• The Journal of Korean Medicine
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• v.32 no.3
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• pp.44-49
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• 2011

Objective: This study aimed to get information on the current status of therapies to date for non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH). Methods: All randomized clinical controlled trial (RCT)-derived papers for NAFLD or NASH were reviewed via PubMed Database. Results: 39 RCTs met the review criteria, of which 15 and 24 papers were for NAFLD and NASH, respectively. 83% of the papers were released since 2006, and 30 studies were conducted for western medicines, antioxidants and lifestyle intervention whereas nine trials were done using herbal medicine or acupuncture which showed positive outcome. Conclusions: NAFLD and NASH are new epidemic disorders which can be a target of traditional Oriental medicine. This study will be helpful for the Oriental medicine-based strategies or therapeutic development for them.

• The Journal of Korean Medicine
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• v.32 no.3
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• pp.50-54
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• 2011

Objective: To understand the characteristic of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH), and study the traditional Korean medicine (TKM)-based strategies or therapeutics for them. Methods: A male patient with NASH was treated with only Oriental therapies, and then the clinical outcome was evaluated by serum biochemical parameters and radiographs. Result: The clinical and biochemical values of the patient fluctuated over three years according to the treatments and cessation of herbal medicines. Conclusion: NASH or NAFLD are now prevalent and these disorders could be targets of TKM, and this case report would provide useful information.

• 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.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2021.04a
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• pp.60-60
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• 2021

Non-alcoholic fatty liver disease (NAFLD), especially including non-alcoholic steatohepatitis (NASH) is one of the common diseases with 25% of prevalence globally, but there is no thera-peutic access available. Amomum villosum var. xanthioides (Wall. ex Baker) T.L.Wu & S.J.Chen (AX), which is a medicinal herb and traditionally used for treating digestive tract disorders in Asia countries. We aimed to examine pharmacological effects of ethyl acetate fraction of AX (AXEF) against ER stress-induced NASH mice model using C57/BL6J male mice by tunicamycin (TM, 2 mg/kg) injection focusing on the oxidative stress. Mice were orally administrated AXEF (12.5, 25, or 50 mg/kg), silymarin (50 mg/kg) or distilled water daily for 5 days, and outcomes for fatty liver, inflammation, and oxidative stress were measured in serum or liver tissue levels. AXEF drastically attenuated hepatic ER stress-induced NASH which were evidenced by decreases of li-pid droplet accumulations, serum liver enzymes, hepatic inflammations, and cell death signals in the hepatic tissue or serum levels. Interestingly, AXEF showed potent antioxidant effects by quenching of reactive oxidative stress and its final product of lipid peroxide in the hepatic tissue, specifically increase of metallothionein (MT). To confirm underlying actions of AXEF, we ob-served that AXEF increase MT1gene promoter activities in the physiological levels. Collectively, AXEF showed antioxidant properties on TM-induced ER stress of NASH by enhancement of MTs.

• Journal of Yeungnam Medical Science
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• v.29 no.2
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• pp.73-76
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• 2012

More and more children are becoming obese and overweight due to several factors that include a high energy density in the diet (a high fat intake) and low energy expenditure. Consequently childhood obesity is becoming a significant health problem. Fat tissue releases many cytokines such as resistin, tumor necrosis factor-${\alpha}$, leptin, interleukin-6. These adipocytokines induce obesity-related insulin resistance. Insulin resistance is a key component of obesity-related metabolic problems such as hypertension, type 2 diabetes mellitus, dyslipidemia, non-alcoholic steatohepatitis, acanthosis nigricans and polycystic ovarian syndrome. This review article focused on insulin resistance and its related metabolic diseases.

• 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.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.10 no.2
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• pp.179-184
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• 2007

