• Korean Journal of Veterinary Research
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• v.51 no.2
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• pp.159-164
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• 2011

Alcohol abuse and its medical and social consequences are a major health problem in many areas of the world. Korean red ginseng (KRG) has been traditionally used for the treatment of liver disease. This study was conducted to evaluate the hepatoprotective effects of KRG against hepatotoxicity in Sprague- Dawley rats treated with ethanol (EtOH). Administration of EtOH for 20 days induced significant changes in serum biochemical parameters (aspartate aminotransferase, alanine transaminase, and glucose) accompanied by histological changes in the liver tissue. Treatment with KRG prior to administration of EtOH inhibited the EtOH-induced biochemical and histological changes of the liver. In perfused rat livers, administration of EtOH caused an increase in lactate dehydrogenase (LDH) release into the perfusate and activated the pro-apoptotic Bax protein but inhibited the anti-apoptotic Bcl-2 protein. Pretreatment with KRG prior to administration of EtOH decreased the EtOH-induced LDH release and inhibition of Bcl-2 protein. These results suggest that KRG exerts anti-apoptotic effects and alleviated EtOH-induced liver injury in rats.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.5-5
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• 2021

Alcoholic and nonalcoholic steaohepatitis is a leading form of chronic liver disease with few biomakers ad treatment options currently available. a progressive disease of NAFLD may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, we extracted HIMH0021, which is an active flavonoid component in the Acer tegmentosum extract, has been shown to protect against liver damage caused by hepatic dysfunction. Therefore, in this study, we aimed to investigate whether HIMH0021 could regulate steatohepatitis and liver fibrosis during alcoholic or nonalcoholic metabolic process. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.

• Food Science of Animal Resources
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• v.37 no.6
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• pp.931-939
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• 2017

Alcoholic liver disease (ALD) is a complex multifaceted disease that involves oxidative stress and inflammation as the key mediators. Despite decades of intensive research, there are no FDA-approved therapies, and/or no effective cure is yet available. Probiotics have received increasing attention in the past few years due to their well-documented gastrointestinal health-promoting effects. Interestingly, emerging studies have suggested that certain probiotics may offer benefits beyond the gut. Lactobacillus fermentum LA12 has been previously demonstrated to play a role in inflammatory-related disease. However, the possible protective effect of L. fermentum LA12 on ALD still remain to be explored. Thus, the aim of this study was to evaluate the possible protective effect of L. fermentum LA12 on alcohol-induced gut barrier dysfunction and liver damage in a rat model of alcoholic steatohepatitis (ASH). Daily oral administration of L. fermentum LA12 in rat model of ASH for four weeks was shown to significantly reduced intestinal nitric oxide production and hyperpermeability. Moreover, small intestinal histological- and qRT-PCR analysis further revealed that L. fermentum LA12 treatment was capable of up-regulating the mRNA expression levels of tight junction proteins, thereby stimulating the restitution of barrier structure and function. Serum and hepatic analyses also revealed that the restoration of epithelial barrier function may prevent the leakage of endotoxin into the blood, subsequently improve liver function and hepatic steatosis in the L. fermentum LA12-treated rats. Altogether, results in this study suggest that L. fermentum LA12 may be used as a dietary adjunct for the prevention and treatment of ASH.

• Biomolecules & Therapeutics
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• v.21 no.4
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• pp.264-269
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• 2013

Silymarin has been introduced fairly recently as a hepatoprotective agent. But its mechanisms of action still have not been well established. The aim of this study was to make alcoholic fatty liver model of rats in a short time and investigate silymarin's protective effects and possible mechanisms on alcoholic fatty liver for rats. The model of rat's alcoholic fatty liver was induced by intragastric infusion of ethanol and high-fat diet for six weeks. Histopathological changes were assessed by hematoxylin and eosin staining (HE). The activities of alanine transarninase (ALT) and aspartate aminotransferase (AST), the levels of total bilirubin (TBIL), total cholesterol (TC) and triglyceride (TG) in serum were detected with routine laboratory methods using an autoanalyzer. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and the level of malondialdehyde (MDA) in liver homogenates were measured by spectrophotometry. The TG content in liver tissue was determined by spectrophotometry. The expression of nuclear factor-${\kappa}B$ (NF-${\kappa}B$), intercellular adhesion molecule-1 (ICAM-1) and interleukin-6 (IL-6) in the liver were analyzed by immunohistochemistry. Silymarin effectively protected liver from alcohol-induced injury as evidenced by improving histological damage situation, reducing ALT and AST activities and TBIL level in serum, increasing SOD and GPx activities and decreasing MDA content in liver homogenates and reducing TG content in liver tissue. Additionally, silymarin markedly downregulated the expression of NF-${\kappa}B$ p65, ICAM-1 and IL-6 in liver tissue. In conclusion, Silymarin could protect against the liver injury caused by ethanol administration. The effect may be related to alleviating lipid peroxidation and inhibiting the expression of NF-${\kappa}B$.

