• 대한한방내과학회지
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• 제27권4호
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• pp.811-821
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• 2006

Objectives : Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many methods have been tried to regulate oxygen free radicals for treating diabetes and its complications. Because Mori foliumhas been known to be effective for the treatment of diabetes, the methanol extract of Mori folium was tested for its effectiveness in reducing the oxidative stress induced by streptozotocin. Methods : The crushed Mori folium was extracted 3 times, each time with 3 volumes of methyl alcohol at $60^{\circ}C$ or 24 h. The extract was filtered and evaporated under reduced pressure using a rotary evaporator to yield 11.7 g. Mori folium extract was oral-administered to diabetic rats induced by streptozotocin at 100 mg per 1 kg of body weight for 20 days. The efficacy of the Mori foliumextract was examined with regard to the enzymatic pathways involved in oxygen free radical production and glutathione balance. Results : The effects of the Mori foliumin streptozotocin-induced diabetic rats with regards to body weight, blood glucose and insulin level, hepatic lipid peroxide level, hepatic glutathione level, hepatic glutathione S-transferase and glutathione peroxidase level, hepatic aldose reductase activity, and hepatic sorbitol dehydrogenase activity were shown to be good enough to cure and prevent diabetes and its complications. Conclusions : These results indicated that Mori folium might reduce oxidative stress in tissues and organs by regulating the production of oxygen free radicals. Especially Mori folium might prevent and cure diabetes and its complications by reducing oxidative stress in the ${\beta}-cells$ of the pancreas.

• 한국수의병리학회:학술대회논문집
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• 한국수의병리학회 2002년도 추계학술대회초록집
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• pp.146-146
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• 2002

Hepatic disease has been noted and reported for involvement various detrimental factors. Among many detrimental injury factors, alcohol has been noted for hepatitis, fatty liver, fibrosis, and hepatic cirrhosis. The purpose of this study is to develop animal model for hepatic fibrosis in pig with ethanol, and to search new anti-fibrogenic agent. Twelve male Landrace pigs were divided into 3 groups of 4 animals each. Group 1, 2 and 3 were fed with ceramic water only, ceramic water + liquid diet containing 20％ ethanol and normal tap water + containing 20％ ethanol for 12 weeks, respectively. At week 12, all pigs were immediately sacrificed for collection each tissue and blood. Serologically, serum ALT and AST levels were significantly reversed in group 2, comparing to group 3. They were normal range in pigs of group 1. Microscopically, macrovesicular lipid droplets and moderate necrosis were evident in the tap water + ethanol fed group 3. However, ceramic water intake group 1 showed normal. Moreover, in group 3, little fatty changes and mild necrosis were observed. Collagen fibers were detected in the spaces of surrounding periportal and interlobular areas in the group 3 of tap water + ethanol, but collagen synthesis and its thickness of fibrotic septa connecting portal tracts was markedly reduced in the group 2 of ceramic water + ethanol. In immunohistochemistry, myofibroblasts were detected in the ethanol and tap water treated group 3. No or a few myofibroblasts were observed in groups 1 and 2. CYP 2E1 was rarely detected in group 1 fed ceramic water. However, group 2 showed slightly activation of CYP 2E1 in the area of pericentral, while CYP 2E1 was significantly activated in group 3 fed tap and ethanol. Taken together above, alcohol fibrosis model in pig was established. Furthermore, ceramic water had an inhibitory and protecting ability for alcohol-induced hepatic damages.

