• The Journal of Internal Korean Medicine
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• v.37 no.3
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• pp.442-452
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• 2016

Objectives: This study was performed to investigate the anti-lipogenic effect and the mechanism of Jungmanbunso-hwan extract (JMBSH) on a cellular model of non-alcoholic fatty liver disease (NAFLD) caused by palmitate in HepG2 cells.Methods: The JMBSH was prepared, andHepG2 cells were treated with various concentrations of JMBSH in order to perform an MTT assay. The HepG2 cells were cultivated in palmitate-containing media with or without extract of JMBSH. The intracellular lipid content in the HepG2 cells was examined. The effects of JMBSH on sterol regulatory element-binding transcription factor-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD-1), and AMP-activated protein kinase (AMPK) activation in HepG2 cells were measured.Results: JMBSH did not reduce HepG2 cell viability under 1,000 μg/mL. JMBSH considerably decreased intracellular lipid accumulation caused by palmitate in HepG2 cells. JMBSH repressed expression of SREBP-1c, which mediates the induction of lipogenic genes (ACC, FAS, and SCD-1). JMBSH also activated AMPK, which plays animportant role in the regulation of hepatic lipid metabolism.Conclusions: This study suggested that JMBSH relieves hepatic steatosis by repressing SREBP-1c, which mediates the induction of lipogenic genes. The anti-lipogenic effect of JMBSH may also be related to the activation of AMPK. Therefore, JMBSH could potentially be applied to NAFLD treatment after further clinical studies.

• The Journal of Internal Korean Medicine
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• v.40 no.1
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• pp.38-57
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• 2019

Objective: This study reviewed recent clinical research trends regarding the effects of herbal medicine treatment containing diuretic herbs on nonalcoholic fatty liver disease (NAFLD) in China. Methods: We reviewed clinical studies on NAFLD from the China Academic Journal of the China National Knowledge Infrastructure from January 1, 2016, to September 10, 2018. Results: Thirty-nine papers from 86 studies were reviewed. The most commonly used herbal prescriptions included Alismatis Rhizoma(澤瀉), Salviae miltiorrhizae Radix (丹蔘), Crataegii Fructus (山査), Polia Sclerotium (茯?), Bupleuri Radix (柴胡), and Cassiae Semen (決明子). The treatment effective rate, liver function test, serum lipid test, radiological examination, and symptom comparisons were used to analyze the treatments. In 32 of the papers, the effective treatment rate was 76.9%-100%, and the effectiveness in the experimental group was significantly higher than that in the control group (p<0.05). The risk ratio for the treatment effective rate was 1.26. The mean difference of ALT was -13.44 U/L (95% confidential interval, -24.45 U/L, -2.44 U/L, p=0.0166). Conclusion: Herbal medicine containing diuretic herbs has been demonstrated to be an effective and useful treatment for NAFLD. Clinical studies that are more scientific and systematic should be actively conducted in the future, and the results of the current study could be used as basic data in future clinical studies on herbal medicine treatment for NAFLD.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.10
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• pp.1576-1584
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• 2013

This study is carried out to assess the relative effects of different doses of dietary glucose or fructose on non-alcoholic fatty liver disease (NAFLD) and hepatic metaflammation in a rodent model of type 2 diabetes. KK/HlJ male mice were fed experimental diets as follows: 1) control (CON), 2) moderate glucose (MG, 30% of total calories as glucose), 3) high glucose (HG, 60% of total calories as glucose), 4) moderate fructose (MF, 30% of total calories as fructose), and 5) high fructose (HF, 60% of total calories as fructose) for three weeks. Food intake was not affected by treatments. Compared with HF, HG not only increased serum fasting glucose and area under the curve during oral glucose tolerance test, but also decreased the levels of serum insulin and adiponectin. It indicated that glucose control was complicated via high glucose intake. High fructose treatment led to increased triglyceride in the serum and liver. In comparison to HG, high fructose diet activated NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome consisting of apoptosis-associated speck-like protein containing a CARD (ASC), NLRP3 and caspase 1, which increases interleukin (IL)-$1{\beta}$ maturation and secretion. The activation of NLRP3 inflammasome was accompanied by increased levels of tumor necrosis factor alpha (TNF-${\alpha}$) and IL-6. However, the expression of NLRP3 inflammasome components and pro-inflammatory cytokines did not differ between CON and HG. These data suggested that dietary fructose triggers hepatic metaflammation accompanied by NLRP3 inflammasome activation and has deleterious effects on NAFLD.

