• Journal of Nutrition and Health
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• v.55 no.4
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• pp.462-475
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• 2022

Purpose: Allomyrina dichotoma larvae are one of the approved edible insects with nutritional value and various functional and medicinal properties. Previously we have demonstrated that the Allomyrina dichotoma larval extract (ADLE) ameliorates hepatic insulin resistance in high-fat diet (HFD)-induced diabetic mice through the activation of adenosine monophosphate-activated protein kinase (AMPK). This study investigated the effects of ADLE on insulin resistance in the skeletal muscle and explored mechanisms for enhancing the glucose uptake in palmitate (PAL)-treated C2C12 myotubes. Methods: To induce insulin resistance, the differentiated C2C12 myotubes were treated with PAL (0.5 mM) for 24 hours, and then treated with a 0.5 mg/ml concentration of ADLE, and the resultant effects were measured. The expression levels of glucose transporter-4 (GLUT4), AMPK, and the mitochondrial metabolism-related proteins were analyzed by western blotting. The mRNA expression levels of lipogenesis- related genes were determined by quantitative reverse-transcriptase PCR. Results: The exposure of C2C12 myotubes to 0.5 mg/ml of ADLE increased cell viability significantly compared to PAL-treated cells. ADLE upregulated the protein expression of GLUT4 and enhanced glucose uptake in the PAL-treated cells. ADLE increased the phosphorylated AMPK in both the PAL-treated C2C12 myotubes and HFD-treated skeletal muscle. The reduced expression levels of peroxisome-proliferator-activated receptor gamma co-activator-1 alpha (PGC1α) and uncoupling protein 3 (UCP3) due to the PAL and HFD treatment were reversed by the ADLE treatment. The citrate synthase activity was also significantly increased with the PAL and ADLE co-treatment. Moreover, the mRNA and protein expressions of fatty acid synthesis-related factors were reduced in the PAL and HFD-treated muscle cells, and this effect was significantly attenuated by the ADLE treatment. Conclusion: ADLE activates AMPK, which in turn induces mitochondrial metabolism and reduces fatty acid synthesis in C2C12 myotubes. Therefore, ADLE could be useful for preventing or treating insulin resistance of skeletal muscles in diabetes.

• The Korean Journal of Pharmacology
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• v.32 no.3
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• pp.407-416
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• 1996

The reactive intermediates formed during the metabolism of therapeutic agents, toxicants and carcinogens by cytochromes P450 are frequently capable of covalently binding to tissue macromolecules and causing tissue damage. It has been shown that YH439, a congener of malotilate, is effective in suppressing hepatic P450 2E1 expression. The present study was designed to further establish the mechanistic basis of YH439 protection against toxicant by assessing its effects against chemical-mediated potentiated hepatotoxicity. Retinoyl palmitate (Vit-A) pretreatment of rats for 7 days substantially enhanced carbon tetrachloride hepatotoxicity, as supported by an ${\sim}5-fold$ increase in serum alanine aminotransferase (ALT) activity, as compared to $CCl_4$ treatment alone. The elevation of ALT activity due to Vit-A was completely blocked by the treatment of $GdCl_3$ a selective inhibitor of Kupffer cell activity. Concomitant pretreatment of rats with both YH439 and Vit-A resulted in a 94% decrease in Vit-A-potentiated $CCl_4$ hepatotoxicity. YH439 was also effective against propyl sulfide-potentiated $CCl_4-induced$ hepatotoxicity. Whereas propyl sulfide (50 mg/kg, 7d) enhanced $CCl_4-induced$ hepatotoxicity by >5-fold, relative to $CCl_4$ treatment alone, concomitant treatment of animals with both propyl sulfide and YH439 at the doses of 100 and 200 mg/kg prevented propyl sulfide-potentiated $CCl_4$ hepatotoxicity by 35% and 90%, respectively. Allyl sulfide, a suppressant of hepatic P450 2E1 expression, completely blocked the propyl sulfide-enhanced hepatotoxicity, indicating that propyl sulfide potentiation of $CCl_4$ hepatotoxicity was highly associated with the expression of P450 2E1 and that YH439 blocked the propyl sulfide-enhanced hepatotoxicity through modulation of P450 2E1 levels. Propyl sulfide- and $CCl_4-induced$ stimulation of lipid peroxidation was also suppressed by YH439 in a dose-related manner, as supported by decreases in malonedialdehyde production. The role of P450 2E1 induction in the potentiation of $CCl_4$ toxicity and the effects of YH439 were further evaluated using pyridine as a P450 2E1 inducer. Pyridine pretreatment substantially enhanced the $CCl_4$ hepatotoicity by 23-fold, relative to $CCl_4$ alone. YH439, however, failed to reduce the pyridine-potentiated toxicity, suggesting that the other form(s) of cytochroms P450 inducible by pyridine, but not suppressible by YH439 treatment, may play a role in potentiating $CCl_4-induced$ hepatotoxicity. YH439 was capable of blocking cadmium chloride-induced liver toxicity in mice. These results demonstrated that YH439 efficiently blocks Vit-A-enhanced hepatotoxiciy through Kupffer cell inactivation and that the suppression of P450 2E1 expression by YH439 is highly associated with blocking of propyl sulfide-mediated hepatotoxicity.

