., Eupatorium laevigatum Lam., Galinsoga parviflora Cav., Iresine herbstii Hook., Kalanchöe tubiflora Hamet-Ahti, Petiveria alliacea L., Pluchea sagittalis (Lam.) Cabrera, Piper regnellii DC., Schinus molle L., Sedum dendroideum Moç et Sessé ex DC., Waltheria douradinha St. Hill., Xanthium cavanillesii Schouw.) used in traditional South Brazilian medicine as wound healing agents were investigated in various biological assays, targeting different aspects in this complex process. MATERIALS AND METHODS: The extracts were investigated on NF-kappaB DNA binding, p38alpha MAPK, TNF-alpha release, direct elastase inhibition and its release as well as on caspase-3. Fibroblasts migration to and proliferation into the wounded monolayers were evaluated in the scratch assay, the agar diffusion test for antibacterial and the MTT assay for cytotoxic effects. RESULTS: The hydrophilic extracts from Galinsoga parviflora, Petiveria alliacea, Schinus molle, Waltheria douradinha and Xanthium cavanillesii as well as the lipophilic extract of Waltheria douradinha turned out to be the most active ones. CONCLUSIONS: These results increase our knowledge on the wound healing effects of the investigated medicinal plants. Further studies are necessary to find out the effective secondary metabolites responsible for the observed effects.
Assuntos
Magnoliopsida , Fitoterapia , Extratos Vegetais/farmacologia , Plantas Medicinais , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Brasil , Caspase 3/metabolismo , Linhagem Celular , Citotoxinas/farmacologia , Fibroblastos/efeitos dos fármacos , Humanos , Medicina Tradicional , Camundongos , Testes de Sensibilidade Microbiana , NF-kappa B/genética , NF-kappa B/metabolismo , Elastase Pancreática/metabolismo , Extratos Vegetais/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo , Cicatrização/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Estudou-se o efeito terapêutico da lactona sesquiterpênica (SL), 4,15-Epoxy-miller-9-Z-enolide, na lesão local do envenenamento botrópico experimental. Utilizaram-se três grupos de coelhos inoculados com 1.0µg de veneno de Bothrops alternatus e tratados com solução NaCl (0,85%) (grupo I), SL diluída em glicerol (0,5%) (grupo II) e SL diluída em vaselina (0,5%) (grupo III). Todos os animais foram avaliados nos tempos 30min e 1, 2, 24, 30, 48, 54, 72, 96, 120 e 148h quanto ao grau de edema, diâmetro do halo hemorrágico e presença de necrose local. Os animais do grupo II apresentaram os menores valores de grau de edema e halo hemorrágico com desaparecimento em 54h. Apesar de a necrose ter ocorrido em todos os animais, o diâmetro também foi menor no grupo II, quando comparado com os outros grupos. A SL, extraída da Milleria quinqueflora, possui efeito antiinflamatório, que é importante no tratamento local do envenenamento botrópico.(AU)
Assuntos
Animais , Lactonas/isolamento & purificação , Lactonas/uso terapêutico , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/veterinária , CoelhosRESUMO
Estudou-se o efeito terapêutico da lactona sesquiterpênica (SL), 4,15-Epoxy-miller-9-Z-enolide, na lesão local do envenenamento botrópico experimental. Utilizaram-se três grupos de coelhos inoculados com 1.0æg de veneno de Bothrops alternatus e tratados com solução NaCl (0,85 por cento) (grupo I), SL diluída em glicerol (0,5 por cento) (grupo II) e SL diluída em vaselina (0,5 por cento) (grupo III). Todos os animais foram avaliados nos tempos 30min e 1, 2, 24, 30, 48, 54, 72, 96, 120 e 148h quanto ao grau de edema, diâmetro do halo hemorrágico e presença de necrose local. Os animais do grupo II apresentaram os menores valores de grau de edema e halo hemorrágico com desaparecimento em 54h. Apesar de a necrose ter ocorrido em todos os animais, o diâmetro também foi menor no grupo II, quando comparado com os outros grupos. A SL, extraída da Milleria quinqueflora, possui efeito antiinflamatório, que é importante no tratamento local do envenenamento botrópico.
Assuntos
Animais , Lactonas/isolamento & purificação , Lactonas/uso terapêutico , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/veterinária , CoelhosRESUMO
Investigation of Podachaenium eminens afforded nine sesquiterpene lactones (Sls) from which costunolide, 7-hydroxycostunolide, santamarin as well as 3-chlorodehydroleucodin are new for this plant and 3,4-dehydro-4-dehydroxypodachaenin (= 3-costoyloxydehydroleucodin) is found for the first time in nature. All isolated Sls were studied for their anti-inflammatory activity using the transcription factor NF-kappa B as a molecular target. NF-kappa B is involved in the synthesis of inflammatory mediators, such as cytokines and chemokines. Except for podachaenin, all compounds completely inhibited NF-kappa B DNA binding in an electrophoretic mobility shift assay at concentrations between 5 and 200 microM without showing any cytotoxic effects. 3,4-Epoxydehydroleucodin possessing an alpha-methylene-gamma-butyrolactone and a second reactive structure element by its epoxy ring alpha,beta to a carbonyl group was most active. Although the majority of the Sls tested in this study were monofunctional only low concentrations of 50 microM were often needed for complete inhibition. Possible reasons are discussed for this result.
Assuntos
Asteraceae/química , Lactonas/farmacologia , NF-kappa B/antagonistas & inibidores , Sesquiterpenos/química , Humanos , Células Jurkat , Lactonas/químicaRESUMO
In Central America aerial parts of the Asteraceae Milleria quinqueflora are used in traditional medicine as a remedy for skin infections. Reinvestigation of this plant afforded thirteen sesquiterpene lactones (Sls), three of them are new. All isolated Sls were studied for their anti-inflammatory activity using the transcription factor NF-kappa B as molecular target. NF-kappa B is involved in the synthesis of inflammatory mediators, such as cytokines and chemokines. NF-kappa B DNA binding was inhibited at micromolar concentrations by all Sls.