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Int Immunopharmacol ; 95: 107471, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33756231

RESUMO

Alcoholic liver disease (ALD) is the most common chronic liver disease worldwide. Currently, there is no definitive treatment for alcohol-induced liver injury (ALI). Inflammatory response and oxidative stress play a crucial role in ALI. Cyclooxygenase 2 (COX-2) can be induced by inflammation and it has been reported that the enhanced expression of COX-2 in alcoholic liver injury. Rutaecarpine (RUT) was extracted from evodia rutaecarpa. RUT has a wide range of pharmacological activities. In order to increase its anti-inflammatory activity, our group introduced sulfonyl group to synthesized the 3-[2-(trifluoromethoxy)benzenesulfonamide]-rutaecarpine (3-B-RUT). In this study, we explored the protective effect of 3-B-RUT on alcoholic liver injury in vivo and in vitro and preliminarily explore its mechanism. Mice ALI model was established according to the chronic-plus-binge ethanol model. Results showed that 3-B-RUT (20 µg/kg) attenuated alcohol-induced liver injury and suppressed liver inflammation and oxidative stress, and the effect was comparable to RUT (20 mg/kg). In vitro results are consistent with in vivo results. Mechanistically, the 3-B-RUT might suppress inflammatory response and oxidative stress by regulating activation of NF-κB/COX-2 pathway. In summary, 3-B-RUT, a derivative of RUT, may be a promising clinical candidate for ALI treatment.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Alcaloides Indólicos/uso terapêutico , Hepatopatias Alcoólicas/tratamento farmacológico , Quinazolinas/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Alcaloides Indólicos/farmacologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Hepatopatias Alcoólicas/imunologia , Hepatopatias Alcoólicas/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/antagonistas & inibidores , NF-kappa B/imunologia , Estresse Oxidativo/efeitos dos fármacos , Quinazolinas/farmacologia , Células RAW 264.7
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