Seon-Min Jeon

Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice

This study investigated the efficacy of chlorogenic acid on altering body fat in high-fat diet (37% calories from fat) induced-obese mice compared to caffeic acid. Caffeic acid or chlorogenic acid was supplemented with high-fat diet at 0.02% (wt/wt) dose. Both caffeic acid and chlorogenic acid significantly lowered body weight, visceral fat mass and plasma leptin and insulin levels compared to the high-fat control group. They also lowered triglyceride (in plasma, liver and heart) and cholesterol (in plasma, adipose tissue and heart) concentrations. Triglyceride content in adipose tissue was significantly lowered, whereas the plasma adiponectin level was elevated by chlorogenic acid supplementation compared to the high-fat control group. Body weight was significantly correlated with plasma leptin (r=0.894, p<0.01) and insulin (r=0.496, p<0.01) levels, respectively. Caffeic acid and chlorogenic acid significantly inhibited fatty acid synthase, 3-hydroxy-3-methylglutaryl CoA reductase and acyl-CoA:cholesterol acyltransferase activities, while they increased fatty acid beta-oxidation activity and peroxisome proliferator-activated receptors alpha expression in the liver compared to the high-fat group. These results suggest that caffeic acid and chlorogenic acid improve body weight, lipid metabolism and obesity-related hormones levels in high-fat fed mice. Chlorogenic acid seemed to be more potent for body weight reduction and regulation of lipid metabolism than caffeic acid.

Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice.

We investigated the effect of curcumin on insulin resistance and glucose homeostasis in male C57BL/KsJ-db/db mice and their age-matched lean non-diabetic db/+ mice. Both db/+ and db/db mice were fed with or without curcumin (0.02%, wt/wt) for 6 wks. Curcumin significantly lowered blood glucose and HbA 1c levels, and it suppressed body weight loss in db/db mice. Curcumin improved homeostasis model assessment of insulin resistance and glucose tolerance, and elevated the plasma insulin level in db/db mice. Hepatic glucokinase activity was significantly higher in the curcumin-supplemented db/db group than in the db/db group, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly lower. In db/db mice, curcumin significantly lowered the hepatic activities of fatty acid synthase, beta-oxidation, 3-hydroxy-3-methylglutaryl coenzyme reductase, and acyl-CoA: cholesterol acyltransferase. Curcumin significantly lowered plasma free fatty acid, cholesterol, and triglyceride concentrations and increased the hepatic glycogen and skeletal muscle lipoprotein lipase in db/db mice. Curcumin normalized erythrocyte and hepatic antioxidant enzyme activities (superoxide dismutase, catalase, gluthathione peroxidase) in db/db mice that resulted in a significant reduction in lipid peroxidation. However, curcumin showed no effect on the blood glucose, plasma insulin, and glucose regulating enzyme activities in db/+ mice. These results suggest that curcumin seemed to be a potential glucose-lowering agent and antioxidant in type 2 diabetic db/db mice, but had no affect in non-diabetic db/+ mice.

Antioxidative activity of naringin and lovastatin in high cholesterol-fed rabbits

