RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cecropia Loefl. species (Urticaceae) are widely spread across the rainforest in tropical and subtropical regions of Central and South America. Inhabitants of different regions of Brazil employ leaves, fruits and sprouts of Cecropia hololeuca Miq. mainly as anti-inflammatory, anti-asthmatic, expectorant, fever suppressant, and against cough. AIM OF THE STUDY: To evaluate the antinociceptive and anti-inflammatory activities of an aqueous leaf extract of C. hololeuca in a murine model of zymosan-induced arthritis (ZIA) and characterize compounds contributing to these effects. MATERIALS AND METHODS: The crude aqueous extract of C. hololeuca (CAE) was obtained by infusion, screened for antinociceptive and anti-inflammatory activities, and fractionated (solvent partition; RP-2 and Sephadex G-25 column chromatography), yielding fractions that were chemically and pharmacologically investigated. TLC, HPLC-DAD, HPLC-DAD-ESI-MS/MS and NMR analyses were peformed. The antinociceptive activity was assessed by means of acetic acid-induced writhing, hot-plate and rota-rod tests. ZIA was used to evaluate the anti-arthritic activity of oral treatment with CAE, butanolic (BF) and aqueous fraction (AF), as well as the fractions obtained from BF (F2, F2-A and F2-B). Rutin, a flavonoid found in C. hololeuca, was also tested. Mechanical hypernociception, joint edema, local neutrophil recruitment and articular TNF-α quantification were performed to measure the severity of arthritis and identify the anti-inflammatory potential of C. hololeuca. RESULTS: CAE (0.03-1 g/kg, p.o.) showed a dose-related inhibitory effect on acetic acid-induced writhing test, but did not change the pain latency in the hotplate test, nor the first fall time on the rota-rod test. In addition, CAE (1 g/kg, p.o.) inhibited by 65% the mechanical hypernociception, 46% the joint edema, 54% the neutrophil recruitment and 53% the articular TNF-α concentration levels in ZIA. BF (0.4 g/kg, p.o.), AF (0.6 g/kg), F2 (0.1 g/kg) and F2-A (0.045 g/kg), but not F2-B (0.055 g/kg), inhibited the mechanical hypernociception, joint edema and neutrophil recruitment in ZIA. Rutin (0.001-0.03 g/kg, p.o.) produced dose-related inhibitory effects in the mechanical hypernociception, joint edema and neutrophil recruitment, and at 0.03 g/kg also inhibited articular TNF-α synthesis after intra-articular zymosan injection. Isoorientin, isovitexin, rutin and isoquercitrin were identified in the most active fraction (F2-A), along with luteolin and apigenin derivatives, tentatively identified as isoorientin-2â³-O-glucoside and isovitexin-2â³-O-glucoside. CONCLUSION: This study corroborates the popular use by oral route of aqueous preparations of C. hololeuca against joint inflammatory disorders, such as rheumatoid arthritis. Our results demonstrated for the first time that oral administration of rutin shows antinociceptive and anti-inflammatory effects in ZIA, indicating that this flavonoid is one of the immunomodulatory compounds involved in the anti-arthritic activity of C. hololeuca.
Assuntos
Analgésicos/administração & dosagem , Anti-Inflamatórios/administração & dosagem , Artralgia/prevenção & controle , Artrite Experimental/prevenção & controle , Cecropia , Flavonoides/administração & dosagem , Articulações/efeitos dos fármacos , Dor Nociceptiva/prevenção & controle , Extratos Vegetais/administração & dosagem , Rutina/administração & dosagem , Administração Oral , Analgésicos/isolamento & purificação , Animais , Anti-Inflamatórios/isolamento & purificação , Artralgia/induzido quimicamente , Artralgia/metabolismo , Artralgia/fisiopatologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Artrite Experimental/fisiopatologia , Cecropia/química , Citocinas/metabolismo , Precursores Enzimáticos , Flavonoides/isolamento & purificação , Mediadores da Inflamação/metabolismo , Articulações/metabolismo , Articulações/fisiopatologia , Masculino , Camundongos , Infiltração de Neutrófilos/efeitos dos fármacos , Dor Nociceptiva/induzido quimicamente , Dor Nociceptiva/metabolismo , Dor Nociceptiva/fisiopatologia , Limiar da Dor/efeitos dos fármacos , Extratos Vegetais/isolamento & purificação , Rutina/isolamento & purificaçãoRESUMO
(E)-methyl isoeugenol (MIE) is a natural food flavour that constitutes 93.7% of an essential oil from Pimenta pseudocaryophyllus leaf. The leaf extracts of this species are used as a calming agent. As a ubiquitous food additive, the application of MIE for treating mood disorders appears to be globally attractive. Hence, we sought to evaluate general pharmacological activities, anticonvulsant, anxiolytic and antidepressant effects and the possible mechanisms of MIE actions. Administration of MIE was carried out prior to the exposure of a male Swiss mice to general behavioural tests, barbiturate sleep, PTZ-induced convulsion, light dark box (LDB), elevated plus maze (EPM), wire hanging, open field (OF) and forced swimming test (FST). The involvement of monoamine system was studied by mice pretreatment with WAY100635 (antagonist of 5-HT1A), α-methyl-p-tyrosine (AMPT; depletor of catecholamine) or p-chlorophenylalanine (PCPA; depletor of serotonin storage). There was no record of neurotoxic effect or animal's death during the course of general pharmacological tests. MIE at 250 and 500 mg kg(-1) potentiated the hypnotic effect of sodium pentobarbital. However, MIE did not protect against PTZ-induced convulsion. Except for MIE at 500 mg kg(-1), parameters evaluated in the LDB, EPM and OF demonstrated an anxiolytic like property of MIE. This effect was blocked by WAY100635 pretreatment. MIE at 500 mg kg(-1) elicited a reduction in locomotor activity of the mice in the OF. Anti-immobility effect of MIE 250 mg kg(-1) in the FST suggested an antidepressive like property. Unlike AMPT, pretreatment with PCPA reversed the antidepressant like effect of MIE. Our findings demonstrated anxiolytic and antidepressant like properties of (E)-methyl isoeugenol and suggested the participation of serotonergic pathways.
