RESUMEN
Nonalcoholic fatty liver disease is the most common chronic disease affecting a wide range of the world's population and associated with obesity-induced metabolic syndrome. It is possibly emerging as a leading cause of life-threatening liver diseases for which a drug with a specific therapeutic target has not been developed yet. Previously, there have been reports on the benefits of Cudrania tricuspidata (CT) for treating obesity and diabetes via regulation of metabolic processes, such as lipogenesis, lipolysis, and inflammation. In this study, we investigated the ameliorative effect of orally administered 0.25% and 0.5% (w/w) CT mixed with high-fat diet (HFD) to C57BL/6J mice for 7 weeks. It was found that body weight, fat mass, hepatic mass, serum glucose level, and liver cholesterol levels were significantly reduced after CT treatment. In CT-treated HFD-fed mice, the mRNA expression levels of hepatic lipogenic and inflammatory cytokine-related genes were markedly reduced, whereas the expression level of epididymal lipogenic genes was increased. The mRNA expression level of beta-oxidation and Nrf-2/HO-1 genes significantly increased in CT-treated obese mice livers. We propose that CT alleviates hepatic steatosis by reducing oxidative stress and inflammation.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Hemo-Oxigenasa 1/metabolismo , Proteínas de la Membrana/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos , Adiposidad/efectos de los fármacos , Animales , Biomarcadores , Glucemia , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Prueba de Tolerancia a la Glucosa , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Lipogénesis/efectos de los fármacos , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Oxidación-Reducción/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/genética , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Bioisosteric analogues of pachastrissamine that contain sulfur and selenium atoms replacing the oxygen in the ring system, were efficiently prepared from a cyclic sulfate intermediate by sequential intermolecular and intramolecular S(N)2 displacement reactions of the dianions. The analogues exhibited cytotoxicities comparable to that of pachastrissamine.