• Journal of Animal Science and Technology
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• v.45 no.2
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• pp.199-210
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• 2003

The effect of feeding a cyclic oligosaccharide, $\beta$-cyclodextrin($\beta$CD) on plasma cholesterol and triacylglyceride concentrations and on antithrombotic activity were investigated in rats fed a control chow diet, or one either high in cholesterol or in saturated fat. The bleeding time of $\beta$CD-fed groups was significantly prolonged by 293%, 157% and 218% in normal, high cholesterol and high fat diet fed groups, respectively, as compared to the control group(p<0.05). The whole blood clotting time was significantly increased by 202%, 168% and 211% in normal, high cholesterol and high fat diet fed groups as compared to control group, respectively(p<0.05). The $\beta$CD diet caused a marked decrease in plasma total lipid(TL), triacylglyceride(TAG), total cholesterol (TC) and low density lipoprotein- cholesterol (LDL-C) concentrations. The plasma TL concentration was significantly decreased by 70%, 82% and 87% in normal, high cholesterol and high fat diet fed groups as compared to the control group, respectively(p<0.05). The plasma TAG concentration was significantly decreased by 89%, 43% and 59% in normal, high cholesterol and high fat diet fed groups, respectively, as compared to the control group(p<0.05). The plasma TC concentration was significantly decreased by 28%, 62% and 36% in normal, high cholesterol and high fat diet fed groups, respectively, as compared to the control group(p<0.05). The LDL-C concentration was significantly decreased by 39%, 54% and 25% in normal, high cholesterol and high fat diet fed groups as compared to control group, respectively(p<0.05). The plasma total bile acids contents of $\beta$CD group was significantly increased by 66%, 95% and 97% in normal, high cholesterol and high fat diet fed groups as compared to control group, respectively(p<0.05). The hepatic HMG-CoA reductase activity was significantly lowered by 41% in the $\beta$CD-fed group compared to normal diet fed rats(p<0.05). The fecal steroid excretions of the $\beta$CD groups was significantly increased by 167% in normal diet fed rats(p<0.05). These results suggest that the $\beta$CD has a biological active function on antithrombotic activity and is hypolipidemic, hypotriglyceridemic and hypocholesterolimic agents. These are all effects that can help to prevent obesity and coronary heart disease in humans.

• Journal of Nutrition and Health
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• v.37 no.2
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• pp.88-94
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• 2004

The effects of liquid culture of Coriolus versicolor on weight gain, food intakes, food efficiency ratios, serum and hepatic lipid concentrations, serum protein levels and serum enzyme activities, were studied in growing male rats. Sprague-Dawley rats were given four different types of diets for a succeeding period of 5 weeks, respectively: a normal diet group (7% corn oil), a high fat diet group (7% corn oil＋15% lard), a 20% or 30% C. versicolor diet groups (high fat diet＋20% or 30% C. versicolor in water) according to the levels of C. versicolor supplementation. The body weight gains of the rats fed the 30% C. versicolor diets were lower than those in the rats fed high fat diet. The epididymal fat pad weight of the rats fed high fat diet and 20% or 30% C. versicolor diets were significantly higher than that of the rats fed normal diet. The concentrations of triglyceride in the serum and the liver of the rats fed the 30% C. versicolor diets were more significantly decreased compared to rats on the high fat diet. The concentrations of total cholesterol in the serum and the liver of rats fed the high fat diet, 20% and 30% C. versicolor diets were similar to those of rats fed the normal diet. The HDL-cholesterol concentration and the HDL-cholesterol/total-cholesterol ratio of the rats fed 20% and 30% C. versicolor diets were significantly lower than those of the rats fed high fat diet. But the antherogenic index of the rats fed 20% or 30% C. versicolor diets were significantly higher than those of the rats fed high fat diet. There were no differences in the activities of glutamic oxaloacetic transaminase, glutamic pyruvic transaminase and alkaline phosphatase in the serum among the experimental groups. These results showed that the 30% C. versicolor diet feeding decreased the triglyceride in serum and liver of the rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.9
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• pp.1239-1248
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• 2016