• The Journal of Internal Korean Medicine
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• v.32 no.4
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• pp.550-564
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• 2011

Objectives : Oxidative stress seems to play a major role in mechanisms by which ethanol causes liver injury. Previous studies have shown that treatment with Yinjinchunggan-tang (Yinchenqinggan-tang, YJCGT) has protective effects on alcoholic liver disease. The aim of this study was to investigate the protective effects of YJCGT on alcohol-induced oxidative stress. Materials and Methods : In vitro, we evaluated the inhibitory activities of YJCHT on DPPH(1,1-diphenyl-2-picryl-hydrazyl), xanthine oxidase, trypsin, and hyaluronidase. In a cell culture model, we measured cell viability and proliferation, and the activities of superoxide dismutase (SOD), and catalase (CAT) after YJCGT treatment in C34 and E47 cell lines, and HepG2 cells transfected with/ without cytochrome P450IIE1 (CYP2E1) gene. In vivo, we estimated serum level of hepatic biochemical markers, and alcohol concentration in the blood. Results : YJCGT showed significant free radical scavenging activity against DPPH and xanthine oxidase and decreased hyaluronidase activity effectively in vitro. YJCGT also increased cell viability, and proliferation in C34 and in E47 cell lines, and increased activities of superoxide dismutase, and catalase in C34 and in E47 cell lines. YJCGT reduced serum AST, LDH, and total cholesterol level in some of the results, and reduced blood alcohol concentration in vivo, as well. Conclusions : This study suggests that YJCGT has protective effects on oxidative stress by inhibiting alcohol-induced suppression of antioxidant enzyme activities.

• The Korea Journal of Herbology
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• v.38 no.1
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• pp.31-43
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• 2023

Objective : Alcoholic liver disease (ALD) is caused by excess alcohol intake. In the liver, alcohol breakdown results formation of toxic byproducts that lead to damage to tissue. This study is to investigate the therapeutic effects of Paeoniae Radix Alba and Puerariae Radix combination (PP) on ALD. Methods : PP was analyzed for polyphenolic compounds and free radical scavenging activity. ALD mouse model was induced by feeding ethanol and water (Control), silymarin (50 mg/kg), low-dose (PP: 100 mg/kg) or high-dose (PP: 200 mg/kg) was orally administrated to ALD mice for 14 days. The serum was assessed with levels of AST, ALT, total bilirubin, total cholesterol, and triglyceride. Liver tissues were evaluated for ROS levels, degree of liver damage and protein expression. Results : The 3:1 (Paeoniae Radix Alba:Puerariae Radix) ratio showed the best antioxidant values for the experiment. In ALD model, levels of AST, ALT, total bilirubin, total cholesterol, and triglyceride were significantly increased in the Control and the levels were decreased by treatment of PP. In addition, increased ROS, ONOO^- and MDA levels in the Control were reduced in the PP groups. Western blot analysis figured out that proteins related to ROS and cholesterol metabolism were higher in ALD than in PP-treated ALD. Antioxidant enzyme expression was low in the control group and increased by PP treatment. Conclusion : Our results suggest that PP has the potential to be a medicine in ALD in terms of regulating oxidative stress and adjusting lipid metabolism.

• Journal of Nutrition and Health
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• v.49 no.6
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• pp.420-428
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• 2016

Purpose: In this study, we investigated the effects of Cirsium setidens ethanolic extract (CS) on the development of alcoholic fatty liver and associated injury. Methods: Sprague-Dawley male rats were fed either Lieber-DeCarli control (C) or ethanol (35.5% of total calories) liquid diet with 0 (E), 100 mg/kgBW CS (E+LCS), or 500 mg/kgBW CS (E+HCS) for 8 weeks. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as TG and cholesterol concentrations in the serum and liver tissues were measured by colorimetric assays. Liver histopathology was examined by Hematoxylin-eosin staining of the fixed liver tissues. Protein levels of phosphorylated-AMP activated protein kinase (p-AMPK), phosphorylated-acetyl CoA carboxylase (p-ACC), phosphorylated-nuclear factor kappa B (p-$NF{\kappa}B$), and $TNF{\alpha}$ were measured by Western blot analyses. Results: Both doses of CS markedly suppressed alcohol-induced lipid droplets accumulation in the liver tissues and significantly inhibited alcohol-induced increases in activities of serum ALT and serum AST. Similarly, CS significantly reduced hepatic and serum TG concentrations. Compared to groups fed alcohol only, CS supplementation strongly increased hepatic levels of p-AMPK and p-ACC. Further, CS significantly inhibited alcohol-induced phosphorylation of $NF{\kappa}B$, which was associated with reduced hepatic protein levels of $TNF{\alpha}$. Conclusion: Our data demonstrated that CS has a protective effect against alcoholic liver injury, which was associated with activation of AMPK and inhibition of $NF{\kappa}B$.