Purpose: Obesity has recently emerged as a significant health problem in the pediatric population, and the prevalence of non-alcoholic fatty liver disease is increasing in tandem with a significant rise in childhood obesity. Therefore, this study was conducted to clarify the risk factors of non-alcoholic steatohepatitis in obese children. Methods: We enrolled 84 obese children who visited the pediatric obesity clinic at Yeung-Nam university hospital. The patients were divided into two groups based on their alanine aminotransferase (ALT) level (separated at 40 IU/L), and the mean of ages, total cholesterol levels, HDL-cholesterol levels, LDL-cholesterol levels, triglyceride (TG) levels, as well as the mean obesity index, and body fat percentage of the two groups were then compared. Results: When the mean of ages ($10.5{\pm}1.6$ vs. $10.7{\pm}2.0$ years), total cholesterol levels ($183.0{\pm}29.1$ vs. $183.7{\pm}31.3$ mg/dL), HDL-cholesterol levels ($53.0{\pm}10.2$ vs. $55.7{\pm}13.0$ mg/dL), LDL-cholesterol levels ($113.4{\pm}30.2$ vs. $113.0{\pm}30.0$ mg/dL), triglyceride levels ($99.4{\pm}62.9$ vs. $114.2{\pm}47.3$ mg/dL), obesity indexes ($44.7{\pm}12.2$ vs. $47.9{\pm}15.1%$), and body fat percentages ($32.7{\pm}5.0$ vs. $34.0{\pm}4.8%$) of group 1 (ALT${\leq}$40 IU/L) were compared with those of group 2 (ALT${\geq}$41 IU/L), no significant differences were observed (p>0.05). However, hypertriglyceridemia (TG${\geq}$110 mg/dL) was more frequent in group 2 than in group 1 (p=0.023). Conclusion: TG may be an important risk factor in non-alcoholic steatohepatitis and further study regarding the risk factors in non-alcoholic steatohepatitis is required.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.4
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• pp.299-310
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• 2023

Non-alcoholic fatty liver disease (NAFLD) is a complex disorder characterized by the accumulation of fat in the liver in the absence of excessive alcohol consumption. It is one of the most common liver diseases worldwide, affecting approximately 25% of the global population. It is closely associated with obesity, type 2 diabetes, and metabolic syndrome. Moreover, NAFLD can progress to non-alcoholic steatohepatitis, which can cause liver cirrhosis, liver failure, and hepatocellular carcinoma. Currently, there are no approved drugs for the treatment of NAFLD. Therefore, the development of effective drugs is essential for NAFLD treatment. In this article, we discuss the experimental models and novel therapeutic targets for NAFLD. Additionally, we propose new strategies for the development of drugs for NAFLD.

• BMB Reports
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• v.47 no.8
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• pp.457-462
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• 2014

The pathogenesis of non-alcoholic steatohepatitis (NASH) is not fully understood. In the present study, both in vitro and in vivo vimentin expression and secretion in NASH were investigated. The exposure of palmitate and lipopolysaccharide (LPS) to HepG2 cells enhanced caspase-3 activity and vimentin expression, respectively. The combined effects of both treatments on vimentin expression and caspase-3 activation appeared to be synergic. In contrast, blockade of caspase-3 activity by zVADfmk resulted in a significant reduction of cleaved vimentin and secreted vimentin into the culture supernatant. Similarly, lipid accumulation and inflammation occurred in mice fed a methionine-choline-deficient diet; thus, vimentin expression and serum cleaved vimentin levels were increased. However, vimentin was not significantly upregulated, and no cleavage occurred in mice fed a high-fat diet. It was conclusively determined that lipid accumulation in hepatocytes induces apoptosis through a caspase-3 dependent pathway; whereas, LPS stimulates vimentin expression, leading to its cleavage and secretion. Increased vimentin fragment levels indicated the existence of substantial hepatocellular death via an apoptotic mechanism.

• IMMUNE NETWORK
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• v.10 no.6
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• pp.181-187
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• 2010

Excessive alcohol consumption is one of the critical causative factors leading to alcoholic liver disease (ALD). ALD is characterized by a wide spectrum of liver damage, ranging from simple uncomplicated liver steatosis (fatty liver) to steatohepatitis and liver fibrosis/cirrhosis. It has been believed that the obvious underlying cause for ALD is due to hepatocyte death induced by alcohol itself. However, recent sparkling studies have shown that diverse immune responses contribute to ALD because liver is enriched with numerous immune cells. Especially, a line of evidence has suggested that innate immune cells such as Kupffer cells and natural killer (NK)/NKT cells are significantly involved in the pathogenesis of ALD via production of pro-inflammatory cytokines and other mediators. Indeed, more interestingly, hepatic stellate cells (HSCs), known as a major cell inducing liver steatosis and fibrosis, can be killed by liver NK cells, which could be suppressed by chronic alcohol consumption. In this review, with the view of liver as predominant innate immune organ, we describe the pathogenesis of ALD in which what roles of innate immune cells are and how they are interacting with HSCs.