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Int Immunopharmacol ; 26(1): 194-202, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25843255

RESUMO

Guggulsterone (GS), a plant steroid and a compound found at high levels in Commiphora myrrha, exhibits anti-inflammatory, anti-cancer, and cholesterol-lowering effects. However, the potential of GS to ameliorate acute pancreatitis (AP) is unknown. The aim of this study was to evaluate the effects of GS on cerulein-induced AP. AP was induced by intraperitoneally injecting supramaximal concentrations of the stable cholecystokinin analog cerulein (50 µg/kg) hourly for 6 h. In the GS-treated group, GS was administered intraperitoneally (10, 25, or 50mg/kg) 1 h before the first cerulein injection. Mice were sacrificed 6 h after the final cerulein injection. Blood samples were collected to measure serum lipase levels and evaluate cytokine production. The pancreas and lung were rapidly removed for morphologic and histological examinations, flow cytometry analysis, myeloperoxidase (MPO) assay, and real-time reverse transcription-polymerase chain reaction analysis. Pre-treatment with GS attenuated cerulein-induced histological damage, reduced pancreas weight/body weight ratio, decreased serum lipase levels, inhibited infiltrations of macrophages and neutrophils, and suppressed cytokine production. Additionally, GS treatment suppressed the activation of extracellular signal-regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) in the pancreas in cerulein-induced pancreatitis. In conclusion, our results suggest that GS attenuates AP via deactivation of ERK and JNK.


Assuntos
Anti-Inflamatórios/uso terapêutico , Ceruletídeo/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Pancreatite/tratamento farmacológico , Pregnenodionas/uso terapêutico , Doença Aguda , Animais , Anti-Inflamatórios/administração & dosagem , Western Blotting , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Ensaio de Imunoadsorção Enzimática , Feminino , Injeções Intraperitoneais , Lipase/sangue , Camundongos Endogâmicos C57BL , Pâncreas/efeitos dos fármacos , Pâncreas/imunologia , Pâncreas/patologia , Pancreatite/enzimologia , Pancreatite/imunologia , Pregnenodionas/administração & dosagem
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