• Journal of Physiology & Pathology in Korean Medicine
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• v.30 no.4
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• pp.279-288
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• 2016

To observe the potential hepatoprotective effects of Gongjin-dan on the acute ethanol (EtOH)-induced liver damages in C57BL/6 mice with its possible action mechanisms. EtOH-mediated acute hepatic damages were induced by oral administration of EtOH total 3 doses. The changes on the body weight, liver weight, albumin, TG, AST, ALP, ALT, hepatic TG contents, hepatic antioxidant defense system, TNF-α, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes - SREBP-1c, SCD1, ACC1, FAS, PPARγ and DGAT2 or genes involved in fatty acid oxidation - PPARα, ACO and CPT1 were observed with final liver histopathological inspections after 15 days of continuous administration of silymarin 200 mg/kg, Gongjin-dan (GJD) 400, 200 and 100 mg/kg. The results were compared with silymarin 200 mg/kg treated mice. Marked decreases of body and liver weights, increases of serum AST, ALT, Albumin and TG levels, hepatic TG contents, TNF-α level, CYP 2E1 activity and mRNA expressions of hepatic lipogenic genes or decreases mRNA expressions of genes involved in fatty acid oxidation were observed with histopathological changes related hepatosteatosis increases of immunolabelled hepatocytes, as the results of a binge drinking of EtOH in the present study. Also destroys of hepatic antioxidant defense systems were demonstrated in EtOH control mice as compared with intact vehicle control mice, respectively. The results suggest that oral administration of 400, 200 and 100 mg/kg of GJD favorably protected the liver damages from acute mouse EtOH intoxications.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1349-1353
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• 2012

Increasing evidence has revealed that thy-1 was a potential stem cell marker of liver cancer, but no data have been shown on how thy-1 regulates the pathophysiology of liver cancer, such as proliferation, apoptosis, invasion and migration. We previously demonstrated that thy-1 was expressed in about 1% of hepg2 cells, thy-1+hepg2 cells, but not thy-1-, demonstrating high tumorigenesis on inoculation $0.5{\times}10^5$ cells per BACA/LA mouse after 2 months. In the present study, our results showed that higher expression of thy-1 occurs in 72% (36/50 cases) of neoplastic hepatic tissues as compared to 40% (20/50 cases) of control tissues, and the expression of thy-1 is higher in poorly differentiated liver tumors than in the well-differentiated ones. In addition, thy-1 expression was detected in 85% of blood samples from liver cancer patients, but none in normal subjects or patients with cirrhosis or hepatitis. There was a significant negative correlation between thy-1expression and E-cadherin expression (a marker of invasion and migraton), but not between thy-1 expression and AFP expression in all the liver cancer and blood samples. We further investigated the relationship between thy-1 and E-cadherin in liver cancer hepg2 cell line which was transfected with pReceiver-M29/thy-1 eukaryotic expression vector followed by aspirin treatment. Lower expression of E-cadherin but higher expressions of thy-1 were detected in hepg2 cells transfected with pReceiver-M29/thy-1. Taken together, our study suggested that thy-1 probably regulates liver cancer invasion and migration.

• Natural Product Sciences
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• v.27 no.3
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• pp.201-207
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• 2021

We have previously reported that Acer tegmentosum extract, which is traditionally used in Korea to reduce alcohol-related liver injury, suppresses liver inflammation caused by excessive alcohol consumption and might improve metabolism. The active ingredient, 6-O-galloylsalidroside (GAL), was isolated from A. tegmentosum, and we hypothesized that GAL could provide desirable pharmacological benefits by ameliorating physiological conditions caused by alcohol abuse. Therefore, this study focused on whether GAL could ameliorate alcoholic fat accumulation and repair liver injury in mice. During chronic alcohol consumption plus binge feeding in mice, GAL was administered orally once per day for 11 days. Intrahepatic lipid accumulation was measured in vivo using a noninvasive method, ¹H magnetic resonance imaging, and confirmed by staining with hematoxylin and eosin and Oil Red O. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured using a Konelab system, and the triglyceride content was measured in liver homogenates using an enzymatic peroxide assay. The results suggested that GAL alleviated alcohol-induced steatosis,e as indicated by decreased hepatic and serum triglyceride levels in ethanol-fed mice. GAL treatment also correlated with a decrease in the Cd36 mRNA expression, thus potentially inhibiting the development of alcoholic steatosis via the hepatic de novo lipogenesis pathway. Furthermore, treatment with GAL inhibited the expression of cytochrome P450 2E1 and attenuated hepatocellular damage, as reflected by a reduction in ALT and AST levels. These findings suggest that GAL extracted from A. tegmentosum has the potential to serve as a bioactive agent for the treatment of alcoholic fatty liver and liver damage.

