RESUMO
Gynostemma pentaphyllum is widely used in Asian countries as a herbal medicine to treat dyslipidemia, type 2 diabetes and inflammation. An ethanol extract of G. pentaphyllum lessened obesity by activating AMP-activated protein kinase (AMPK). The levels of damulins A and B, components responsible for AMPK activation in the extract, were increased by autoclaving in a time-dependent manner. Heat-processed G. pentaphyllum extract, actiponin containing damulins A (0.93 %, w/w) and B (0.68 %, w/w), significantly stimulated fat oxidation and glucose uptake via AMPK activation in L6 myotube cells. Oral administration of actiponin to ob/ob mice for 8 weeks decreased body weight gain, liver weight, and blood cholesterol levels with AMPK activation in the soleus muscle. Our results demonstrate the beneficial effect of G. pentaphyllum on improving obesity and have elucidated the underlying molecular mechanisms.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Ativadores de Enzimas/uso terapêutico , Gynostemma/química , Temperatura Alta , Obesidade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Administração Oral , Animais , Linhagem Celular , Modelos Animais de Doenças , Ativadores de Enzimas/administração & dosagem , Ativadores de Enzimas/isolamento & purificação , Ativadores de Enzimas/farmacologia , Glucose/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Musculares/efeitos dos fármacos , Células Musculares/metabolismo , Oxirredução , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Fatores de TempoRESUMO
AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose, lipid, and energy metabolism throughout the body. Activation of AMPK improves metabolic abnormalities associated with metabolic diseases including obesity and type-2 diabetes. The oriental traditional medicinal herbal plant, Gynostemma pentaphyllum, has shown a wide range of beneficial effects on glucose and lipid metabolism. In this study, we found that G. pentaphyllum contains two novel dammarane-type saponins designated as damulin A (1), 2α,3ß,12ß-trihydroxydammar-20(22)-E,24-diene-3-O-[ß-D-glucopyranosyl-(1â2)-ß-D-glucopyranoside], and damulin B (2), 2α,3ß,12ß-trihydroxydammar-20,24-diene-3-O-[ß-D-glucopyranosyl-(1â2)-ß-D-glucopyranoside], that strongly activate AMPK in cultured L6 myotube cells. Damulins A and B also increased ß-oxidation and glucose uptake with increasing GluT4 translocation to the plasma membrane in L6 myotube cells. Taken together our results indicate that activation of AMPK by damulins A and B may contribute to beneficial effect of G. pentaphyllum on glucose and lipid metabolism.