• Journal of Ginseng Research
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• v.48 no.2
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• pp.122-128
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• 2024

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic fat accumulation, while nonalcoholic steatohepatitis (NASH) is an advanced form of NAFLD characterized by hepatic inflammation, fibrosis, and liver injury, resulting in liver cirrhosis and hepatocellular carcinoma (HCC). Given the evidence that ginseng and its major bioactive components, ginsenosides, have potent anti-adipogenic, anti-inflammatory, anti-oxidative, and anti-fibrogenic effects, the pharmacological effect of ginseng and ginsenosides on NAFLD and NASH is noteworthy. Furthermore, numerous studies have successfully demonstrated the protective effect of ginseng on these diseases, as well as the underlying mechanisms in animal disease models and cells, such as hepatocytes and macrophages. This review discusses recent studies that explore the pharmacological roles of ginseng and ginsenosides in NAFLD and NASH and highlights their potential as agents to prevent and treat NAFLD, NASH, and liver diseases caused by hepatic steatosis and inflammation.

• IMMUNE NETWORK
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• v.16 no.3
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• pp.147-158
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• 2016

The liver lies at the intersection of multiple metabolic pathways and consequently plays a central role in lipid metabolism. Pathological disturbances in hepatic lipid metabolism are characteristic of chronic metabolic diseases, such as obesity-mediated insulin resistance, which can result in nonalcoholic fatty liver disease (NAFLD). Tissue damage induced in NAFLD activates and recruits liver-resident and non-resident immune cells, resulting in nonalcoholic steatohepatitis (NASH). Importantly, NASH is associated with an increased risk of significant clinical sequelae such as cirrhosis, cardiovascular diseases, and malignancies. In this review, we describe the immunopathogenesis of NASH by defining the known functions of immune cells in the progression and resolution of disease.

• Toxicological Research
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• v.33 no.1
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• pp.31-41
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• 2017

Side stream cigarette smoke (SSCS) is known to be as harmful and hazardous to human health as is active smoking. In this study, we investigated the relationship between the exposure to SSCS and its stimulatory and subacute effects on the progression of non-alcoholic steatohepatitis (NASH). A methionine and choline-deficient plus high fat (MCDHF) diet was administered to C57BL/6 mice for 6 weeks. During the first three weeks of MCDHF diet feeding, each diet group was exposed to SSCS (0, 20, $40{\mu}g/L$) or fresh air for 2 hrs per day and 5 days per week. Additional experiments were performed by increasing the concentration (0, 30, $60{\mu}g/L$) and exposure time (6 hours per day) of SSCS. According to histopathologic analysis and serum levels of Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST), there were no differences in hepatic fat deposition, fibrosis, apoptosis or liver damage in MCDHF-fed mice based on SSCS exposure. There were also no differences in the expression of inflammation-, oxidative stress- or fibrosis-related genes between MCDHF-fed mice with or without SSCS exposure. Therefore, it is concluded that SSCS with current exposure amounts does not have additive detrimental effects on the early stage of NASH.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.18 no.2
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• pp.108-114
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• 2015

Purpose: The aim of this study is to evaluate the relationship between abdominal subcutaneous fat thickness measured by ultrasonography (US) and serum lipid profile and liver transaminases in obese children. Methods: One hundred and sixty-six children diagnosed with obesity from May 2001 to December 2013 were included in this study. Data on serum lipid profile and liver transaminases were collected from clinical records. Abdominal subcutaneous fat thickness and grade of hepatic steatosis were evaluated by US. Results: Of the 166 children, 107 were diagnosed with hepatic steatosis by US, 46 with grade I, 56 with grade II, and five children with grade III. According to the grade of hepatic steasosis, the average values of midline abdominal subcutaneous fat thickness and right flank abdominal subcutaneous fat thickness measured $2.9{\pm}0.8cm$ and $1.9{\pm}0.7cm$ in the normal group, $3.3{\pm}0.8cm$ and $2.0{\pm}0.7cm$ in grade I, $3.8{\pm}0.8cm$ and $2.3{\pm}0.8cm$ in grade II, and $4.1{\pm}0.8cm$ and $2.8{\pm}1.4cm$ in grade III, respectively. Abdominal subcutaneous fat thickness correlated with grade of hepatic steatosis (p<0.01). In addition, abdominal subcutaneous fat thickness correlated with concentration of serum lipids and liver transaminases in the age group of 12-14 years (p<0.01). Conclusion: Abdominal subcutaneous fat thickness measured by US can be used as a reliable predictor of possible hyperlipidemia and steatohepatitis in children, especially during the adolescent stage.

• 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.

• Journal of Ginseng Research
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• v.46 no.1
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• pp.126-137
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• 2022

Background: Nonalcoholic steatohepatitis (NASH) is one of the main chronic liver diseases. NASH is identified by lipid accumulation, inflammation, and fibrosis. Jinan Red Ginseng (JRG) and licorice have been widely used because of their anti-inflammatory and hepatoprotective effects. Hence, this study assessed JRG and licorice extract mixtures' effects on NASH progression. Methods: Palmitic acid (PA) and the western diet (WD) plus, high glucose-fructose water were used to induce in vitro and in vivo NASH. Mice were orally administered with JRG-single (JRG-S) and JRG-mixtures (JRG-M; JRG-S + licorice) at 0, 50, 100, 200 or 400 mg/kg/day once a day during the last half-period of diet feeding. Results: JRG-S and JRG-M reduced NASH-related pathologies in WD-fed mice. JRG-S and JRG-M consistently decreased the mRNA level of genes related with inflammation, fibrosis, and lipid metabolism. The treatment of JRG-S and JRG-M also diminished the SREBP-1c protein levels and the p-AMPK/AMPK ratio. The FAS protein levels were decreased by JRG-M treatment both in vivo and in vitro but not JRG-S. Conclusion: JRG-M effectively reduced lipogenesis by modulating AMPK downstream signaling. Our findings suggest that this mixture can be used as a prophylactic or therapeutic alternative for the remedy of NASH.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.25 no.3
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• pp.240-250
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• 2022