• 생약학회지
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• 제40권2호
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• pp.128-136
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• 2009

This study was carried out to investigate the antidiabetic and antioxidative effect of Lycii fructus in the Streptozotocin(STZ)-induced diabetic rats. The effective fractions were prepared as a form of organic solvents of $CH_{3}(CH_{2})_{4}CH_{3}$ $CHCI_{3}$, EtOAc, BuOH and $H_{2}O$ fractions prepared from the EtOH extract of Lycii fructus and The diabetes were induced by an tail-intravenous injection of STZ with a dose of 45 mg/kg dissolved in citrate buffer. The various fractions of Lycii fructus were orally administrated once a day for 7 days. The contents of serum glucose, and triglyceride in the $CHCI_{3}$ fraction and hepatic lipid peroxidation in the EtOAc, BuOH and $H_{2}O$ fractions treated rats were significantly decreased when compared to those of the STZ-control group In addition, an activity of hepatic GST in the BuOH fraction treated rats was significantly increased compared to that of the STZ-control group. whereas, activities of hepatic catalase, GSH-Px in the BuOH fraction treated rats were significantly decreased compared to those of the STZ-control group. Meanwhile, The content of hepatic glycogen and avtivity of hepatic glucokinase in $CHCI_{3}$ fraction treated rats were significantly increased, but activity of glucose-6-pase was significantly decreased in the $CHCI_{3}$ fraction treated rats. In conclusion, these results indicated that the BuOH fraction of Lycii fructus was effective for the antioxidation, and also the $CHCI_{3}$ fraction of Lycii fructus was effective for the antidiabetes in the STZ-induced diabetic rats.

• 한국환경보건학회지
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• 제27권2호
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• pp.10-16
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• 2001

To evaluate an effect of circadian variation on the xylene metabolizing enzyme activities, 50% m-xylene in olive oil(0.25 $m\ell$/100g body weight) was intraperitoneally administered to the rats every other day for 6 days both in the night; 24:00 and the day; 12:00. Then animals were sacrigiced at 8hr after last injection of m-xylene. Hepatic microsomal cytochrome p450 contents were more increased both in control and xylene treated rats of night phase than those of day phase. But the activity of hepatic alcohol dehydrogenase(ADH) in control of night phase showed the similar value with that in those of day phase and xylene treated rats of day phase showed an increasing tendency of hepatic ADH activity as those of night phase showing similar activity. Furthermore, control rats of night phase than those of day phase. And by xylene treatment, enzyme activities of rats of day phase were higher tendency in rats of control but those of night phase were somewhat inhibited. Besides, xylene-treated animals of night phase showed increasing tendency of urinary methylhippuric acid concentration compared with those of day phase. On the other hand, liver weight per body weight(%), hepatic lipid peroxide content and serum xanthine oxidase activity were higher in night phase. And the activities of hepatic oxygen free radical metabolizing enzymes such as xanthine oxidase, gluthathione S-transferase, and xylene-treated rats of night phase than those of day phase. In conclusion, it can be hypothesized on the basis of the results that the accumulation rate of m-xylene intermediate metabolite, i.e. m-methylbenzaldehyde in liver tissus may be higher in night phase than in day phase and it may be responsible for higher liver toxicity in bight phase than in day phase.

• Journal of Nutrition and Health
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• 제35권10호
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• pp.1015-1022
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• 2002

This study was conducted to examine the effects of dietary xylooligosaccharides on hepatic HMG-CoA reductase activity and morphological exchange of liver in rats fed high fat diet. Sprague-Dawley male rats weighing 100 $\pm$ 10 g were randomly divided into four groups, two normal diets and two high fat diets containing 1% cholesterol and 10% lard. Two normal diets were classified into a basal diet (normal group) and 10% xylooligosaccharide diet (NX group). The high fat diet groups were classified into a HF group without xylooligosaccharides diet and HFX group supplemented 10% xylooligosacchride diet. Experimental diets were fed ad libidum to the rats for 4 weeks and then they were sacrificed. The body weight of high fat diet (HF group) was increased more than that of normal group, but it was significantly decreased by xylooligosacchrides supplementation. The food intake was not significantly different among the all groups. The weight of liver, small intestine and cecum of all xylooligosaccharide supplemented groups were significantly heavier than those of normal and HF groups. The activity of hepatic HMG-CoA reductase, a rate limiting enzyme of cholesterol biosynthesis, in xylooligosaccharide supplemented groups was higher than that of HF group. Light micrographs revealed that the structures of hepatocytes in xylooligosaccharide supplemented groups were preserved well, compared to HF group. The xylooligosaccharide supplementation exerted a lipid-lowering action by decreasing cholesterol and triglycerides contents in hepatic tissue. In conclusion, the activity of hepatic HMG-CoA reductase and damage of liver in rats fed high fat diets were improved by dietary xylooligosaccharides.

