• The Korea Journal of Herbology
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• v.33 no.5
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• pp.1-8
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• 2018

Objectives : The aim of this study is to investigate the preventive effect of Puerariae Flos ethanol extract (PE) on methionin and choline deficient (MCD)-diet-induced Nonalcoholic fatty liver disease (NAFLD) in C57BL/6J mice. Methods : In the in vivo experiments, C57BL/6J mice were divided into 4 groups; Normal group, Control group, MCD+PE 100 group, and MCD+PE 300 group. After 4 weeks, body weight, liver weight, biochemical parameters for liver function test, histological changes, reverse transcription polymerase chain reaction (RT-PCR), and Western blot were assessed. Results : Mice lost body weight with the MCD-diet and the MCD+PE 100 group and MCD+PE 300 groups lost less than the control group, though showed no statistical significance. Liver weights were decreased by the MCD diet, but MCD+PE 300 groups were increased significantly. In the liver function test, all the values were decreased with the MCD-diet, MCD+PE 100 group and MCD+PE 300 groups were increased significance. In histological findings of the livers, MCD-diet induced severe fatty accumulation in the livers, but this fatty change was reduced in the MCD+PE 100 group and MCD+PE 300 groups was inhibited respectively. In lipid accumulation factors (such as SREBP-1c, $C/EBP{\alpha}$, PPAR-${\gamma}$), MCD+PE 100 group and MCD+PE 300 groups showed inhibitory effect on liver lipogenesis by reducing associated gene expressions caused by MCD diet. Conclusions : We were able to know that Puerariae Flos ethanol extract (PE) shown hepatoprotective effects via a decrease on the hepatic lipogenesis factors in the experimental NAFLD Models.

• BMB Reports
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• v.42 no.8
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• pp.475-481
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• 2009

Emerging data demonstrate pivotal roles for brain insulin resistance and insulin deficiency as mediators of cognitive impairment and neurodegeneration, particularly Alzheimer's disease (AD). Insulin and insulin-like growth factors (IGFs) regulate neuronal survival, energy metabolism, and plasticity, which are required for learning and memory. Hence, endogenous brain-specific impairments in insulin and IGF signaling account for the majority of AD-associated abnormalities. However, a second major mechanism of cognitive impairment has been linked to obesity and Type 2 diabetes (T2DM). Human and experimental animal studies revealed that neurodegeneration associated with peripheral insulin resistance is likely effectuated via a liver-brain axis whereby toxic lipids, including ceramides, cross the blood brain barrier and cause brain insulin resistance, oxidative stress, neuro-inflammation, and cell death. In essence, there are dual mechanisms of brain insulin resistance leading to AD-type neurodegeneration: one mediated by endogenous, CNS factors; and the other, peripheral insulin resistance with excess cytotoxic ceramide production.

• Journal of Life Science
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• v.21 no.12
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• pp.1795-1803
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• 2011

Non-alcoholic fatty liver disease accompanies the rise in the prevalence of obesity, diabetes and the tendency toward high-fat dietary habits. Specifically, the higher prevalence of non-alcoholic fatty liver disease in men and postmenopausal women seems to be caused by the protective effects of estrogen against liver fibrosis, or lack thereof. There are no effective preventive therapies for liver diseases because the mechanisms underlying the progression of fatty liver diseases to chronic liver diseases and the protective effects of estrogen against fibrogenesis remain unclear. Recently, it has been reported that the hedgehog signaling pathway plays an important role in the progression of chronic liver diseases. Hedgehog, a morphogen regulating embryonic liver development, is expressed in injured livers but not in adult healthy livers. The level of hedgehog expression parallels the stages of liver diseases. Hedgehog induces myofibroblast activation and hepatic progenitor cell proliferation and leads to excessive liver fibrosis, whereas estrogen inhibits the activation of hepatic stellate cells to myofibroblasts and prevents liver fibrosis. Although the mechanism underlying the opposing actions of hedgehog and estrogen on liver fibrosis remain unclear, the suppressive effects of estrogen on the expression of osteopontin, a profibrogenic extracellular matrix protein and cytokine, and the inductive effects of hedgehog on osteopontin transcription suggest that estrogen and hedgehog are associated with liver fibrosis regulation. Therefore, further research on the estrogen-mediated regulatory mechanisms underlying the hedgehog-signaling pathway can identify the mechanism underlying liver fibrogenesis and contribute to developing therapies for preventing the progression of fibrosis to chronic liver diseases.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.429-439
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• 2023

