RESUMO
Methyl jasmonate (MeJA) is a fatty acid-derived cyclopentanone which shares structural similarities with prostaglandins and has been under study as a promising anti-inflammatory agent. This study investigated the actions of MeJA on systemic inflammation and oxidative status in rats with adjuvant-induced arthritis, a model for rheumatoid arthritis. MeJA (75 to 300 mg·kg-1) was administrated orally during 18 days after arthritis induction with Freund's adjuvant. Articular and systemic inflammation was greatly increased in arthritic rats, likewise the oxidative stress in plasma and liver. The hepatic glucokinase activity and glycolysis were increased in arthritic rats. MeJA decreased most inflammatory parameters and abolished the increased protein carbonylation in plasma and liver, diminished the increased hepatic ROS content, and restored the hepatic GSH/GSSG ratio in arthritic rats. However, the MeJA treatment decreased the hepatic glucokinase activity and glycolysis and stimulated mitochondrial ROS production in healthy and arthritic rats. Oxygen uptake was increased by MeJA only in livers from treated arthritic rats. This action may bear relation to the increased activity of mitochondrial NADP+-dependent enzymes to provide reducing equivalents for the glutathione cycle. These beneficial effects, however, are associated with a decreased glucose flux through the glycolysis in the liver of arthritic and healthy rats.
Assuntos
Acetatos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Ciclopentanos/uso terapêutico , Fígado/patologia , Oxilipinas/uso terapêutico , Acetatos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Artrite Reumatoide/patologia , Ciclopentanos/farmacologia , Estresse Oxidativo , Oxilipinas/farmacologia , RatosRESUMO
OBJECTIVES: The phytohormone methyl jasmonate (MeJA) has been identified as a vital cell regulator in plants. This substance is analogous to eicosanoids and similar to that of anti-inflammatory prostaglandins. In animals and in animal cells, it displayed an efficient neuroprotective, anti-inflammatory and antioxidant action; while in tumoral strains, it demonstrates a potentially highly attractive mechanism of apoptosis induction through various cellular and molecular mechanisms. The aim of the present review was to explore two new hypotheses that explain the action of MeJA, a lipid phytohormone and its potentially anti-apoptotic mechanism for use as a therapeutic target for future treatment of Inflammatory bowel diseases (IBDs). KEY FINDINGS: Methyl jasmonate is a new candidate for the treatment of IBDs, modulating the expression of the major classes of caspase-type protease families that selectively act on the extrinsic and intrinsic pathways of the apoptotic process. Its action is based on the reduction of the expression in tumour necrosis factor tissue levels and the modulating action of reactive oxygen species production, acting only on the destruction of cells that express the diseased phenotype, and preserving cells that are not transformed. CONCLUSIONS: Methyl jasmonate may represent an alternative for the transduction processes of important signals in the cellular renewal of the intestinal mucosa.
Assuntos
Acetatos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Ciclopentanos/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Oxilipinas/uso terapêutico , Reguladores de Crescimento de Plantas , Acetatos/efeitos adversos , Animais , Anti-Inflamatórios/efeitos adversos , Apoptose/efeitos dos fármacos , Ciclopentanos/efeitos adversos , Fármacos Gastrointestinais/efeitos adversos , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Oxilipinas/efeitos adversos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/metabolismoAssuntos
Aprovação de Drogas , Tratamento Farmacológico/enfermagem , Ácidos Carbocíclicos , Benzoxazinas/uso terapêutico , Compostos de Boro/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Cefalosporinas/uso terapêutico , Ciclopentanos/uso terapêutico , Combinação de Medicamentos , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Guanidinas/uso terapêutico , Humanos , Imidazóis/uso terapêutico , Fragmentos Fc das Imunoglobulinas/uso terapêutico , Interferon beta/uso terapêutico , Isoquinolinas/uso terapêutico , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Polietilenoglicóis/uso terapêutico , Piridinas/uso terapêutico , Quinuclidinas/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Tazobactam , Triazóis/uso terapêutico , Estados Unidos , United States Food and Drug AdministrationRESUMO
The gastric cytoprotective activity of several molecules containing an alpha,beta-unsaturated carbonyl system is reported. We attributed this gastroprotective activity to the presence of a non-hindered Michael acceptor in the molecules assayed and suggested that the mechanism of protection would involve, at least in part, a nucleophilic attack of the sulphydryl group of the gastric mucosa to the beta carbon of the Michael acceptors of the compounds assayed.
Assuntos
4-Butirolactona/análogos & derivados , Antiulcerosos/uso terapêutico , Ciclopentanos/uso terapêutico , Úlcera Gástrica/prevenção & controle , 4-Butirolactona/química , 4-Butirolactona/uso terapêutico , Animais , Antiulcerosos/química , Ciclopentanos/química , Mucosa Gástrica/efeitos dos fármacos , Substâncias Protetoras/química , Substâncias Protetoras/uso terapêutico , Ratos , Ratos Wistar , Úlcera Gástrica/induzido quimicamente , Relação Estrutura-AtividadeRESUMO
In previous reports we attributed the cytoprotective activity of several sesquiterpene lactones to the presence of a nonhindered electrophilic acceptor in their structure. We suggested that the mechanism of protection would be, at least in part, mediated through a reaction between the electrophilic acceptor and the sulfhydryl-containing groups of the mucosa. We report here the gastric cytoprotective effect of simple molecules containing an alpha, beta-unsaturated carbonyl group. In the present paper, we undertake the study of molecular accessibility and molecular shape, in addition to conformational, electronic, and steric factors. Our results helped to establish two important facts connecting chemical structure with cytoprotective effect. Firstly, an adequate molecular accessibility appears to be necessary to produce the biological response, and secondly, the alpha,beta-unsaturated carbonyl system has to be included in a cyclic structure or, at least, in the proximity of a cyclic system.