• 대한한방내과학회지
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• 제33권4호
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• pp.438-447
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• 2012

Objectives : In this study, we investigated the effect and the underlying mechanism of ethanol extract of Benincasa seeds on a cellular model of non-alcoholic fatty liver disease (NAFLD) established by treating HepG2 cells with palmitate. Methods : We evaluated ethanol extract of Benincasa seeds (EEBS) for its hepatic lipid-lowering potential in fatty acid overloaded HepG2 cells. After incubation in palmitate containing media with or without EEBS, intracellular neutral lipid accumulations were quantified by Nile red staining. We also investigated the effect of EEBS on lipogenesis and ${\beta}$-oxidation. $LXR{\alpha}$-dependent SREBP-1c activation, expression of lipogenic genes, and expression of ${\beta}$-oxidation related genes were determined with or without pretreatment of EEBS. Results : EEBS significantly attenuated palmitate-induced intracellular neutral lipid accumulation in HepG2 cells. EEBS suppressed fatty acid synthesis by inhibiting $LXR{\alpha}$-dependent SREBP-1c activation. EEBS also repressed SREBP-1c mediated induction of lipogenic genes, including ACC, FAS, and SCD-1. However, EEBS had no effect on ${\beta}$-oxidation related CPT-1 and $PPAR{\alpha}$ gene expression. Conclusions : Our results suggest that EEBS has an efficacy to decrease hepatic lipid accumulation, and this effect was mediated by inhibiting the $LXR{\alpha}$-SREBP-1c pathway that leads to expression of lipogenic genes and hepatic steatosis. Therefore, the Benincasa seeds may have a potential clinical application for treatment of this chronic liver disease.

• 대한한의학방제학회지
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• 제28권2호
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• pp.189-198
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• 2020

Objectives : This study investigated the liver-protective effects of MJY2018, a Herbal formula, against alcoholic fatty liver disease and anti-oxidative effects. Methods : Its effects were investigated in an alcoholic fatty liver disease model in male C57BL/6 mice, which were fed Lieber-DeCarli liquid diet containing ethanol. MJY2018 (100 and 200 mg/kg bw/day) or silymarin (50 mg/kg bw/day) were orally administered daily in the alcoholic fatty liver disease mice for 16 days. Results : The results indicate that MJY2018 promotes hepatoprotection by significantly reducing aspartate transaminase (AST) and alanine transaminase (ALT) levels as indicators of liver damage in the serum. Furthermore, MJY2018 reduced accumulation of triglyceride and total cholesterol, increased levels of superoxide dismutase (SOD) and glutathione (GSH) in the livers of the alcoholic fatty liver disease mice model. Additionally, it improved the serum alcohol dehydrogenase (ADH) activity. Conclusions : These results indicate that MJY2018 were effective in improving and protecting oxidative stress and alcoholic liver disease.

• Nutrition Research and Practice
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• 제3권2호
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• pp.95-101
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• 2009

It has been reported that dietary polyunsaturated fats (PUFA) increase liver injury in response to ethanol feeding. We tested the hypothesis that diets rich in linoleic acid (18:2n-6) would affect acute liver injury after acetaminophen injection and that protein restriction might exacerbate the liver injury. We examined effects of feeding diets with either 15% (wt/wt) corn oil or 14% beef tallow and 1% corn oil for six weeks with either 6 or 20 g/100 g protein on acute hepatotoxicity. After the feeding period, liver injury was induced by injecting either with 600 mg/kg body weight acetaminophen suspended in gum arabic-based vehicle, or with vehicle alone during fasting status. Samples of liver and plasma were taken for analyses of hepatic glutathione (GSH) levels and liver-specific enzymes [(Glutamate-pyruvate transaminase (GPT) and glutamate-oxaloacetate transaminase (GOT)], respectively. Whereas GSH level was significantly lower in only group fed 15% corn oil with 6 g/100 g protein among acetaminophen-treated groups, activities of GPT and GOT were significantly elevated in all groups except the one fed beef tallow with 20 g/100 g protein, suggesting low protein might exacerbate drug-induced hepatotoxicity. The feeding regimens changed the ratio of 18:2n-6 to oleic acid (18:1n-9) in total liver lipids approximately five-fold, and produced modest changes in arachidonic acid (20:4n-6). We conclude that diets with high 18:2n-6 promote acetaminophen-induced liver injury compared to diets with more saturated fatty acids (SFA). In addition, protein restriction appeared to exacerbate the liver injury.

• 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.

• 대한본초학회지
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• 제33권6호
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• pp.61-70
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• 2018

Objectives : Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of hepatic triglycerides (TG) that leads to inflammation and fibrosis. Crataegi Fructus ethanol extract (CE) is a korean traditional herb that used for digestive diseases. It has been investigated that CE has the effect that prevent hepatotoxicity caused by CCl4 or GaIN and regulate the inflammatory in several organs. However, a hypolipidemic effect of CF has not been reported. Methods : The purpose of this study is that examine the lipid accumulation inhibitory effect of CE on NAFLD. We checked the body and liver weight change of MCD-diet induced mice with/without administration of CE. The blood lipid levels of C57BL/6J mice were checked by biochemistry. Also we observed the liver histology of MCD-diet induced mice and investigate the molecular mechanisms in MCD-diet-induced NAFLD in C57BL/6J mice. Results : CE improved MCD-diet-induced lipid accumulation and TG and TC levels. Also, CE decreased hepatic lipogenesis such as SREBP-1, $C/EBP{\alpha}$, $PPAR{\gamma}$, ACC and FAS. Besides, we also found out that CE increased AMPK phosphorylation. These results indicated that CE has the same ability to activate AMPK and then reduce SREBP-1, and FAS expression, finally leading to inhibit hepatic lipogenesis and hepatic antioxidative ability. Conclusions : In this report, we found CE exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in MCD-diet induced NAFLD model. Therefore, CE extract may be active in the prevention of fatty liver.

