• YAKHAK HOEJI
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• v.42 no.6
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• pp.589-597
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• 1998

Effects of Mori Folium Ethanol Soluble Fraction (MFESF) on mRNA expression of glucose transporters, acetyl-CoA carboxylase (ACC) and leptin were examined in db/db mice. 500 and 1000mg/kg dose for MFESF (designated by SY 500 and SY 1000, respectively) and 5mg/kg dose for acarbose were administered for 6 weeks. Quantitations of glucose transporters (GLUT-2 and GLUT-4), ACC and leptin mRNA were performed by RT-PCR and in vitro transcription with co-amplification of rat ${\beta}$-actin gene as an internal standard. Muscular GLUT-4 mRNA expression in MFESF-treated groups were increased dose dependently. On the other hand, MFESF caused the GLLT-4 and leptin mRNA expressions in adipose tissue to decrease dose dependently, which means that triglyceride synthesis in adipocytes might be decreased and consequently signals adipocytes to inhibit the synthesis and release of leptin. Hepatic ACC mRNA expression in MFESF-treated groups was also decreased. and this may result in lowering of serum triiglyceride level. In contrast, liver GLUT-2 mRNA expressions in MFESF-treated and acarbose groups were increased. Higher rate of glucose uptake into hepatocytes is known to inhibit a phosphoenolpyruvate carboxykinase (PEPCK)-catalyzed reaction, which is a rate-limiting step in gluconeogenesis.

• Nutrition Research and Practice
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• v.12 no.2
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• pp.110-117
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• 2018

BACKGROUND/OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is closely associated with metabolic syndrome. In the present study, we observed the effect of ethanol extract of Allium fistulosum (EAF) on NAFLD and have suggested the possibility of using EAF as a natural product for application in the development of a treatment for NAFLD. MATERIALS/METHODS: The preventive effect on hepatic lipid accumulation was estimated by using an oleic acid (OA)-induced NAFLD model in vitro and a Western diet (high-fat high-sucrose; WD)-induced obese mouse model. Animals were divided into three groups (n = 7): normal diet group (ND), WD group, and WD plus 1% EAF group. RESULTS: EAF reduced OA-stimulated lipid accumulation in HepG2 cells in the absence of cellular cytotoxicity and significantly blocked transcriptional activation of sterol regulatory element-binding protein 1 and fatty acid synthase genes. Subsequently, we investigated these effects in vivo in mice fed either ND or WD in the presence or absence of EAF supplementation. In comparison to the ND controls, the WD-fed mice exhibited increases in body weight, liver weight, epididymal fat weight, and accumulation of fat in hepatocytes, and these effects were significantly attenuated by EAF supplementation. CONCLUSIONS: Allium fistulosum attenuates the development of NAFLD, and EAF elicits anti-lipogenic activity in liver. Therefore, EAF represents a promising candidate for use in the development of novel therapeutic drugs or drug combinations for the prevention and treatment of NAFLD.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.489-496
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• 1995

Artemisia messes-schmidiana var viridis(Compositae) has been used for jaundice, hepatitis, diuretic and liver cirrhosis etc. 1-naphthylisothiocyanate(ANIT) has been used as a model compound to study mechanisms of intrahepatic cholestasis in laboratory animals as rat and mouse. The purposes of present study are to examine pharmacological effects of Artemisia messes-schmidiana var viridis water extract(AMWE) on alterations of triacylglycerol, cholesterol, protein, albumin and A/G ratio levels in serum, of histopathological appearances of liver, and that of hepatic microsomal cytochrome P-450 contents. Increased serum triacylglycerol levels by ANIT were significantly decreased with AMWE. However, AMWE posttreatment aggravated ANIT-induced cholesterol increase. Serum total protein and albumin contents, and A/G ratio were decreased in all ANIT-treated groups, and there were increased compared with control by AMWE posttreatment. Hepatic microsomal cytochrome P-450 contents were decreased in either AMWE and ANIT treatment, which greatly increased with AMWE pretreatment. On the other hand, in histological findings, our results shown that ANIT induced increase of lipid droplets and widening of sinusoidal capillary and these phenomena were disappeared with AMWE treatment. In conclusion, AMWE have choleresis effect. Also, AMWE improved lipid metabolism, protection and regeneration of hepatocytes in ANIT-induced cholestasis.