Pumpkin juice (PJ), corn silk tea (CT), and adzuki bean tea (AT) have long been used for treatment of obesity in Korea. This study investigated the efficacy of PJ, CT, AT, and their mixture (PCA) on alteration of body weight and antioxidant metabolism in high-fat diet (HFD)-induced obese rats. After being fed HFD for 4 weeks, SD rats were divided into six groups fed a normal diet (ND), HFD, HFD+PJ [250 mg/kg body weight (BW)], HFD+CT (250 mg/kg BW), HFD+AT (250 mg/kg BW), and HFD+PCA (PJ : CT : AT=1:1:1, 250 mg/kg BW) for another 9 weeks. HFD consumption resulted in total lipid, triglyceride, and total cholesterol accumulation in adipose tissue, which was reduced by administration of PJ, CT, AT, or PCA. The plasma oxygen radical absorbance capacity value and hepatic glutathione peroxidase activity significantly increased compared to the HFD group. The liver thiobarbituric acid reactive substances was significantly lower in the PCA group than the HFD group. HFD-induced DNA damage in hepatocytes, as measured by comet assay, decreased in the PJ, AT, and PCA-supplemented groups. The PCA group exerted a superior antigenotoxic effect compared to other treatments. PCA recovered the concentration of plasma adiponectin, which was reduced by HFD. Adipocyte surface area (%) was significantly higher in the HFD group than the ND group, significantly lower in the PJ and PCA groups than the HFD group, and not significantly different compared with the ND group. Based on the results, supplementation of PJ, CT, AT, and PCA exhibited lipid-lowering effects in adipocytes of HFD-induced obese rats. Furthermore, the PCA group exhibited superior antioxidant activity in all treated groups. This study suggests that a mixed beverage consisting of PJ, CT, and AT may be a significant source of natural antioxidants, which might be helpful in preventing obesity and progress of various oxidative stresses induced by HFD.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.1
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• pp.35-41
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• 2008

The purpose of this study was to investigate the effects of Chungkookjang viscous biopolymer supplementation on blood glucose and serum lipid-lowering in Streptozotocin (STZ)-induced diabetic rats. The rats were divided into three experimental groups; a normal group (N), diabetic control group (D), and a diabetic group with the supplementation of Chungkookjang viscous biopolymer (DCB). The groups were given experimental diets for four weeks. The normal group (C) was fed a casein-based diet, and the Chungkookjang viscous biopolymer group (DCB) received 3% biopolymer added to the casein-based diet. In the diabetic group (D), food intake increased significantly, but weight gain decreased significantly. The food efficiency ratio was significantly lower in the diabetic group. Liver weight increased significantly in the D group as compared to the N group. However, the DCB group showed a significant decrease in liver weight when compared to the D group. Blood glucose decreased significantly in the DCB group after receiving the experimental diet for four weeks, as compared to the diabetic control (p<0.05). Serum triglyceride levels were significantly lower in the DCB group than in the D group, whereas HDL-cholesterol levels were significantly higher (p<0.05). Total cholesterol was decreased in DCB group, but there were no significant differences. Also, LDL-cholesterol level was not significantly different among the experimental groups. Hepatic triglyceride and cholesterol were lower in the DCB group with no significant differences among groups. These results indicate that dietary supplementation of Chungkookjang viscous biopolymer improved glucose lowering and lipid metabolism in diabetic rats.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.3
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• pp.409-415
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• 2011