Assuntos
Anisóis/farmacologia , Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Aromatizantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Relação Dose-Resposta a Droga , Fenclonina/efeitos adversos , Masculino , Camundongos , Condicionamento Físico Animal , Piperazinas/efeitos adversos , Piridinas/efeitos adversos , Serotonina/sangue , Antagonistas da Serotonina/efeitos adversos , alfa-Metiltirosina/efeitos adversosRESUMO
Kalanchoe pinnata (KP) is popularly used for treating inflammatory diseases. This study investigated the antinociceptive, antiedematogenic, and anti-inflammatory potential of the subcutaneous administration of KP flower aqueous extract (KPFE), its ethyl acetate (EtOAcF) and butanol (BuOHF) fractions, and the main KP flavonoid [quercetin 3-O-α-L-arabinopyranosyl (1 â 2) α-L-rhamnopyranoside] (KPFV) in mice, as well as its possible mechanisms of action. KPFE (30-300 mg/kg) and KPFV (1-10 mg/kg) inhibited the acetic acid-induced writhing (ID50 = 164.8 and 9.4 mg/kg, resp.). KPFE (300 mg/kg), EtOAcF (12 mg/kg), BuOHF (15 mg/kg), or KPFV (0.3-3.0 mg/kg) reduced leukocyte migration on carrageenan-induced pleurisy (ID50 = 2.0 mg/kg for KPFV). KPFE (3-30 mg/kg) and KPFV (0.3-3.0 mg/kg) reduced the croton oil-induced ear edema (ID50 = 4.3 and 0.76 mg/kg, resp.). KPFE and KPFV reduced the TNF-α concentration in the pleural exudates on carrageenan-induced pleurisy test. Moreover, KPFV inhibited COX-1 (IC50 = 22.1 µg/mL) and COX-2 (IC50 > 50 µg/mL). The selectivity index (COX-1IC50 /COX-2IC50 ) was <0.44. These results indicate that KPFE and KPFV produced antinociceptive, antiedematogenic, and anti-inflammatory activities through COX inhibition and TNF-α reduction, revealing that the main flavonoid in KP flowers and leaves plays an important role in the ethnomedicinal use of the plant.
RESUMO
Spiranthera odoratissima A. St.-Hil., 'manacá', is a medicinal species used in Brazil, especially in central region, for the treatment of several diseases such as pain and inflammation. In this study, the methanol/aqueous phase of the ethanol extract of the leaves of 'manacá' (MAP), at the doses of 50, 150 and 500 mg/kg was used to evaluate the anti-inflammatory and/or antinociceptive effects and the possible anti-inflammatory mechanism. The antinociceptive and anti-inflammatory activities of MAP were assessed using formalin test, carrageenan-induced paw oedema. The myeloperoxidase activity, capillary permeability, leukocyte migration and tumour necrosis factor alpha (TNF-α) levels were evaluated in pleural exudate. The MAP reduced the licking time only in the later phase of formalin test, and showed anti-inflammatory activity by reducing the paw oedema, migration cell, myeloperoxidase activity, capillary permeability and TNF-α levels. In conclusion, we confirmed the inflammatory activity of MAP and affirm that this effect involves the reduction of TNF-α level.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Extratos Vegetais/farmacologia , Rutaceae/química , Fator de Necrose Tumoral alfa/metabolismo , Administração Oral , Animais , Anti-Inflamatórios não Esteroides/química , Brasil , Carragenina/efeitos adversos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Leucócitos/efeitos dos fármacos , Camundongos , Peroxidase/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Plantas Medicinais/química , Ratos , Testes de Toxicidade AgudaRESUMO
Bioassay-guided fractionation of the ethanolic extract of Pterodon emarginatus Vogel stem bark (EtEx) resulted in the isolation and characterization of lupeol and betulin. Their structures were elucidated by spectroscopic methods including IR, (1)H-NMR, (13)C-NMR and comparison with literature values. This study showed the anti-inflammatory activity of EtEx, the hexane (HexL) and dichloromethane (DichL) layers, and lupeol and betulin. The extract, HexL, DichL, lupeol and betulin were able to inhibit acetic acid-induced writhing. In the formalin test, EtEx decreased licking time only in the second phase characterizing anti-inflammatory activity. In the oil-induced ear oedema test, EtEx, lupeol and betulin decrease edema formation. In conclusion, EtEx has antinociceptive effects arising from anti-inflammatory activity; this activity could be due to the presence of lupeol and betulin.
