RESUMO
Ursolic acid (UA) is a pentacyclic triterpenoid compound that naturally occurs in fruits, leaves and flowers of medicinal herbs. This study investigated the dose-response efficacy of UA (0.01 and 0.05%) on glucose metabolism, the polyol pathway and dyslipidemia in streptozotocin/nicotinamide-induced diabetic mice. Supplement with both UA doses reduced fasting blood glucose and plasma triglyceride levels in non-obese type 2 diabetic mice. High-dose UA significantly lowered plasma free fatty acid, total cholesterol and VLDL-cholesterol levels compared with the diabetic control mice, while LDL-cholesterol levels were reduced with both doses. UA supplement effectively decreased hepatic glucose-6-phosphatase activity and increased glucokinase activity, the glucokinase/glucose-6-phosphatase ratio, GLUT2 mRNA levels and glycogen content compared with the diabetic control mice. UA supplement attenuated hyperglycemia-induced renal hypertrophy and histological changes. Renal aldose reductase activity was higher, whereas sorbitol dehydrogenase activity was lower in the diabetic control group than in the non-diabetic group. However, UA supplement reversed the biochemical changes in polyol pathway to normal values. These results demonstrated that low-dose UA had preventive potency for diabetic renal complications, which could be mediated by changes in hepatic glucose metabolism and the renal polyol pathway. High-dose UA was more effective anti-dyslipidemia therapy in non-obese type 2 diabetic mice.
Assuntos
Animais , Antineoplásicos Fitogênicos/farmacologia , Western Blotting , Complicações do Diabetes/etiologia , Complicações do Diabetes/patologia , Complicações do Diabetes/prevenção & controle , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Dislipidemias/tratamento farmacológico , Dislipidemias/etiologia , Dislipidemias/patologia , Glucoquinase/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 2/genética , Glucose-6-Fosfatase/metabolismo , Glicogênio/metabolismo , Hiperglicemia/complicações , Nefropatias/etiologia , Nefropatias/patologia , Nefropatias/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Endogâmicos NOD , Polímeros/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologiaRESUMO
Heat shock proteins (HSPs) are evolutionally conserved from micro organism to mammals and play important roles in many biological processes including thermal tolerance. We isolated a homologue of small HSP26 (sHSP26) from a subtracted cDNA library of heat shock-treated abalone (Haliotis discus hannai). The abalone sHSP26 encompossed 793 nt, including a coding region of 501 nt. The deduced amino acid sequence of the abalone sHSP26 contained well conserved alpha-crystallin domain and showed overall identities of 27-31% with the other species' sHSP proteins. The abalone sHSP26 transcript was induced by heat shock treatment, but not by cold shock treatment.