• The Korea Journal of Herbology
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• v.37 no.5
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• pp.17-26
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• 2022

Objective : The aim of the present study is to examine hepatic lipid-lowering and anti-inflammatory effects of silymarin combined with Jakyakgamcho-tang on non-alcoholic fatty liver disease in a high fat diet-induced obese mice model. Methods : C57BL/6 mice were divided into four dietary groups: (1) Normal, (2) Control (60% high-fat diet), (3) Control + silymarin 50 mg/kg/day (Silymarin), (4) Control + Silymarin 50 mg/kg/day + Jakyakgamcho-tang 100 mg/kg/day (SPG). After 12 weeks administration, mice were sacrificed and lipids and inflammation-related biomarkers were analyzed liver and plasma. Results : Silymarin and SPG treatments significantly lowered body and liver weights compared to the Control. Serumlipids (triglyceride (TG), total cholesterol) and pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin 1𝛽, and IL-6) concentrations were significantly lowered in the Silymarin and SPG groups than the Control group. Silymarin and SPG treatments suppressed hepatic TG level and hepatic lipid droplets compared to the Control. Theses two treatments significantly increased hepatic kinase B1 and AMP-activated protein kinase protein levels, and significantly decreased hepatic key lipogenic enzymes (acetyl-CoA carboxylase, fatty acid synthase and stearyl coenzyme A desaturase 1) protein levels than the Control. SPG also significantly increased hepatic fatty acid oxidation-related protein (peroxisome proliferator-activated receptor alpha and uncoupling protein 2) levels than the Control. Conclusions: Silymarin and SPG suppressed hepatic lipid accumulation by regulating hepatic protein expression, and lowered blood pro-inflammatory cytokines concentrations though the synergic effect of silymarin and Jakyakgamchotang was not clear.

• Toxicological Research
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• v.24 no.2
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• pp.129-135
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• 2008

The results of recent studies indicate that high levels of free fatty acids(FFAs) and adipokines may be the main causes of non-alcoholic liver disease; however, the molecular mechanism that links FFAs to lipotoxicity remains unclear. In the present study, we treated HepG2 cells with FFA(either palmitate or oleate) to investigate the mechanisms involved in lipotoxicity in the liver cells. We also treated cells with palmitate in the presence of a chemical chaperone, 4-phenylbutyric acid(PBA), to confirm the involvement of ER stress in lipotoxicity. Palmitate significantly induced cytotoxicity in dose- and time-dependent manners. Apoptosis was also significantly induced by palmitate as measured by caspase-3 activity and DAPI staining. Palmitate led to increased expressions of the spliced form of X-box-protein(Xbp)-1 mRNA and C/EBP homologous transcription factor(CHOP) protein, suggesting activation of the unfolded-protein response. PBA co-incubation significantly attenuated apoptosis induced by palmitate. The above data demonstrate that high levels of palmitate induce apoptosis via the mediation of ER stress in the liver cells and that chemical chaperones act to modulate ER stress and accompanying apoptosis.

• Annual Conference of KIPS
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• 2017.04a
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• pp.982-983
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• 2017

본 연구는 최근 문제가 되고 있는 비알콜성 간 질환에 대한 빅 데이터의 사전 데이터를 만들기 위해 마우스에서 고지방 식이와 Streptozotocin ((STZ)로 모델을 제작하였고, 당뇨와 비만 정도를 측정하여 질환발생 정도를 확인하였다. 또한, MR영상의 지속적인 촬용으로 질환발생과정에 대해 3D분석 소프트웨어로 평가되었다.

• Clinical Endoscopy
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• v.57 no.3
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• pp.309-316
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• 2024

The treatment of obesity and its comorbidities ranges from clinical management involving lifestyle changes and medications to bariatric and metabolic surgery. Various endoscopic bariatric and metabolic therapies recently emerged to address an important therapeutic gap by offering a less invasive alternative to surgery that is more effective than conservative therapies. This article comprehensively reviews the technical aspects, mechanism of action, outcomes, and future perspectives of one of the most promising endoscopic bariatric and metabolic therapies, named duodenojejunal bypass liner. The duodenojejunal bypass liner mimics the mechanism of Roux-en-Y gastric bypass by preventing food contact with the duodenum and proximal jejunum, thereby initiating a series of hormonal changes that lead to delayed gastric emptying and malabsorptive effects. These physiological changes result in significant weight loss and improved metabolic control, leading to better glycemic levels, preventing dyslipidemia and non-alcoholic fatty liver disease, and mitigating cardiovascular risk. However, concern exists regarding the safety profile of this device due to the reported high rates of severe adverse events, particularly liver abscesses. Ongoing technical changes aiming to reduce adverse events are being evaluated in clinical trials and may provide more reliable data to support its routine use in clinical practice.