• Animal Bioscience
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• 제36권2호
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• pp.284-294
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• 2023

Objective: This study investigated the effects of in ovo feeding of γ-aminobutyric acid (GABA) and embryonic thermal manipulation (ETM) on growth performance, organ indices, plasma biochemical parameters, hepatic antioxidant levels, and expression of lipid metabolism-related genes in broilers. Methods: Two hundred and fifty eggs were assigned to one of four treatments: control eggs incubated under standard conditions (CON); eggs that received an in ovo injection of 10% GABA on day 17.5 of incubation (G10); thermally manipulated eggs between days 10 and 18 of incubation at 39.6°C for 6 h daily (TM); and eggs that received both treatments during incubation (G10+TM). After 28 days of rearing, five birds per treatment were selected for blood and organ sampling. Results: No differences were found in hatchability or growth parameters among different treatment groups. Hepatic gene expression of catalase (CAT) and glutathione peroxidase 1 (GPx1) was upregulated (p = 0.046 and p = 0.006, respectively) in the G10+TM group, while that of nuclear factor erythroid 2-related factor 2 (NRF2) was upregulated (p = 0.039) in the G10 group. In addition, the relative gene expression of NADPH oxidase 1 (NOX1) was significantly lower (p = 0.007) in all treatment groups than that in the CON group. Hepatic fatty acid synthase (FAS) levels and average daily feed intake (ADFI) of last week showed a positive correlation (r = 0.50, p = 0.038). In contrast, the relative gene expression of the extracellular fatty acid-binding protein (EXFAB) and peroxisome proliferator-activated receptor-γ (PPAR-γ) were positively correlated (r = 0.48, p = 0.042 and r = 0.50, p = 0.031) with the overall ADFI of birds. Conclusion: Taken together, the results of this study suggest that the combination of in ovo feeding of GABA and ETM can enhance hepatic antioxidant function in broilers.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2021년도 춘계학술대회
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• pp.60-60
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• 2021

Non-alcoholic fatty liver disease (NAFLD), especially including non-alcoholic steatohepatitis (NASH) is one of the common diseases with 25% of prevalence globally, but there is no thera-peutic access available. Amomum villosum var. xanthioides (Wall. ex Baker) T.L.Wu & S.J.Chen (AX), which is a medicinal herb and traditionally used for treating digestive tract disorders in Asia countries. We aimed to examine pharmacological effects of ethyl acetate fraction of AX (AXEF) against ER stress-induced NASH mice model using C57/BL6J male mice by tunicamycin (TM, 2 mg/kg) injection focusing on the oxidative stress. Mice were orally administrated AXEF (12.5, 25, or 50 mg/kg), silymarin (50 mg/kg) or distilled water daily for 5 days, and outcomes for fatty liver, inflammation, and oxidative stress were measured in serum or liver tissue levels. AXEF drastically attenuated hepatic ER stress-induced NASH which were evidenced by decreases of li-pid droplet accumulations, serum liver enzymes, hepatic inflammations, and cell death signals in the hepatic tissue or serum levels. Interestingly, AXEF showed potent antioxidant effects by quenching of reactive oxidative stress and its final product of lipid peroxide in the hepatic tissue, specifically increase of metallothionein (MT). To confirm underlying actions of AXEF, we ob-served that AXEF increase MT1gene promoter activities in the physiological levels. Collectively, AXEF showed antioxidant properties on TM-induced ER stress of NASH by enhancement of MTs.