The consumption of a cholesterol-enriched diet increases the degree of lipid peroxidation, which is one of the early processes of atherosclerosis. The aim of this trial was to determine the antioxidative effects of the citrus bioflavonoid, naringin, a potent cholesterol-lowering agent, compared to the cholesterol-lowering drug, lovastatin, in rabbits fed a high cholesterol diet. Male rabbits were served a high-cholesterol (0.5%, w/w) diet or high-cholesterol diet supplemented with either naringin (0.5% cholesterol, 0.05% naringin, w/w) or lovastatin (0.5% cholesterol, 0.03% lovastatin, w/w) for 8 weeks to determine the plasma and hepatic lipid peroxide, plasma vitamin A and E levels, and hepatic hydrogen peroxide levels, along with the hepatic antioxidant enzyme activities and gene expressions. Only the lovastatin group showed significantly lower plasma and hepatic lipid peroxide levels compared to the control group. The naringin supplementation significantly increased the activities of both hepatic SOD and catalase by 33% and 20%, respectively, whereas the lovastatin supplementation only increased the catalase activity by 23% compared to control group. There was no difference in the GSH-Px activities between the various groups. Content of H2O2 in hepatic mitochondria was significantly lower in groups supplemented with lovastatin and naringin than in control group. However, there was no difference in cytosolic H2O2 content in liver between groups. The concentration of plasma vitamin E was significantly increased by the naringin supplementation. When comparing the antioxidant enzyme gene expression, the mRNA expression of SOD, catalase and GSH-Px was significantly up-regulated in the naringin-supplemented group. Accordingly, these results would appear to indicate that naringin, a citrus bioflavonoid, plays an important role in regulating antioxidative capacities by increasing the SOD and catalase activities, up-regulating the gene expressions of SOD, catalase, and GSH-Px, and protecting the plasma vitamin E. In contrast, lovastatin exhibited an inhibitory effect on the plasma and hepatic lipid peroxidation and increased the hepatic catalase activity in high-cholesterol fed rabbits.

Antihyperglycemic and Antioxidant Properties of Caffeic Acid in db/db Mice

This study investigated the blood glucose-lowering effect and antioxidant capacity of caffeic acid in C57BL/KsJ-db/db mice. Caffeic acid induced a significant reduction of the blood glucose and glycosylated hemoglobin levels than the control group. The plasma insulin, C-peptide, and leptin levels in caffeic acid group were significantly higher than those of the control group, whereas the plasma glucagon level was lower. Increased plasma insulin by caffeic acid was attributable to an antidegenerative effect on the islets. Caffeic acid also markedly increased glucokinase activity and its mRNA expression and glycogen content and simultaneously lowered glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities and their respective mRNA expressions, accompanied by a reduction in the glucose transporter 2 expression in the liver. In contrast to the hepatic glucose transporter 2, adipocyte glucose transporter 4 expression was greater than the control group. In addition, caffeic acid significantly increased superoxide dismutase, catalase, and glutathione peroxidase activities and their respective mRNA levels, while lowering the hydrogen peroxide and thiobarbituric acid reactive substances levels in the erythrocyte and liver of db/db mice. These results indicate that caffeic acid exhibits a significant potential as an antidiabetic agent by suppressing a progression of type 2 diabetic states that is suggested by an attenuation of hepatic glucose output and enhancement of adipocyte glucose uptake, insulin secretion, and antioxidant capacity.

Beneficial effects of curcumin on hyperlipidemia and insulin resistance in high-fat–fed hamsters

This study investigated the effect of curcumin (0.05-g/100-g diet) supplementation on a high-fat diet (10% coconut oil, 0.2% cholesterol, wt/wt) fed to hamsters, one of the rodent species that are most closely related to humans in lipid metabolism. Curcumin significantly lowered the levels of free fatty acid, total cholesterol, triglyceride, and leptin and the homeostasis model assessment of insulin resistance index, whereas it elevated the levels of high-density lipoprotein cholesterol and apolipoprotein (apo) A-I and paraoxonase activity in plasma, compared with the control group. The levels of hepatic cholesterol and triglyceride were also lower in the curcumin group than in the control group. In the liver, fatty acid beta-oxidation activity was significantly higher in the curcumin group than in the control group, whereas fatty acid synthase, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and acyl coenzyme A:cholesterol acyltransferase activities were significantly lower. Curcumin significantly lowered the lipid peroxide levels in the erythrocyte and liver compared with the control group. These results indicate that curcumin exhibits an obvious hypolipidemic effect by increasing plasma paraoxonase activity, ratios of high-density lipoprotein cholesterol to total cholesterol and of apo A-I to apo B, and hepatic fatty acid oxidation activity with simultaneous inhibition of hepatic fatty acid and cholesterol biosynthesis in high-fat-fed hamsters.