• 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.6
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• pp.1278-1282
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• 2001

Effect of the egg yolks from laying hens intubated, p.o., astaxanthin (designated AEY) on the catabolic response overcome of mice was examined. Female ICR mice (6~7 weeks of age) were adapted in a temperature- and humidity-controlled house for one week and randomly divided into 5 groups (6 mice/cage/treatment). Mice were intubated p.o., AEY (5, 10 and 15 mg), control egg yolk (CEY, 10 mg), or fish oil (5 mg) dissolved in 0.2 mL phosphate buffered saline (PBS) every two days for 14 days. At day 15, the 0.1 mL of lipopolysaccharide solution (LPS, 30$\mu\textrm{g}$/0.1 mL 10 mM HEPES) was injected through tail vein, and then, the body weight of mouse and the amount of feed intake were measured over a period of 72 hours. Control group mice were received only PBS and LPS. AEY treatment suppressed the loss of mice body weight in a dose-response manner. Twenty four hours post LPS injection, the reduced body weight per mouse of AEY 5, AEY 10, and AEY 15 mg treatment groups was 3.70, 3.54, and 3.25 g, respectively. Body weight suppression effect of AEY treatment was greater than that of CEY, but less than fish oil. AEY treatment did not alter thymus weight, but increased the weight of spleen or liver. These results indicate that AEY suppressed the loss of body weight by LPS via any function of the spleen and/or liver.

• Microbiology and Biotechnology Letters
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• v.42 no.1
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• pp.11-17
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• 2014

Selenium is an essential trace element for mammals, but it is very toxic. Therefore, the control of selenium concentrations should be precisely and effectively monitored. Selenium is naturally obtained through foods and seleno-L-methionine (LSeMet) is a major form of selenium. It has been reported that L-SeMet is only converted into Se-adenosyl-L-SeMet. However, a recent study suggested that L-SeMet was directly metabolized into methylselenol ($CH_3SeH$) in mouse liver extract by the reaction of cystathionine ${\gamma}$-lyase (CGL). The canonical reaction of CGL was known to catalyze the cleavage of L-cystathionine to L-cysteine, ${\alpha}$-ketobutyrate and $NH_3$. In the present study, we found that L-SeMet could be directly converted to $CH_3SeH$ using purified homogenous human CGL instead of mouse liver cytosol. Authentic $CH_3SeH$ was prepared by reduction of dimethyldiselenide with sodium tetrahydroborate. The gaseous product of the enzymatic reaction with L-SeMet was analyzed by GC/MS spectrometry. The GC/MS data was identical to that of authentic dinitrophenyl selenoether. We also analyzed the kinetic parameters for the formation of $CH_3SeH$ from L-SeMet by human and mouse CGL. These results suggest that human CGL is a critical enzyme which is responsible for L-SeMet metabolism.

• BMB Reports
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• v.39 no.4
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• pp.346-354
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• 2006

The full-length cDNA of grass carp (Ctenopharyngodon idellus) and silver carp (Hypophthalmichthys molitrix) uncoupling protein 2 (UCP2) was obtained from liver. The grass carp UCP2 cDNA was determined to be 1152 bp in length with an open reading frame that encodes 310 amino acids. Five introns (Intron 3, 4, 5, 6 and 7) in the translated region, and partial sequence of Intron 2 in the untranslated region of grass carp UCP2 gene were also obtained. Gene structure comparison between grass carp and mammalian (human and mouse) UCP2 gene shows that, the UCP2 gene structure of grass carp is much similar to that of human and mouse. Partial UCP2 cDNA sequences of bighead carp (Aristichthys nobilis) and mud carp (Cirrhinus molitorella), were further determined. Together with the common carp (Cyprinus carpio) UCP2 sequence from GenBank (AJ243486), multiple alignment result shows that the nucleotide and amino acid sequences of the UCP2 gene, were highly conserved among the five major Chinese carps that belong to four subfamilies. Using beta-actin as control, the ratio UCP2/beta-actin mRNA (%) was determined to be $149.4{\pm}15.6$ (common carp), $127.4{\pm}22.1$ (mud carp), $96.7{\pm}12.7$ (silver carp), $94.1{\pm}26.8$ (bighead carp) and $63.7{\pm}16.2$ (grass carp). The relative liver UCP2 expression of the five major Chinese carps, shows a close relationship with their food habit: benthos and detrituseating fish (common carp and mud carp) > planktivorious fish (silver carp and bighead carp) > herbivorious fish (grass carp). We suggest that liver UCP2 might be important for Chinese carps to detoxify cyanotoxins and bacteria in debris and plankton food.