• Korean Journal of Veterinary Research
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• v.35 no.3
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• pp.481-488
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• 1995

In oriental folk medicine, Artemisia messes-schmidiana var viridis(Compositae) has been used for jaundice, hepatitis, diuretic and liver cirrhosis etc. 1-naphthylisothiocyanate(ANIT) has been used for more than 20 years as a model compound to study mechanisms of intrahepatic cholestasis in laboratory animals as rat and mouse. Various biochemical and morphological changes including biliary epithelial and parenchymal cell necrosis occur in the liver of animals treated with ANIT. The purposes of present study are to examine pharmacological effects of Artemisia messes-schmidiana var viridis water extract(AMWE) on alterations of secretion volume and total bile acids level in bile juice, and that of serum AST, ALT, ALP, bilirubin, and glucose levels in rat. AMWE stimulated bile secretion and recovered ANIT-induced cholestasis. Bile acid concentrations increased to more than 60% compared with normal by ANIT, which were returned toward normal value with AMWE treatment. Serum AST and ALT activities were increased by ANIT and yet which were significantly decreased with AMWE treatment. In addition, this effect was apparent in AMWE pretreatment group. Serum glucose levels were increased with AMWE and ANIT, while were decreased compared with control in AMWE posttreatment group. Increased serum total bilirubin contents and ALP activities by ANIT were significantly decreased with AMWE posttreatment. In conclusion, AMWE exerted bile acid-independent choleresis effect and then improved to normal conditions ANIT-induced cholestatic syndromes. Also, AMWE have protective and regenerative effect of hepatocytes in rat.

• Journal of Ginseng Research
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• v.43 no.2
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• pp.179-185
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• 2019

Background: Oxidative stress induces the production of reactive oxygen species (ROS), which play important causative roles in various pathological conditions. Black ginseng (BG), a type of steam-processed ginseng, has drawn significant attention due to its biological activity, and is more potent than white ginseng (WG) or red ginseng (RG). Methods: We evaluated the protective effects of BG extract (BGE) against oxidative stress-induced cellular damage, in comparison with WG extract (WGE) and RG extract (RGE) in a cell culture model. Ethanolic extracts of WG, RG, and BG were used to evaluate ginsenoside profiles, total polyphenols, flavonoid contents, and antioxidant activity. Using AML-12 cells treated with $H_2O_2$, the protective effects of WGE, RGE, and BGE on cellular redox status, DNA, protein, lipid damage, and apoptosis levels were investigated. Results: BGE exhibited significantly enhanced antioxidant potential, as well as total flavonoid and polyphenol contents. ATP levels were significantly higher in BGE-treated cells than in control; ROS generation and glutathione disulfide levels were lower but glutathione (GSH) and NADPH levels were higher in BGE-treated cells than in other groups. Pretreatment with BGE inhibited apoptosis and therefore protected cells from oxidative stress-induced cellular damage, probably through ROS scavenging. Conclusion: Collectively, our results demonstrate that BGE protects AML-12 cells from oxidative stress-induced cellular damages more effectively than WGE or RGE, through ROS scavenging, maintenance of redox status, and activation of the antioxidant defense system.

• The Korea Journal of Herbology
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• v.36 no.1
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• pp.1-8
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• 2021

Objective : Citri Unshius Pericarpium (Citrus unshiu peel) has been used in Korean medicine to treat indigestion, vomiting, coughing and phlegm. This study investigated the hepatoprotective effect of ethanol extract of Citrus unshiu peel (CEE) in cadmium (CdCl2)-treated mouse model. Methods : CEE was dissolved in water and administered orally to mice once a day for 7 consecutive days. The mice were then exposed to a single intraperitoneal (i.p.) injection of cadmium (4 mg/kg body weight) to induce acute hepatotoxicity. At the end of the experiment, blood and liver tissue samples were collected, analyzed for alanine aminotransferase (ALT), aspartate aminotransferase (AST), and histopathological evaluation. Liver damage was assessed as the percentage of degenerative areas of the hepatic parenchyma, the number of degenerative hepatocytes, and the number of infiltrated inflammatory cells. Results : In cadmium-treated rats, pretreatment with CEE significantly reduced the serum ALT and AST levels associated with liver damage. Histopathologically, CEE prevented degenerative changes on the hepatic tissues including confluent necrosis, congestions and infiltration of inflammatory cells. CEE also reduced the elevation of oxidative stress markers (nitrotyrosine and 4-hydroxynonenal) and apoptosis markers (cleaved caspase-3 and cleaved PARP) positive cells. PARP protein expression in liver tissue was also restored by CEE. Conclusion : This study showed that CEE exerted antioxidant and anti-apoptotic effects against cadmium-induced liver injury. Thus, it can be concluded that CEE can be used to prevent liver damage caused by cadmium.

• BMB Reports
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• v.55 no.8
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• pp.401-406
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• 2022