• Biomedical Science Letters
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• v.9 no.1
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• pp.21-27
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• 2003

Hepatic subcellular $\alpha$-D-mannosidases activities and its Km and Vmax values were determined in chronic ethanol intoxicated rats with extrahepatic cholestasis induced by common bile duct ligation to manifest the biochemical background of alcohol drinking hazard under the hepatobiliary disease. In case of extrahepatic cholestasis, chronic ethanol intoxication in animals led to the increased activities of liver Golgi and microsomal $\alpha$-D-mannosidase as well as the Vmax values of these enzymes. However, the difference of Km values on hepatic subcellular enzymes were not found between the experimental groups. Therefore, the results indicate that the liver Golgi and microsomal $\alpha$-D-mannosidase may be more induced in chronic ethanol intoxication animals in case of cholestasis. Accordingly, the resulting data supported the fact that alcoholic drinks may led to enhancement of the hepatobiliary liver damage.

• Korean Journal of Agricultural Science
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• v.51 no.2
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• pp.169-178
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• 2024

Cordyceps militaris L. (C. militaris) has been traditionally used as tonic medicine for metabolic syndrome. Cordycepin, has been reported with immunomodulatory, antitumor, and hepatoprotective effect, is the main extract from C. militaris. This study was conducted to evaluate the alcohol degradation and hepatoprotective effect of cordycepin-enriched C. militaris extract (CM) powder in chronic and binge ethanol (ethanol Lieber-DeCarli diet)-fed male C57BL/6 Mice. Cordycepin-enriched C. militaris extract powder was orally administered once daily at dose levels of 0, 125, 250, and 500 mg·kg^-1·day^-1 for 16 days. For evaluating alcohol degradation, ethanol concentration and alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activity were measured in serum. Serum ethanol (EtOH) concentration was decreased at CM treated groups, and the activities of ADH and ALDH were increased dose-dependently at CM treated groups compare to EtOH model group. In clinical chemistry, the values of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were lower in CM treated groups than those in EtOH model group. Additionally, absolute and relative (to body weight) liver weights were statistically decreased in the CM treated groups compared to the EtOH model group. In conclusion, our study showed that cordycepin-enriched C. militaris extract powder exhibits hepatoprotective effect by upregulating the ADH and ALDH enzyme in an alcoholic liver disease model.

• Korean Journal of Veterinary Service
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• v.26 no.4
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• pp.345-359
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• 2003

A number of toxicants have been incriminated as a causing hepatic disease. Among many detrimental injury, alcohol has been noted for hepatitis, fatty liver, fibrosis, and hepatic cirrhosis. The purpose of this study was to develop animal model for hepatic fibrosis in pigs fed ethanol, and to search for a new anti-fibrogenic agent via this model. Twelve male Landrace pigs were divided into 3 groups of 4 animals each. Group 1, 2 and 3 were fed with active ceramic water only, ceramic water + liquid diet containing 15% ethanol and normal tap water + liquid diet containing 15% 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, as compared to group 3. They were normal range in pigs of group 1. Microscopically, macrovesicular lipid droplets and moderate hepatocellular necrosis were evident in the tap water + ethanol fed group 3. However, the active ceramic water treated group 1 showed normal architecture. Moreover, in group 2, mild fatty changes and necrosis were observed in hepatocytes. Collagen fibers were increased in spaces surrounding periportal and interlobular connective tissues in the group 3 of tap water + ethanol, but collagen synthesis and its thickness of fibrotic septa connecting portal tracts were markedly reduced in the group 2 of ceramic water + ethanol. Myofibroblasts were detected mainly in the interlobular connective tissues of pig liver of group 3 treated ethanol and tap water. Few to no myofibroblasts were observed in groups 1 and 2. CYP2E1 was not or rarely detected in group 1 fed ceramic water. However, group 2 showed slightly activation of CYP2E1 in the area of pericentral vein, while CYP2E1 was significantly activated in group 3 fed tap water and ethanol. Based on the above data, we believe that we have developed a unique alcohol induced fibrosis model in pig, which will be useful in developing anti-fibrotic agents and drugs. Furthermore, the active ceramic water used in our study had an inhibitory and may be protective against ethanol induced hepatic toxicity and fibrosis.