Background: The incidence and clinical importance of nonalcoholic fatty liver disease (NAFLD) has emerged. However, effective therapeutic strategies for NAFLD have yet to be found. Panax ginseng (P. ginseng) is a traditional herb in Eastern Asia with therapeutic effects in many chronic disorders. However, the precise effects of ginseng extract on NAFLD are currently unknown. In present study, the therapeutic effects of Rg3-enriched red ginseng extract (Rg3-RGE) on the progression of NAFLD were explored. Methods: Twelve-week-old C57BL/6 male mice were fed a chow or western diet supplemented with high sugar water solution with or without Rg3-RGE. Histopathology, immunohistochemistry, immunofluorescence, serum biochemistry, western blot analysis, and quantitative RT-PCR were used for in vivo experiment. Conditionally immortalized human glomerular endothelial cell (CiGEnC) and primary liver sinusoidal endothelial cells (LSECs) were used for in vitro experiments. Results: Eight weeks of Rg3-RGE treatment significantly attenuated the inflammatory lesions of NAFLD. Furthermore, Rg3-RGE inhibited the inflammatory infiltrate in liver parenchyma and the expression of adhesive molecules to LSECs. Moreover, the Rg3-RGE exhibited similar patterns on the in vitro assays. Conclusion: The results demonstrate that Rg3-RGE treatment ameliorates NAFLD progression by inhibiting chemotaxis activities in LSECs.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.19 no.3
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• pp.199-206
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• 2016

Purpose: To analyze the associations among the degrees of nonalcoholic fatty liver disease (NAFLD) by ultrasonography and metabolic syndrome, degrees of obesity in children, and degrees of parental obesity. Methods: A total of 198 children with obesity who visited a pediatric obesity clinic were prospectively enrolled in this study. The severity of NAFLD based on ultrasonography was classified into no, mild, moderate, or severe NAFLD group. The degree of obesity based on the percentage over standard weight for height per sex was classified into mild, moderate, or severe. Results: Of 132 patients evaluated for the degree of NAFLD and metabolic syndrome, the p-value of correlation between the two factors was 0.009. Therefore, metabolic syndrome might significantly affect the degree of NAFLD. Of 158 patients evaluated for the degree of NAFLD and the degree of obesity, the p-value of correlation between the two factors was 0.122. Of 154 patients evaluated for the degree of obesity and father's obesity, the p-value was 0.076. Of 159 patients evaluated for the degree of obesity and mother's obesity, the p-value was 0.000, indicating that mother's obesity could significantly affect the degree of obesity in children. Of 142 patients evaluated for the degree of obesity and metabolic syndrome, the p-value was 0.288. Conclusion: Metabolic syndrome might significantly affect the degree of nonalcoholic fatty liver in children. In addition, mother's obesity might be a significant factor that affects the degree of obesity in children.

• Nutrition Research and Practice
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• v.15 no.4
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• pp.431-443
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• 2021

BACKGROUND/OBJECTIVES: Nobiletin (NOB), a citrus flavonoid, is reported to have beneficial effects on cardiovascular and metabolic health. However, there is limited research investigating the effect of long-term supplementation with low-dose NOB on high-cholesterol diet (HCD)-induced hypercholesterolemia and non-obese nonalcoholic fatty liver disease (NAFLD). Therefore, we investigated the influence of NOB on hypercholesterolemia and NAFLD in HCD-fed mice. SUBJECTS/METHODS: C57BL/6J mice were fed a normal diet (ND) or HCD (35 kcal% fat, 1.25% cholesterol, 0.5% cholic acid) with or without NOB (0.02%) for 20 weeks. RESULTS: HCD feeding markedly reduced the final body weight compared to ND feeding, with no apparent energy intake differences. NOB supplementation suppressed HCD-induced weight loss without altering energy intake. Moreover, NOB significantly decreased the total cholesterol (TC) levels and the low-density lipoprotein (LDL)/very-LDL-cholesterol to TC ratio, and increased the high-density lipoprotein-cholesterol/TC ratio in plasma, compared to those for HCD feeding alone. The plasma levels of inflammatory and atherosclerosis markers (C-reactive protein, oxidized LDL, interleukin [IL]-1β, IL-6, and plasminogen activator inhibitor-1) were significantly lower, whereas those of anti-atherogenic adiponectin and paraoxonase were higher in the NOB-supplemented group than in the HCD control group. Furthermore, NOB significantly decreased liver weight, hepatic cholesterol and triglyceride contents, and lipid droplet accumulation by inhibiting messenger RNA expression of hepatic genes and activity levels of cholesterol synthesis-, esterification-, and fatty acid synthesis-associated enzymes, concomitantly enhancing fatty acid oxidation-related gene expression and enzyme activities. Dietary NOB supplementation may protect against hypercholesterolemia and NAFLD via regulation of hepatic lipid metabolism in HCD-fed mice; these effects are associated with the amelioration of inflammation and reductions in the levels of atherosclerosis-associated cardiovascular markers. CONCLUSIONS: The present study suggests that NOB may serve as a potential therapeutic agent for the treatment of HCD-induced hypercholesterolemia and NAFLD.