• Journal of Yeungnam Medical Science
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• 제41권2호
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• pp.103-112
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• 2024

Background: Nonalcoholic fatty liver disease (NAFLD) is characterized by an increase in hepatic triglyceride content and increased inflammatory macrophage infiltration through the C-C motif chemokine receptor (CCR) 5 pathway in the liver. DA-6034 (7-carboxymethyloxy-3',4',5-trimethoxy flavone), is a synthetic derivative of eupatilin that exhibits anti-inflammatory activity in inflammatory bowel disease. However, the effect of DA-6034 on the inflammatory response in NAFLD is not well elucidated. Therefore, we aimed to determine the effect of DA-6034 on hepatic steatosis and inflammation. Methods: Forty male C57BL/6J mice were divided into the following four groups: (1) regular diet (RD), (2) RD with DA-6034, (3) high fat diet (HFD), and (4) HFD with DA-6034. All mice were sacrificed 12 weeks after the start of the experiment. The effects of DA-6034 on macrophages were assessed using RAW 264.7 cells. Results: DA-6034 not only reduced hepatic triglyceride levels and lipid accumulation but also macrophage infiltration and proinflammatory cytokines in HFD-fed mice. According to fluorescence-activated cell sorter analysis, DA-6034 reduced the CD8⁺ T cell fraction in the liver of HFD-fed mice. DA-6034 also reduced CCR5 expression and the migration of liver macrophages in HFD-fed mice and inhibited CCR2 ligand and CCR4 ligand, which stimulated the migration of macrophages. Conclusion: Overall, DA-6034 attenuates hepatic steatosis and inflammation in obesity by regulating CCR5 expression in macrophages.

• BMB Reports
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• 제42권9호
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• pp.568-573
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• 2009

Fatty acid oxidation (FAO) defects cause abnormal lipid accumulation in various tissues, which provides an opportunity to uncover novel genes that are involved in lipid metabolism. During a gene expression study in the riboflavin deficient induced FAO disorder in the chicken, we discovered the dramatic increase in mRNA levels of an uncharacterized gene, ANKRD9. No functions have been ascribed to ANKRD9 and its orthologs, although their sequences are well conserved among vertebrates. To provide insight into the function of ANKRD9, the expression of ANKRD9 mRNA in lipidperturbed paradigms was examined. The hepatic mRNA level of ANKRD9 was repressed by thyroid hormone ($T_3$) and fasting, elevated by re-feeding upon fasting. However, ANKRD9 mRNA level is reduced in response to apoptosis. Transient transfection assay with green fluorescent protein tagged- ANKRD9 showed that this protein is localized within the cytoplasm. These findings point to the possibility that ANKRD9 is involved in intracellular lipid accumulation.

• Asian-Australasian Journal of Animal Sciences
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• 제24권9호
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• pp.1274-1281
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• 2011

Dietary protein restriction affects lipid metabolism in rats. This study was performed to determine the effect of a low protein diet on hepatic lipid metabolism and insulin sensitivity in growing male rats. Growing rats were fed either a control 20% protein diet or an 8% low protein diet. Feeding a low protein diet for four weeks from 8 weeks of age induced a fatty liver. Expression of acetyl-CoA carboxylase, a key lipogenic enzyme, was increased in rats fed a low protein diet. Feeding a low protein diet decreased very low density lipoprotein (VLDL) secretion without statistical significance. Feeding a low protein diet down-regulated protein expression of microsomal triglyceride transfer protein, an important enzyme of VLDL secretion. Feeding a low protein diet increased serum adiponectin levels. We performed glucose tolerance test (GTT) and insulin tolerance test (ITT). Both GTT and ITT were increased in protein-restricted growing rats. Our results demonstrate that dietary protein restriction increases insulin sensitivity and that this could be due to low-protein diet-mediated metabolic adaptation. In addition, increased adiponectin levels may influences insulin sensitivity. In conclusion, dietary protein restriction induces a fatty liver. Both increased lipogenesis and decreased VLDL secretion has contributed to this metabolic changes. In addition, insulin resistance was not associated with fatty liver induced by protein restriction.