Anti-inflammatory and antioxidant effects of umbelliferone in chronic alcohol-fed rats

BACKGROUND/OBJECTIVES: Inflammation is associated with various types of acute and chronic alcohol liver diseases. In this study, we examined whether umbelliferone (7-hydroxycoumarin, UF) ameliorates chronic alcohol-induced liver damage by modulating inflammatory response and the antioxidant system. METHODS: Rats were fed a Liber-Decarli liquid diet containing 5% alcohol with or without UF (0.05 g/L) for 8 weeks, while normal rats received an isocaloric carbohydrate liquid diet. RESULTS: Chronic alcohol intake significantly increased serum tumor necrosis factor-alpha (TNF-alpha) and interleukin 6 levels and decreased interleukin 10 level; however, UF supplementation reversed the cytokines related to liver damage. UF significantly suppressed hepatic lipopolysaccharide binding protein, toll-like receptor 4 (TLR4), nuclear factor kappa B, and TNF-alpha gene expression increases in response to chronic alcohol intake. Masson's trichrome staining revealed that UF improved mild hepatic fibrosis caused by alcohol, and UF also significantly increased the mRNA expressions and activities of superoxide dismutase and catalase in liver, and thus, decreased lipid peroxide and mitochondrial hydrogen peroxide levels. CONCLUSIONS: The findings of this study indicate that UF protects against alcohol-induced liver damage by inhibiting the TLR4 signaling pathway and activating the antioxidant system.

Effect of Fermented Yacon (Smallanthus Sonchifolius) Leaves Tea on Blood Glucose Levels and Glucose Metabolism in High-Fat Diet and Streptozotocin-Induced Type 2 Diabetic Mice

The aim of this study was to investigate the hypolgycemic activity of water extract of fermented yacon (Smallanthus sonchifolius) leaves tea (Yacon LWE) in high-fat diet (HFD)/streptozotocin (STZ)-induced diabetic mice. Male ICR mice were fed with a HFD (37% calories from fat) for 4 weeks prior to intraperitoneal injection with STZ (100 mg/kg body weight). Diabetic mice were supplemented with two doses of Yacon LWE (0.16% and 0.8%, wt/wt) for 6 weeks. The supplementation of high-dose Yacon LWE significantly lowered blood glucose levels and plasma ALT and AST activities compared with the control group. High-dose Yacon LWE also improved the insulin tolerance without any changes in plasma and pancreatic insulin concentrations in HFD/STZ-induced diabetic mice. Yacon LWE supplementation increased the insulin staining of pancreatic beta-cells in a dose-dependent manner. Both 0.16% and 0.8% of Yacon LWE significantly elevated plasma leptin concentration, hepatic glucokinase activity and glucokinase/glucose-6-phosphatase ratio compared with the control group. However, glycosylated hemoglobin concentration was not different among the groups. These results suggest that high-dose Yacon LWE lowers the blood glucose level partly by enhancing insulin sensitivity and hepatic glucose metabolism in type 2 diabetic mice.

Effect of Young Barley Leaf on Lipid Contents and Hepatic Lipid-Regulating Enzyme Activities in Mice Fed High-Fat Diet

This study was conducted to investigate the effects of powdered young barley leaf and its water extract on body weight and lipid metabolism in high-fat fed mice. Male mice were divided into normal group, high-fat (HF) group, highfat group supplemented with powdered young barley leaf (HF-YBL) and high-fat group supplemented with water extract of the powdered young barley leaf (HF-WYBL). The powdered young barley leaf or its water extract was added to a standard diet based on 1% dried young barley leaf (1 g YBL/100 diet and 0.28 g WYBL/100 g diet) for 8 weeks. Supplementation of YBL and WYBL significantly reduced body weight and epididymal adipose tissue weight in highfat fed mice. Food intake and daily energy intake were significantly lower in the YBL group than in the HF group. After 8 weeks, plasma triglyceride and cholesterol concentrations were significantly higher in the HF group than in the Normal group; however, both YBL and WYBL significantly lowered those of the high-fat fed mice. The ratio of HDL-cholesterol/ total cholesterol of the YBL and WYBL groups were significantly elevated compared to that of HF group. Both YBL and WYBL significantly increased fecal excretion of triglyceride in high-fat fed mice, whereas they did not affect fecal cholesterol concentration. The triglyceride levels of liver, adipose tissue and heart were significantly lower in the YBL and WYBL groups than in the HF group. Supplementation of WYBL also lowered the kidney triglyceride and heart cholesterol concentrations compared to those of HF group. Hepatic lipid regulating enzyme activities, fatty acid synthase, HMG-CoA reductase and acyl-coenzyme A: cholesterol acyltransferase, were significantly lower in the YBL and WYBL groups than in the HF group. Accordingly, these results suggest that YBL and WYBL improve plasma and organ lipid levels partly by increasing fecal lipid excretion and inhibiting fatty acid and cholesterol biosynthesis in the liver.

Effect of Korean Traditional Tea Materials Water Extract on Hepatic Oxygen Free Radical Generating and Scavenging Enzyme Activities in Lead Administered Rats

This study was designed to test the effect of Korean traditional tea materials on oxygen-free radical metabolism in lead (Pb) -administered rats. Male rats were divided into normal, Pb-control (Pb-Con) and Pb-water extract of green tea (Camellia sinensis; GT) , persimmon leaf (Diospyros kaki; PL) , safflower seed (Carhamus tinctorius: SS) , Du-Zhong (Eucommia ulmoides; EU) groups, respectively. Pb intoxication was induced by administration of lead acetate (25 mg/kg. B.W., oral) weekly. The extract was administered based on 1.26 g of raw material/kg B.W./day for 4 weeks. When the GT, PL, SS and EU were supplemented to the Pb-administered rats, hepatic lipid peroxide levels were significantly lower compared to the Pb-Con group. Hepatic cytochrom P-450 content and aminopyrine N-demethylase activity was lower in the Pb-Con group than in the normal group, whereas xanthine oxidase activity was significantly elevated in Pb-administered rats. The water extract of GT, PL, SS and EU supplementation attenuated changes in enzyme activities generating reactive oxygen species in the liver. Hepatic superoxide dismutase, catalase and glucose 6-phosphate dehydrogenase activities were significantly higher in the Pb-Con group than in the normal group, while monoamine oxidase activity also tended to increase in the Pb-administered rats. However, glutathione peroxidase and glutathione S-transferase activities, and glutathione content significantly decreased through Pb intoxication. The supplementation of GT, PL, SS and EU induced alleviation changes of hepatic antioxidant enzyme activity.