• 대한의생명과학회지
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• 제16권1호
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• pp.33-38
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• 2010

Culinary herbs and spices have received much attention since they contain high concentrations of bioactive ingredients for antioxidant and anti-inflammatory activities. Protection effect of the herb and spice against acute alcohol consumption has been investigated using zebrafish as a vertebrate model. During 30 days bathed in water containing 1% Et-OH and the designated herb or spice, the survival rate of the Et-OH group was decreased sharply (up to 20% at 10 days). The cinnamon-fed group showed the highest and longer survival rate up to 80% up to for 30 days under the presence of Et-OH, while clove-fed group showed 40% survival rate for 25 days. Et-OH group serum exhibited the weakest antioxidant ability from ferric ion removal ability (FRA) assay; FRA ability was increased in the cinnamon-fed group up to 414%, while the clove and laurel group increased 256% and 309%, respectively. Histologic observation and Oil-red O staining showed hepatic tissue damage was severe in the Et-OH group. The cinnamon- or clove-fed group showed much ameliorated hepatic tissue morphology with minimized steatosis. The cinnamon- or clove-fed group showed lower serum GOT and GPT levels than the Et-OH group. Among hepatic tissue extract, the clove-fed group exhibited the lowest level of GOT and GPT. These results suggest that consumption of cinnamon and clove might be beneficial to attenuate progress of acute fatty liver change by alcohol consumption.

• Natural Product Sciences
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• 제27권3호
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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.

• 대한한방내과학회지
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• 제35권2호
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• pp.175-183
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• 2014

Objectives : We tried to uncover the anti-lipogenic effect and underlying mechanism of Laminaria japonica on an experimental cellular model of non-alcoholic fatty liver disease. Methods : Ethanol extract of Laminaria japonica (LJ) was prepared. Intracellular lipid content of palmitate-treated HepG2 cells was evaluated with or without LJ treatment. We measured the effects of LJ on liver X receptor ${\alpha}$ ($LXR{\alpha}$) and sterol regulatory element-binding transcription factor-1c (SREBP-1c) expression, transcription level of lipogenic genes, including acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and nuclear factor erythroid 2-related factor 2 (Nrf2) activation in HepG2 cells. Results : LJ markedly attenuated palmitate-induced intracellular lipid accumulation in HepG2 cells. LJ suppressed $LXR{\alpha}$-dependent SREBP-1c activation, and SREBP-1c mediated induction of ACC, FAS, and SCD-1. Furthermore, LJ activated Nrf2, which plays an important cytoprotective role in non-alcoholic fatty liver disease. Conclusions : Our study suggests that LJ has the potential to alleviate hepatic lipid accumulation, and this effect was mediated by inhibiting the $LXR{\alpha}$-SREBP-1c pathway that leads to hepatic steatosis. In addition, the anti-lipogenic potential may, at least in part, be associated with activation of Nrf2.

• 생약학회지
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• 제43권1호
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• pp.72-78
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• 2012

Alnus japonica Steud (A. japonica) have long been used in the traditional medicine for gastric disorder, hepatitis and fatty liver in Korea. Antiulcer effects of A. japonica hot water extract (AJ ext) were evaluated by in vitro antibacterial activity against H. pylori, by the inhibitory action against the in vitro gastric $H^+/K^+$-ATPase and using rat models of gastric mucosal damage and gastric ulcer induced by HCl-ethanol, indomethacin, and restraint and water-immersion stress. For the determination of antibacterial activity of AJ ext against H. pylori, the activity of urease which released from H. pylori was measured in culture. AJ ext showed weak antibacterial activity against H. pylori with the growth inhibitions of 37% and 61% by adding final concentrations of 500 and $1000{\mu}g/ml$ culture, respectively at 24 h. To observe the inhibitory activity of AJ ext against the $H^+/K^+$-ATPase in hog gastric membrane vesicle, $IC_{50}$ value of AJ ext was $806.3{\mu}g/ml$. Pretreatment of AJ ext (200, 500 mg/kg, p.o.) prevented in a dose-dependent manner the acute gastritis in HCl-ethanol model and the formation of gastric ulcer in indomethacin model and restraint and water-immersion stress model. These results suggest that the AJ ext can be used for prevention and treatment of gastric mucosal damage and ulcers induced by various stress.

• 대한한의학회지
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• 제38권2호
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• pp.53-60
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• 2017

Objectives: Beakdugu-tang (BDGT) consists of three medicinal herbs, and this prescription has long been used in treatment of various digestant problem in Korea. In this study, we designed to clarify mechanisms by which Korean traditional digestive medicine, BDGT, may exert anti-hepatic steatosis effects via improved insulin resistance cell model in human hepatocellular carcinoma (HepG2) and monocyte (THP-1). Materials and methods: The preparation of BDGT and constituents were extracted with 70% ethanol. HepG2 and THP-1 were treated with different concentrations of BDGT and constituents in the presence and absence of stimulants such as free fatty acids (FFAs) and oxidized low-density lipoprotein (ox-LDL), respectively. Results: The BDGT and its constituents inhibited the FFAs-stimulated lipid accumulation in HepG2 cells. Ethanol extracts of Amomum cardamomum (ACE) improved the ox-LDL induced insulin resistance in THP-1 cells. Also, treatment of monocytic cells with ACE increased anti-hepatic steatosis related gene levels including ABCA, ABCG and SR-B1. Conclusion: The results suggest that the ethanol extract of BDGT and its constituents potently inhibit the FFAs- and ox-LDL induced liver steatosis via improved insulin resistance.