Purpose: This study aimed to examine the advantages and usefulness of transient elastography (Fibroscan^®) in diagnosing non-alcoholic steatohepatitis in children and adolescents compared to those of abdominal computed tomography and liver ultrasonography. Methods: Forty-six children and adolescent participants aged between 6 and 16 years who underwent transient elastography (Fibroscan^®) as well as liver ultrasonography or abdominal computed tomography were included. Thirty-nine participants underwent liver ultrasonography and 11 underwent computed tomography. The physical measurements, blood test results, presence of metabolic syndrome, and the degree of liver steatosis and liver fibrosis were analyzed, and their correlations with transient elastography (Fibroscan^®), abdominal computed tomography, and liver ultrasonography, as well as the correlations between examinations, were analyzed. Results: Thirty-six participants (78.3%) were boys, and the mean age was 12.29±2.57 years, with a mean body mass index of 27.88±4.28. In the 46 participants, the mean values for aspartate aminotransferase, alanine aminotransferase, and total bilirubin were 89.87±118.69 IU/L, 138.54±141.79 IU/L, and 0.77±0.61 mg/dL, respectively. Although transient elastography (Fibroscan^®) and abdominal computed tomography grading had a statistically significant positive correlation with aspartate aminotransferase and alanine aminotransferase values, the correlations between the results of grading performed by transient elastography (Fibroscan^®), abdominal computed tomography, and liver ultrasonography were not statistically. Conclusion: We confirmed that each examination was correlated with the results of some blood tests, suggesting the usefulness and possibility of diagnosis and treatment of steatohepatitis mediated by transient elastography (Fibroscan^®) in the department of pediatrics.

• Journal of Nutrition and Health
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• v.56 no.6
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• pp.589-601
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• 2023

Purpose: Baicalein, a natural flavone found in herbs, exhibits diverse biological activities. Nonalcoholic steatohepatitis (NASH) is an irreversible condition often associated with a poor prognosis. This study aimed to evaluate the effects of baicalein on the development of NASH in mice. Methods: Male C57BL/6J mice were randomly divided into four groups. Three groups were fed a methionine-choline-deficient (MCD) diet to induce NASH and were simultaneously treated with baicalein (at doses of 50 and 100 mg/kg) or vehicle only (sodium carboxymethylcellulose) through oral gavage for 4 weeks. The control group was fed a methionine-choline-sufficient (MCS) diet without the administration of baicalein. Results: The baicalein treatment significantly reduced serum levels of alanine aminotransferase and aspartate aminotransferase, suggestive of reduced liver damage. Histological analysis revealed a marked decrease in nonalcoholic fatty liver activity scores induced by the MCD diet in the mice. Similarly, baicalein treatment at both doses significantly attenuated the degree of hepatic fibrosis, as examined by Sirius red staining, and hepatocellular death, as examined by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Baicalein treatment attenuated MCD-diet-induced lipid peroxidation, as evidenced by lower levels of hepatic malondialdehyde and 4-hydroxynonenal, demonstrating a reduction in oxidative stress resulting from lipid peroxidation. Moreover, baicalein treatment suppressed hepatic protein levels of 12-lipoxygenase (12-Lox) induced by the MCD diet. In contrast, baicalein enhanced the activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Additionally, baicalein treatment significantly reduced hepatic non-heme iron concentrations and hepatic ferritin protein levels in mice fed an MCD diet. Conclusion: To summarize, baicalein treatment suppresses hepatic lipid peroxidation, 12-Lox expression, and iron accumulation, all of which are associated with the attenuation of NASH progression.

• 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 Physiology & Pathology in Korean Medicine
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• v.26 no.5
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• pp.724-731
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• 2012

This study was designed to elucidate whether combination with Korean red ginseng and Morus alba L. (MPM), traditional treatment for diabetes, ameliorates on high fructose-induced steatohepatitis and vascular inflammation. Animals were divided into four groups; Control receiving tap water, fructose-fed, rosiglitazone-treated fructose-fed rats, and MPM-treated fructose-fed rats both receiving supplemented with 60% fructose (n=10). The MPM or rosiglitazone groups initially received a high-fructose diet alone for 8 weeks, with supplementation with MPM or rosiglitazone, peroxisome proliferators-activated receptor gamma ($PPAR{\gamma}$) agonist, occurring during the final 6 weeks. Treatment with MPM significantly prevented the increase in c-reactive protein (CRP) levels in the high fructose group. MPM suppressed high fructose diet-induced vascular inflammation marker expression such as intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin. MPM also reduced intima/media thickness of thoracic aorta. Histologic observation and oil red O staining demonstrated hepatic tissue damage and lipid accumulation were severe in high fructose group. Treatment with MPM ameliorated hepatic tissue morphology with minimized steatosis. In addition, MPM attenuated hepatitis by inhibition of monocyte chemoattractant protein-1 (MCP-1) expression. MPM-fed group showed lower serum GOT and GPT levels comparing with high fructose group. MPM and rosiglitazone (positive control) significantly decreased the size of epididymal adipocytes. Taken together, the administration of MPM inhibited high fructose-induced steatohepatitis and vascular inflammation. These results suggested that MPM is useful in the prevention or treatment of metabolic syndrome-related disorders such as fatty acid metabolism and vascular homeostasis.