This study was performed to investigate the effects of Cheonggukjang added with Job's tears (CAJT) on antiobesity and lipid profiles on diet-induced obese rats. Male Sprague-Dawley rats were fed high-fat diet only (A, control), and high-fat diet with Cheonggukjang powder 10% (B), CAJT powder 10% (C), Cheonggukjang powder 20% (D), CAJT powder 20% (E) for 5 weeks. Body weight gains were similar in the experimental groups, but FER was significantly lower in the group E than group A (p<0.05), and adipose tissue weights in groups with Cheonggukjang and CAJT powder were similar to those in the group A. The lengths of small intestine were significantly longer in the groups B, C, D, and E than the group A (p<0.05). Hepatic concentrations of total cholesterol (TC) and triglyceride (TG) were similar to each other. Fecal weights were not significantly different among the groups. Fecal TC concentrations were similar in the experimental groups, but fecal TG concentrations were greatly increased in the groups B, D, and E (p<0.05). The serum TC, HDL-C and LDL-C levels varied slightly among the groups, but serum TG levels were decreased in the group D and E than in the group A (p<0.05). The AI and CRF were marginally decreased in the groups B, D, and E than in the group A (p<0.05). However, blood glucose levels were not significantly different among the groups. From the findings, it had shown that Job's tears Cheonggukjang could improve lipid profiles.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.6
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• pp.1177-1183
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• 2001

This study was done to investigate the effects of ethanol extract of Cassia semen (Cassia tora L.) on the activities of hepatic oxygen free radicals metabolizing enzymes and blood lipid profile in rats of hepatotoxicity induced by ethanol. Sprague-Dawley male rats weighing 100~160 g were divides into 5 groups; control grouts (CON), Cassia semen ethanol extracts (200 mg/kg) treated group (CEL), ethanol (10 mL/kg, 35%) treated group (ETH), Cassia semen ethanol extracts (200 mg/kg) and ethanol treated group (CE1 ) and Cassia semen ethanol extracts (400 mg/kg ) and ethanol treated group (CE2), respectively. Compared with ETH, the growth rate of CE1 and CE2 were to be increased tendency, and in blood levels of total cholesterol, LDL-cholesterol and the activities of alanine aminotranferase and asparate aminotranferase elevated by ethanol were significantly decreased (p<0.05). It was observed that the activities of superoxide dismutase, catalase, xanthine oxidase and glutathione peroxidase of rat liver increased by ethanol, were more decreased by the treatment of Cassia semen ethanol extract than the only ethanol-treated group. The content of glutathione depleted by ethanol treatment was increased in CE1 and CE2. TBA-reactants of liver increased by ethanol were decreased in CE1 and CE2, compared with ethanol-treated group. These results suggested that ethanol extract of Cassia semen may influence upon the ability of oxygen free radical detoxication and lowering of blood lipid level on ethanol-induced hepatotoxicity in rat.

• Journal of Genetic Medicine
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• v.4 no.1
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• pp.72-79
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• 2007

Purpose : Glycogen storage disease type III (GSD-III) is a rare autosomal recessive disorder of glycogen metabolism. The affected enzyme, amylo-1,6-glucosidase, 4-alpha-glucanotransferase (AGL, glycogen debranching enzyme), is responsible for the debranching of the glycogen molecule during catabolism. The disease shows clinical and biochemical heterogeneity, reflecting genotype-phenotype heterogeneity among different patients. In this study, we aim at analyzing mutations of the AGL gene in three unrelated Korean GSD-III patients, and characterizing their clinical and laboratory findings. Methods : We characterized the clinical features of three unrelated Korean GSD-III patients by biochemical, histological and imaging studies. The 35 exons and part of exon-intron boundaries of AGL were analyzed by direct sequencing using genomic DNA extracted from the peripheral leukocytes of patients. Results : Diverse clinical features were observed in these patients including hepatomegaly (all patients), seizures (patient 2), grow th failure (patients 1 and 2), hyperlipidemia (patients 1 and 3), raised transaminase and creatine kinase concentrations (all patients), and mild cardiomyopathy (patient 2). Liver transplantation w as performed in patient 2 due to progressive hepatic fibrosis. A dministration of uncooked corn starch maintained normoglycemia and improved biochemical and growth profiles. DNA sequence analysis revealed mutations in 5 out of 6 alleles. Patient 1 was a compound heterozygote of c.1282 G>A (p.R428K) and c.1306delA (p.S603PfsX6), patient 2 had c.1510_1511insT (p.Y 504L fsX 10), and patient 3 had c.3416 T >C (p.L 1139P) and c.1735+1 G>T (p.Y 538_R578delfsX 4) mutations. A part from the p.R428K mutation, the 4 other substitutions identified w ere nov el. Conclusion : GSD-III patients display variable phenotypic characteristics resembling those of GSD-Ia. Molecular defects in the AGL gene of Korean GSD-III patients are genetically heterogeneous.