Alternation of hepatic antioxidant enzyme activities and lipid profile in streptozotocin-induced diabetic rats by supplementation of dandelion water extract

BACKGROUND Dandelion water extract (DWE), an herbal medication, may have an effect on the activity and mRNA expression of hepatic antioxidant enzymes and lipid profile in streptozotocin (STZ)-induced diabetic rats. METHODS Male Sprague-Dawley rats were divided into nondiabetic (control), diabetic, and diabetic-DWE-supplemented groups. Diabetes was induced by injecting streptozotocin (55 mg/kg BW, i.p.) in a citrate buffer. The extract was supplemented in 2.4 g of a DWE/kg diet. RESULTS The DWE supplement significantly decreased the serum glucose concentration in the diabetic rats. The hepatic superoxide dismutase and catalase activities significantly increased and the GSH-Px activity decreased in the diabetic rats, compared with the control group. When the DWE supplement was given to the diabetic rats, the antioxidant enzyme activity reverted to near-control values. However, there was no difference in the mRNA expression concentrations of these enzymes between the groups. With regard to the hepatic lipid peroxidation product, the malondialdehyde (MDA) content was significantly higher in the diabetic group than in the nondiabetic group. However, the DWE supplement lowered the hepatic MDA concentration in the diabetic-induced rats. The DWE supplement also lowered the total cholesterol and triglyceride concentrations in the serum and hepatic tissue, while increasing the serum HDL-cholesterol in the diabetic rats. CONCLUSIONS A DWE supplement can improve the lipid metabolism and is beneficial in preventing diabetic complications from lipid peroxidation and free radicals in diabetic rats.

Effect of rutin and tannic acid supplements on cholesterol metabolism in rats1

Abstract This study was designed to test the lipid-lowering and antioxidative activities of two phenolic compounds, rutin and tannic acid. Three groups of rats were given a semisynthetic diet containing 1 g of cholesterol/kg for 5 wks. The control group only received a high cholesterol diet, whereas the other two groups received a diet including 1 g of rutin or 1 g of tannic acid/kg. The rutin and tannic acid both significantly lowered the plasma lipid and hepatic cholesterol levels compared to those in the control. The hepatic HMG-CoA reductase activity was significantly lower in the tannic acid group than in the rutin group, while the hepatic ACAT activity was significantly lower in both the rutin and tannic groups compared to the control group. The overall potential of the antioxidant system was significantly enhanced by the rutin and tannic acid supplements as the plasma and hepatic TBARS levels were lowered while the hepatic SOD and GSH-Px activities were increased in the high-cholesterol fed rats. Furthermore, these results suggest that the supplementation of rutin and tannic acid promoted the excretion of fecal sterols, thereby leading to a decreased absorption of dietary cholesterol as well as lower plasma and hepatic cholesterol.

Long-term effects of resveratrol supplementation on suppression of atherogenic lesion formation and cholesterol synthesis in apo E-deficient mice

Atherosclerosis is a chronic inflammatory disease of the arteries resulting from interactions between lipids, monocytes, and arterial wall cells. The effects of resveratrol supplements (RV, 0.02% and 0.06% each, w/w) with regard to the modulation of lipid profiles, cholesterol synthesis, and anti-atherogenesis were examined in apo E-deficient (apo E(-/-)) mice fed a normal diet. The concentration of total-cholesterol (total-C) and LDL-cholesterol (LDL-C) in plasma was significantly lower in the resveratrol-supplemented groups compare to the control group over the entire experimental period. The plasma HDL-C concentration was significantly elevated, and the ratio of HDL-C/total-C was significantly higher in the CF and RV groups than in the control group. Plasma paraoxonase (PON) activity was significantly higher in the 0.06% resveratrol group. The hepatic HMG-CoA reductase (HMGR) activity was significantly lower in the clofibrate and resveratrol groups than in the control group. Resveratrol supplements attenuated the presence of atherosclerotic lesions and periarterial fat deposition in the apo E(-/-) mice. The presence of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in atherosclerotic vessels was diminished in the resveratrol-supplemented apo E(-/-) mice. These results provide new insight into the anti-atherogenic and hypocholesterolemic properties of resveratrol in apo E(-/-) mice that were fed a normal diet.