Assuntos
Anti-Inflamatórios/farmacologia , Etanol/química , Fabaceae , Inflamação/prevenção & controle , Triterpenos Pentacíclicos/farmacologia , Extratos Vegetais/farmacologia , Solventes/química , Triterpenos/farmacologia , Ácido Acético , Analgésicos/química , Analgésicos/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Fracionamento Químico , Óleo de Cróton , Modelos Animais de Doenças , Fabaceae/química , Formaldeído , Hexanos/química , Inflamação/induzido quimicamente , Espectroscopia de Ressonância Magnética , Masculino , Cloreto de Metileno/química , Camundongos , Estrutura Molecular , Dor/induzido quimicamente , Dor/prevenção & controle , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/isolamento & purificação , Casca de Planta , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Caules de Planta , Triterpenos/química , Triterpenos/isolamento & purificaçãoRESUMO
This study was performed to determine the antinociceptive and anti-inflammatory activities of ethanolic extract of Lafoensia pacari A. St.-Hil. (PEtExt) stem bark and its fractions using various animal models such as acetic acid-induced abdominal writhing, formalin-induced pain and croton oil-induced ear edema tests. The PEtExt inhibited the acetic acid-induced abdominal writhing, reduced the pain reaction time on both phases of the formalin test and decreased the edema in a dose-dependent manner. Pre-treatment with naloxone did not reverse the antinociceptive effect. Only the ethyl acetate fraction showed antinociceptive and anti-inflammatory effects. Our results also showed that this extract contains compounds with analgesic action independent of anti-inflammatory activity.
Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Ácido Elágico/farmacologia , Lythraceae/química , Dor/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Acetatos/química , Ácido Acético/toxicidade , Analgésicos/química , Animais , Masculino , Camundongos , Estrutura Molecular , Dor/induzido quimicamente , Extratos Vegetais/químicaRESUMO
chá das cascas Croton cajucara Benth (sacaca) é indicado na medicina popular da região Amazônica para doenças que envolvem dor ou processos inflamatórios. Estudos farmacológicos com os compostos terpenóides isolados das cascas da planta, revelaram atividades antinociceptiva e antiinflamatória sem entretanto ter sido explicado a utilização do chá. Este trabalho investigou em camundongos, a atividade antinociceptiva e antiinflamatória do extrato aquoso (EA) das cascas do Croton cajucara, procurando validar o uso do chá. Alem disso, com padrões dos terpenóides trans-desidrocrotonina (DCTN) e ácido acetil aleuritólico (AAA), comparamos e analisamos a participação destes compostos nos efeitos do extrato aquoso. O EA foi purificado para a obtenção de frações contendo ou não compostos terpenóides. As atividades destas frações foram monitoradas com testes farmacológicos para dor e inflamação. As cascas do caule do Croton cajucara (sacaca) foram coletadas em Jacundá Estado do Pará. O pó obtido das cascas secas e trituradas foi utilizado no prepar do EA a 2 por cento (70§C), que após liofilizado, apresentou rendimento de 10 por cento. O particionamento do EA em n-butanol e água, forneceu as frações BUOH e H2O, que após liofilizadas apresentaram rendimento de 14 por cento. O monitoramento farmacológico indicou maior efeito antinociceptivo na fração H2O. - Na fração H2O não foram detectados compostos terpenóides. - A fração H2O foi purificada por partição em solventes orgânicos de polaridades crescentes (diclorometano, metanol e água), obtendo-se 5 frações. O efeito de antinocicepção foi mantido na fração denominada F3 (rendimento de 9 por cento). - A partição do EA em n-hexano, diclorometano e metanol, forneceu 40 frações untadas por similaridade em cromatografia de camada fina (TLC). As frações 37 à O foram semelhantes à F3, com rendimento de 22 por cento. Análises por cromatografia líquida de alta eficiência analítica confirmaram a semelhança entre as frações, bem mo à ausência do composto trans-desidrocrotonina na fração F3. O espectro da ressonância magnética nuclear protônica e analises específicas m TLC da F3 mostraram a presença de 4 açucares, de 2 aminoácidos e de alcalóides, sendo identificada a n-metiltirosina. No modelo de nocicepção químico, o pré-tratamento (60 min) de amundongos com o EA (O, 1 a l g/kg, p.o.) e a fração F3 (3 a 30 mg/kg. p.o.) obtidos as cascas do Croton cajucara inibiram de maneira...(au)