• Korean Journal of Food Science and Technology
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• v.31 no.6
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• pp.1661-1666
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• 1999

Yungmijihwgang-Won, Yollyunggobon-Dan and Palmi-Hwan, Korea traditional prescriptions composed of oriental medical herbs, have been used successfully to improve human health and regimen. This study was designed to examine the mechanism of healthful effects of the Korea traditional prescriptions through its antioxidative potentials. Using in vitro antioxidative activity assay system such as DPPH radical quenching assay, superoxide anion radical scavenging assay and inhibition of TBARS production, three Korea traditional prescriptions were observed to have nearly the same antioxidative potentials as ascorbic acid, a well-known strong water-soluble antioxidant. Moreover, we observed reinforced antioxidative effects of these drugs in liver from mouse fed these drugs with 4 weeks. When liver homogenate was incubated with 2.2'-azobis(amidinopropane) dihydrochloride(AAPH), as a free radical initiator, we observed that oxidative damages were decreased and antioxidative potentials were increased in liver homogenate treated these drugs. However, enzymatic antioxidative system as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase was not affected by drug administration.

• Nutrition Research and Practice
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• v.14 no.4
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• pp.299-308
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• 2020

BACKGROUND/OBJECTIVES: Heavy alcohol consumption causes the development of alcoholic liver disease (ALD), a neglected but important public health problem. Many studies have pointed out that probiotics could improve gut health, which is also considered to be a cause of ALD. Therefore, this study screened the probiotics, Lactobacillus casei GKC1 (GKC1), L. fermentum GKF3 (GKF3), Bifidobacterium lactis GKK2 (GKK2), L. rhamnosus GKLC1 (GKLC1), L. paracasei GKS6 (GKS6), and L. plantarum GKM3 (GKM3), for their potential benefits in alleviating ALD for applications to disease prevention. SUBJECTS/METHODS: C57BL/6N mice were divided into 8 groups (n = 6 in each): normal control, positive control (alcohol-diet fed), and treatments of feeding probiotics GKC1, GKF3, GKK2, GKLC1, GKS6, and GKM3 under an oral dose 0.82 g/kg B.W. per day by oral gavage. The experiment was conducted for 8 weeks, and the concentrations of alanine aminotransferase (ALT), aspartate aminotransferase, triglyceride (TG), and total cholesterol (TC) in mice were measured. The glutathione (GSH), catalase (CAT), and histology were analyzed after sacrifice. RESULTS: The results showed a decrease in the serum ALT, liver TG, and liver TC levels in the GKS6, GKM3, and GKLC1 groups compared to the positive control. In addition, the decreasing GSH and CAT levels were inhibited in the GKS6 and GKM3 groups. The histopathological results showed that all probiotics could reduce the accumulation of liver fat. Furthermore, there was a significant difference in GKLC1 with lower stomach damage compared to the alcohol-fed mice without any addition of probiotics. CONCLUSIONS: GKLC1, GKS6, and GKM3 can be used as supplements for alleviating the development of ALD.

• YAKHAK HOEJI
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• v.49 no.4
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• pp.306-311
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• 2005

Semisulospira libertine (SL) has been used as a folk medicine for quenching a thirst, hepatic fever and inflammation in oriental countries. Although SL has been anecdotally ascertained to ameliorate the hepatic diseases, there are no sufficient experimental evidences. The purpose of this study was to examine the effect of Bitam-S, in which SL is a main component, on non-alcoholic fatty liver disease manifested in C57BL/6J ob/ob mice. At 6 week old, the ob/ob mice were randomly divided into four groups; control and three treatment groups. The control mice was to receive a regular diet, and the treatment groups were fed a regular diet with either 250mg/kg, 500mg/kg of Bitam-S (BS250 and BS500) or 300mg/kg of metformin (MT300) for a 8-week period. Bitam-S exerted beneficial effects on lipid homeostasis in ob/ob mice that are not necessarily due to its ability to decrease food intake but its specific effects on hepatic lipogenesis related genes (SREBP1a, FAS and SCD-1). The combined effects of Bitam-S to reduce body weight and lipogenic gene expressions, and reduce the deposition of triglyceride in the liver are indicative of a marked improvement in obesity-related non-alcoholic fatty liver disease. Taken together, Bitam-S has potential as a treatment agent for non-alcoholic fatty liver disease and deserves clinical trial in the near future.