Comparison of antioxidant effects of naringin and probucol in cholesterol-fed rabbits.

BACKGROUND Due to the strong evidence on the involvement of active oxygen species in a variety of disorders, the role of antioxidants against oxidative stress has recently received increased attention. METHODS Twenty male rabbits were served a high-cholesterol (HC, 5 g/kg diet) diet or high-cholesterol diet supplemented with naringin (0.5 g/kg diet) or probucol (0.5 g/kg diet) for 8 weeks to compare the antioxidative effects of the citrus bioflavonoid (naringin) and antioxidative cholesterol-lowering drug (probucol). RESULTS The plasma thiobarbituric acid-reactive substances (TBARS) concentration was not significantly different between the groups, whereas the hepatic TBARS concentration was significantly lower in the probucol group than in both normal and HC control or naringin group. Probucol and naringin supplementation led to an increase in the hepatic superoxide dismutase (SOD) and catalase (CAT) activities, and a decrease in the hepatic mitochondrial hydrogen peroxide (H(2)O(2)) content compared to the HC-control group. However, there was no difference in the cytosolic H(2)O(2) content or cytosolic glutathion peroxidase (GSH-Px) activity in the liver between the groups. Both naringin and probucol supplements significantly increased the plasma vitamin E concentration compared to the HC-control group. As regards the antioxidant enzyme gene expressions, naringin significantly increased the expression of three antioxidant enzyme mRNAs compared to the HC-control group, whereas probucol significantly increased the only SOD mRNA expression. CONCLUSIONS The probucol supplement was very potent in the antioxidative defense system, whereas naringin exhibited a comparable antioxidant capacity based on increasing the gene expressions in the antioxidant enzymes, while also increasing the hepatic SOD and CAT activities, sparing plasma vitamin E, and decreasing the hepatic mitochondrial H(2)O(2) content.

Ursolic acid enhances the cellular immune system and pancreatic β-cell function in streptozotocin-induced diabetic mice fed a high-fat diet

This study investigated the effects of ursolic acid on immunoregulation and pancreatic beta-cell function in type 1 diabetes fed a high-fat diet for 4 weeks. Male mice were divided into non-diabetic, diabetic control, and diabetic-ursolic acid (0.05%, w/w) groups, which were fed a high-fat (37% calories from fat). Diabetes was induced by injection of streptozotocin (200 mg/kg B.W., i.p.). Ursolic acid significantly improved blood glucose levels, glucose intolerance, and insulin sensitivity compared to the diabetic group. The plasma insulin and C-peptide concentrations were significantly higher in the diabetic-ursolic acid group than in the diabetic group. Ursolic acid significantly elevated the insulin levels with preservation of insulin staining of beta-cells in the pancreas. In splenocytes, concanavalin (Con) A-induced T-cell proliferation was significantly higher in the diabetic-ursolic acid group compared to the diabetic group, but liposaccharide (LPS)-induced B-cell proliferation did not differ between groups. Ursolic acid enhanced IL-2 and IFN-gamma production in response to Con A stimulation, whereas it inhibited TNF-alpha production in response to LPS stimulation. In this study, neither streptozotocin nor ursolic acid had effects on lymphocyte subsets. These results indicate that ursolic acid exhibits potential anti-diabetic and immunomodulatory properties by increasing insulin levels with preservation of pancreatic beta-cells and modulating blood glucose levels, T-cell proliferation and cytokines production by lymphocytes in type 1 diabetic mice fed a high-fat diet.