Ahnak, a large protein first identified as an inhibitor of TGF-β signaling in human neuroblastoma, was recently shown to promote TGF-β in some cancers. The TGF-β signaling pathway regulates cell growth, various biological functions, and cancer growth and metastasis. In this study, we used Ahnak knockout (KO) mice that underwent a 70% partial hepatectomy (PH) to investigate the function of Ahnak in TGF-β signaling during liver regeneration. At the indicated time points after PH, we analyzed the mRNA and protein expression of the TGF -β/Smad signaling pathway and cell cycle-related factors, evaluated the cell cycle through proliferating cell nuclear antigen (PCNA) immunostaining, analyzed the mitotic index by hematoxylin and eosin staining. We also measured the ratio of liver tissue weight to body weight. Activation of TGF-β signaling was confirmed by analyzing the levels of phospho-Smad 2 and 3 in the liver at the indicated time points after PH and was lower in Ahnak KO mice than in WT mice. The expression levels of cyclin B1, D1, and E1; proteins in the Rb/E2F transcriptional pathway, which regulates the cell cycle; and the numbers of PCNA-positive cells were increased in Ahnak KO mice and showed tendencies opposite that of TGF-β expression. During postoperative regeneration, the liver weight to body weight ratio tended to increase faster in Ahnak KO mice. However, 7 days after PH, both groups of mice showed similar rates of regeneration, following which their active regeneration stopped. Analysis of hepatocytes undergoing mitosis showed that there were more mitotic cells in Ahnak KO mice, consistent with the weight ratio. Our findings suggest that Ahnak enhances TGF-β signaling during postoperative liver regeneration, resulting in cell cycle disruption; this highlights a novel role of Ahnak in liver regeneration. These results provide new insight into liver regeneration and potential treatment targets for liver diseases that require surgical treatment.

• Journal of Marine Bioscience and Biotechnology
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• v.14 no.2
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• pp.61-68
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• 2022

This study aimed to investigate the hepatoprotective activities of the sea cucumber products, including extracts and hydrolysates, in vitro and in vivo. Dried sea cucumber, produced on the western coast of Korea, was boiled in water or 70% ethanol at 85℃ or 100℃ for 18 or 24 h, respectively, to extract bioactive compounds. The enzymatic hydrolysates were prepared by reacting the dried sea cucumber with pepsin or neutral protease (PNL) under optimal enzyme conditions. The anti-inflammatory effect of the samples was investigated using RAW 264.7 cells treated with lipopolysaccharide (LPS). The amount of nitric oxide (NO) was produced from the cells treated with LPS and each sample was compared. Therefore, the pepsin hydrolysate treatment decreased NO production compared to LPS sole treatment. Furthermore, the effects of the samples on cell injury in the hepatic cell line and bisphenolA-induced hepatic injury mouse model were investigated. The water extracts and the pepsin hydrolysates of sea cucumber significantly inhibited cell injury generated in the hepatocytes without cytotoxicity (p < 0.05), whereas the ethanol extracts were cytotoxic. However, these results indicate that the extracts and the enzymatic hydrolysates derived from sea cucumber can be used as beneficial materials for inhibiting liver damage.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.40-47
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• 2023

Activation of the NLRP3 inflammasome is a necessary process to induce fibrosis in nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH) is a kind of NAFLD that encompasses the spectrum of liver disease. It is characterized by inflammation and ballooning of hepatocytes during steatosis. We tested whether inhibiting the NLRP3 inflammasome could prevent the development and pathology of NASH. We identified loganin as an inhibitor of the NLRP3 inflammasome and investigated whether in vivo administration of loganin prevented NASH symptoms using a methionine-choline deficient (MCD) diet model in mice. We found that loganin inhibited the NLRP3 inflammasome activation triggered by ATP or nigericin, as shown by suppression of the production of interleukin (IL)-1β and caspase-1 (p10) in mouse primary macrophages. The speck formation of apoptosisassociated speck-like protein containing a caspase recruitment domain (ASC) was blocked by loganin, showing that the assembly of the NLRP3 inflammasome complex was impaired by loganin. Administration of loganin reduced the clinical signs of NASH in mice fed the MCD diet, including hepatic inflammation, fat accumulation, and fibrosis. In addition, loganin reduced the expression of NLRP3 inflammasome components in the liver. Our findings indicate that loganin alleviates the inflammatory symptoms associated with NASH, presumably by inhibiting NLRP3 inflammasome activation. In summary, these findings imply that loganin may be a novel nutritional and therapeutic treatment for NASH-related inflammation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.2
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• pp.318-323
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• 2004

This study has been carried out to investigate the effect of the beverage contained Radix puerariae (15%) and Bambusae caules in Liquamen Phyllostachyos (1%) on the alcohol administered mouse. The control group was treated with alcohol (40% alcohol, 8.0 mL/kg of body weight), experimental group 1 (Exp.1) was administered with beverage (8.0 mL/kg of body weight) before alcohol treatment, and experimental group 2 (Exp.2) was administered with beverage after alcohol treatment. Blood alcohol concentrations were decreased by 11% (in Exp. 1) and 17% (in Exp. 2) compared with control group. The concentrations of serum aspartate aminotransferase (AST) were slightly increased in Exp. 1 and Exp.2, but alanine aminotransferase (ALT) levels were not changed compared with control group. Mn-Superoxide dismutase activity was increased by about 70% in the experimental groups in comparison to control group. The Exp. 1 and Exp. 2 contained more periodic-acid Schiff (PAS)-positive materials than the control group. Electron microscopical observations showed that, cell organelles of hepatocytes were more disoriented in the control group than in Exp. 1 and Exp. 2. These results suggest that the beverage contained Radix puerariae and Bambusae caules in Liquamen Fhyllostachyos is a safe and effective therapeutic agent for alcohol abuse.