• Experimental and Molecular Medicine
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• v.50 no.12
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• pp.2.1-2.12
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• 2018

Glucagon-like peptide-1 (GLP-1) has a broad spectrum of biological activity by regulating metabolic processes via both the direct activation of the class B family of G protein-coupled receptors and indirect nonreceptor-mediated pathways. GLP-1 receptor (GLP-1R) agonists have significant therapeutic effects on non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) in animal models. However, clinical studies indicated that GLP-1 treatment had little effect on hepatic steatosis in some NAFLD patients, suggesting that GLP-1 resistance may occur in these patients. It is well-known that the gut metabolite sodium butyrate (NaB) could promote GLP-1 secretion from intestinal L cells. However, it is unclear whether NaB improves hepatic GLP-1 responsiveness in NAFLD. In the current study, we showed that the serum GLP-1 levels of NAFLD patients were similar to those of normal controls, but hepatic GLP-1R expression was significantly downregulated in NAFLD patients. Similarly, in the NAFLD mouse model, mice fed with a high-fat diet showed reduced hepatic GLP-1R expression, which was reversed by NaB treatment and accompanied by markedly alleviated liver steatosis. In addition, NaB treatment also upregulated the hepatic p-AMPK/p-ACC and insulin receptor/insulin receptor substrate-1 expression levels. Furthermore, NaB-enhanced GLP-1R expression in HepG2 cells by inhibiting histone deacetylase-2 independent of GPR43/GPR109a. These results indicate that NaB is able to prevent the progression of NAFL to NASH via promoting hepatic GLP-1R expression. NaB is a GLP-1 sensitizer and represents a potential therapeutic adjuvant to prevent NAFL progression to NASH.

• The Journal of the Korea Contents Association
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• v.11 no.10
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• pp.342-348
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• 2011

The study aimed to compare the validity between the abdominal ultrasonographic(US) grading system of fatty liver and histologic grading system of fatty liver in living liver donor candidates. As the fatty liver is defined as pathologic total fat >10%, US validity was sensitivity 64.6%, specificity 68%, positive predictive value 76.8%, negative predictive value 54%. As the strict data handling on US grading normal, mild fatty liver are negative, moderate fatty liver is positive, US validity was sensitivity 26.8%, specificity 100%, positive predictive value 100%, negative predictive value 45.5%. ROC curve analysis according to different cut off value of liver-to-kidney brightness ratio was Area under ROC curve=0.859(95% CI=0.795~0.922, state variable= total fat 10%). There were statistically significant difference( p<0.001). Ultrasonography for the fatty diagnosis showed a high validity to predict the result of histology grade of fatty liver.

• Journal of Digital Convergence
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• v.13 no.7
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• pp.249-258
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• 2015

This study was conducted to determine the affecting factors among patients with drinking behavior of liver cirrhosis. Data were collected by questionnaire from 157 patients who were diagnosed with liver cirrhosis at a tertiary hospital located in D-city. Measurements included patients' demographic characteristics, clinical characteristics, disease-related of symptom experience, emotional-factors of anxiety-depression and social-factor of social support. Data were analyzed using t-test, and logistic regression analyses. The incidence rate of drinking behavior was 31.8%. Multivariate analysis revealed that smoking(yes), men, symptom experience, social support and anxiety were more likely to report high level of drinking behavior. Future research should consider managing drinking behavior as an essential component of comprehensive care for patients with liver cirrhosis.

• Biomedical Science Letters
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• v.10 no.2
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• pp.99-105
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• 2004

Liver and serum rhodanese activities were determined in acute ethanol intoxicated rats with extrahepatic cholestasis induced by common bile duct ligation (CBD) to manifest the biochemical background of alcohol drinking hazard under the hepatobiliary disease. Liver cytosolic and microsomal rhodanese activities and these Vmax values in CBD ligated rats with acute ethanol intoxication were found to be decreased much more than that in CBD ligation alone. However, the difference of Km value on above hepatic enzyme was not found between the experimental groups. On the other hand, serum rhodanese activity in CBD ligated rats with acute ethanol intoxication was greater increased more than that in CBD ligation alone. These results indicate that the biosynthesis of the hepatic rhodanese decreases and the serum rhodanese activity increases in cholestasis combined with acute ethanol intoxication, reflecting damage of aggravated hapatocytic membrane. Accordingly, the resulting data supported the fact that alcoholic drinks were enzymologically harmful to the hepatobiliary disease.