• Biomolecules & Therapeutics
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• v.32 no.2
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• pp.214-223
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• 2024

Metabolic abnormalities in the liver are closely associated with diverse metabolic diseases such as non-alcoholic fatty liver disease, type 2 diabetes, and obesity. The aim of this study was to evaluate the ameliorating effect of robinetin (RBN) on the significant pathogenic features of metabolic failure in the liver and to identify the underlying molecular mechanism. RBN significantly decreased triglyceride (TG) accumulation by downregulating lipogenesis-related transcription factors in AML-12 murine hepatocyte cell line. In addition, mice fed with Western diet (WD) containing 0.025% or 0.05% RBN showed reduced liver mass and lipid droplet size, as well as improved plasma insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. CD38 was identified as a target of RBN using the BioAssay database, and its expression was increased in OPA-treated AML-12 cells and liver tissues of WD-fed mice. Furthermore, RBN elicited these effects through its anti-histone acetyltransferase (HAT) activity. Computational simulation revealed that RBN can dock into the HAT domain pocket of p300, a histone acetyltransferase, which leads to the abrogation of its catalytic activity. Additionally, knock-down of p300 using siRNA reduced CD38 expression. The chromatin immunoprecipitation (ChIP) assay showed that p300 occupancy on the promoter region of CD38 was significantly decreased, and H3K9 acetylation levels were diminished in lipid-accumulated AML-12 cells treated with RBN. RBN improves the pathogenic features of metabolic failure by suppressing the p300-CD38 axis through its anti-HAT activity, which suggests that RBN can be used as a new phytoceutical candidate for preventing or improving this condition.

• Journal of Digital Convergence
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• v.17 no.8
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• pp.283-291
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• 2019

The aim of investigated the role of FABP5 in the hepatic lipogenesis and lipid metabolisms. Mice were overexpressed and silenced liver FABP5 using virus particles. Mice were fed a Western-type diet or regular chow for 1week and then sacrificed mouse after 24hr fasted. Liver homogenates were used for protein analysis by Western blot and mRNA levels by RT-PCR. Hepatic and serum lipids were analysed by thin-layer chromatography. Mice fed a Western-type or high saturated fat diet revealed large increases in FABP5 expression. However, FABP5 mRNA levels were drastically reduced under fasted. Hepatic TG was significantly increased FABP5-OEAV mice, but a significantly decreased hepatic free cholesterol under fed. The discovered a substantial decrease in hepatic TG mass with FABP5 silencing. In these data, presented evidence for an important role of FABP5 in hepatic lipogenesis and hepatic TG storage. FABP5 may also be a potential target in the treatment of NAFLD, metabolic syndrome, and obesity. Furthermore, studies to which transcription factors are involved in FABP5 expression and regulation.

• Natural Product Sciences
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• v.17 no.4
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• pp.285-290
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• 2011

The rhizome of Alisma orientale Juzep (Alismataceae) has been used as a crude drug for diabetes, edema, inflammation and urinary disturbances in oriental medicine. Recent animal studies have shown that the extract of Alisma orientale rhizome (AOR) can potently lower high levels of serum lipids and improve insulin resistance, which are usually detected in patients and animals with non-alcoholic fatty liver disease. So, we studied the antioxidative effects of AOR extracts and fraction in vitro and their protective effects against acute hepatotoxicity induced by $CCl_4$ in vivo.. We then investigated the effects of each fraction on hepatotoxicity induced by tert-butyl hydroperoxide (t-BHP). DAOR (dichloromethane fraction of the Alisma orientale rhizome) scavenged free radicals and superoxide anions. DAOR protected against $CCl_4$ induced hepatotoxicity. DAOR had hepatoprotective and antioxidative effects against t-BHP-induced hepatotoxicity in HepG2 cells and in rats.