Effects of ursolic acid on glucose metabolism, the polyol pathway and dyslipidemia in non-obese type 2 diabetic mice.

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.

Scopoletin prevents alcohol-induced hepatic lipid accumulation by modulating the AMPK-SREBP pathway in diet-induced obese mice.

OBJECTIVE: This study investigated the effects of scopoletin on alcohol-induced hepatic lipid accumulation in diet-induced obese mice and its mechanism. MATERIAL/METHODS: Alcohol (25% v/v, 5g/kg body weight) was orally administered once a day for 6 weeks to mice fed with a high-fat diet (35%kcal) with or without scopoletin (0.05%, wt/wt). RESULTS: Scopoletin reduced plasma acetaldehyde, fatty acid, total cholesterol, triglyceride and insulin levels, hepatic lipid and droplets and fasting blood glucose levels that were increased by alcohol. Scopoletin significantly activated hepatic AMPK and inhibited ACC and SREBP-1c and the activities of lipogenic enzymes, such as FAS, PAP and G6PD compared to the alcohol control group. Moreover, scopoletin significantly inhibited hepatic CYP2E1 activity and protein levels but elevated the activities of SOD, CAT, GSH-Px and GST and the levels of GSH compared to the alcohol control group. The hepatic lipid peroxide level was significantly lowered by scopoletin supplementation in alcohol-administered obese mice. CONCLUSIONS: Taken together, these results suggested that scopoletin can ameliorate alcohol-induced hepatic lipid accumulation by modulating AMPK-SREBP pathway-mediated lipogenesis in mice fed a high-fat diet.

Platycodi radix saponin inhibits α-glucosidase in vitro and modulates hepatic glucose-regulating enzyme activities in C57BL/KsJ-db/db mice.

This study investigated anti-diabetic activity of a concentrated saponin fraction from Platycodi radix (SK1) in C57BL/KsJ-db/db mice and its underlying mechanism. Mice were fed diet with 0.5 % SK1 (w/w) for 6 weeks. SK1 significantly lowered the blood glucose and glycosylated hemoglobin levels and improved glucose and insulin tolerance. The plasma and pancreatic insulin and C-peptide levels and fecal cholesterol content were increased, whereas plasma urea nitrogen, free fatty acid and triglyceride levels were decreased by SK1 supplementation. Glucokinase (GK) activity in the liver was significantly higher in the SK1 group than the control group, whereas the glucose-6-phosphatase (G6Pase) activity was lower. SK1 significantly down-regulated GK mRNA expression compared to the control group but did not affect G6Pase and glucose transporter 2 mRNA. Phosphoenolpyruvate carboxykinase activity and mRNA levels did not differ between groups. SK1 also markedly inhibited the small intestinal disaccharidases activities compared to those of control db/db mice. Furthermore, SK1 was a more effective α-glucosidase inhibitor than acarbose in vitro. Overall, these findings suggest that SK1 is a potential glucose-lowering agent that functions via inhibition of carbohydrate digestive enzyme activities and modulation of glucose-regulating enzyme activities in db/db mice.

Low doses of curcumin protect alcohol-induced liver damage by modulation of the alcohol metabolic pathway, CYP2E1 and AMPK.

AIMS: This study investigated the hepatoprotective effects of low doses of curcumin against liver damage induced by chronic alcohol intake and a high-fat diet. We also examined several potential underlying mechanisms including action on alcohol metabolism, antioxidant activity, AMPK level and lipid metabolism. MAIN METHOD: Alcohol (25% v/v, 5 g/kg body weight) was orally administered once a day for 6 weeks to mice fed a high-fat diet with or without two different doses of curcumin (0.02% and 0.05%, wt/wt). KEY FINDINGS: Curcumin significantly decreased the plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase activities (p<0.05) and prevented hepatic steatosis compared with the alcohol control group. Curcumin significantly reversed the alcohol-induced inhibition of the alcohol dehydrogenase, aldehyde dehydrogenase 2 and antioxidant enzyme activities as well as the activation of cytochrome P4502E1 and promotion of lipid peroxidation (p<0.05). Curcumin significantly increased the hepatic total AMPK protein level and concomitantly suppressed the fatty acid synthase and phosphatidate phosphohydrolase activities compared with the alcohol control group (p<0.05). Furthermore, curcumin significantly lowered the plasma leptin, free fatty acids and triglycerides levels and hepatic lipid levels (p<0.05). SIGNIFICANCE: These findings indicate that low doses of curcumin may protect against liver damage caused by chronic alcohol intake and a high-fat diet partly by modulating the alcohol metabolic enzyme activity, the antioxidant activity and the lipid metabolism. Therefore, curcumin may provide a promising natural therapeutic strategy against liver disease.