ABSTRACT
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.
Subject(s)
Animals , Antineoplastic Agents, Phytogenic/pharmacology , Blotting, Western , Diabetes Complications/etiology , Diabetes Complications/pathology , Diabetes Complications/prevention & control , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Dyslipidemias/drug therapy , Dyslipidemias/etiology , Dyslipidemias/pathology , Glucokinase/metabolism , Glucose/metabolism , Glucose Transporter Type 2/genetics , Glucose-6-Phosphatase/metabolism , Glycogen/metabolism , Hyperglycemia/complications , Kidney Diseases/etiology , Kidney Diseases/pathology , Kidney Diseases/prevention & control , Male , Mice , Mice, Inbred ICR , Mice, Inbred NOD , Polymers/metabolism , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Triterpenes/pharmacologyABSTRACT
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.