• Herbal Formula Science
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• v.22 no.1
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• pp.167-176
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• 2014

Objectives : This study investigated the improvement effects of Gangjihwan (DF) and combination of Gangjihwan and Gamisochehwan (GSH) on nonalcoholic fatty liver disease in a high fat diet-induced obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into five groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and atorvastatin, DF, and DF+GSH groups given a high fat diet with atorvastatin (10 mg/kg), DF (40 mg/kg), and DF+GSH (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, blood lipid markers, ALT concentrations, liver weight and histology were examined. Results : 1. Body weight gain was significantly decreased in DF, DF+GSH and atorvastatin groups compared with control. The extent of decreases was eminent in DF+GSH group. 2. Circulating concentrations of total cholesterol, HDL-cholesterol and LDL-cholesterol were decreased in DF, DF+GSH and atorvastatin groups compared with control. The decreases were significant in DF+GSH and atorvastatin groups. 3. Liver weights were decreased in DF, DF+GSH and atorvastatin groups compared with control. In particular, liver weight was significantly reduced only in DF+GSH group. 4. Hepatic lipid accumulation was significantly decreased in DF, DF+GSH and atorvastatin groups compared with control, and the magnitude of which was more effective in DF+GSH group than in DF-only group. 5. Circulating ALT concentrations were decreased in DF, DF+GSH and atorvastatin compared with control, but ALS levels were significantly reduced only in DF+GSH group. Conclusions : In conclusion, these results suggest that DF decreases body weight gain, improves blood lipid metabolism, and reduces liver weight and hepatic lipid accumulation, contributing to the improvement of nonalcoholic fatty liver disease. In addition, these effects were more effective in DF+GSH combination group than in DF-only group.

• Herbal Formula Science
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• v.22 no.1
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• pp.113-122
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• 2014

Objectives : This study investigated the improvement effects of Pakistani (DF-a) and Chinese Ephedra herba-containing Gangjihwan (DF-b) on nonalcoholic fatty liver disease in a high fat diet-induced obese mouse model. Methods : Eight-week-old C57BL/6N mice were divided into five groups: a normal lean group given a standard diet, an obese control group given a high fat diet, and atorvastatin, DF-a, and DF-b groups given a high fat diet with atorvastatin (10 mg/kg), DF-a (80 mg/kg), and DF-b (80 mg/kg), respectively. After 8 weeks of treatment, body weight gain, blood lipid markers, ALT concentrations, liver weight and histology were examined. Results : 1. Body weight gain was significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control. The extent of decreases was eminent in DF-a group. 2. Circulating concentrations of total cholesterol and LDL-cholesterol were significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control. The decreases were most effective in atorvastatin group. 3. Liver weights were decreased in DF-a, DF-b, and atorvastatin groups compared with control. In particular, liver weight was significantly reduced in DF-b group. 4. Hepatic lipid accumulation was significantly decreased in DF-a, DF-b, and atorvastatin groups compared with control, and the magnitude of which was most effective in DF-b group. 5. Circulating ALT concentrations were decreased in DF-a, DF-b, and atorvastatin groups compared with control, but ALS levels were significantly reduced only in DF-b group. Conclusions : In conclusion, these results suggest that DF-a and DF-b decrease body weight gain, improve blood lipid metabolism, and reduce liver weight and hepatic lipid accumulation, contributing to the improvement of nonalcoholic fatty liver disease. In addition, these effects were similar between Pakistani and Chinese Ephedra herba-containing Gangjihwan.

• Journal of Ginseng Research
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• v.42 no.4
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• pp.419-428
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• 2018

Background: Despite the large number of studies on ginseng, pharmacological activities of ginseng seed oil (GSO) have not been established. GSO is rich in unsaturated fatty acids, mostly oleic and linoleic acids. Unsaturated fatty acids are known to exert a therapeutic effect in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effect and underlying mechanisms of GSO against NAFLD using in vitro and in vivo models. Methods: In vitro lipid accumulation was induced by free fatty acid mixture in HepG2 cells and by 3 wk of high fat diet (HFD)-feeding in Sprague-Dawley rats prior to hepatocyte isolation. The effects of GSO against diet-induced hepatic steatosis were further examined in C57BL/6J mice fed a HFD for 12 wk. Results: Oil Red O staining and intracellular triglyceride levels showed marked accumulation of lipid droplets in both HepG2 cells and rat hepatocytes, and these were attenuated by GSO treatment. In HFD-fed mice, GSO improved HFD-induced dyslipidemia and hepatic insulin resistance. Increased hepatic lipid contents were observed in HFD-fed mice and it was lowered in GSO (500 mg/kg)-treated mice by 26.4% which was evident in histological analysis. Pathway analysis of hepatic global gene expression indicated that GSO increased the expression of genes associated with ${\beta}$-oxidation (Ppara, Ppargc1a, Sirt1, and Cpt1a) and decreased the expression of lipogenic genes (Srebf1 and Mlxipl), and these were confirmed with reverse transcription and quantitative polymerase-chain reaction. Conclusion: These findings suggest that GSO has a beneficial effect on NAFLD through the suppression of lipogenesis and stimulation of fatty acid degradation pathway.

• Clinical and Experimental Pediatrics
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• v.62 no.12
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• pp.450-455
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• 2019

Background: Lipid accumulation product (LAP) is associated with the presence and severity of nonalcoholic fatty liver disease (NAFLD) in adults. Purpose: Here we evaluated the ability of LAP to predict NAFLD in obese children. Methods: Eighty obese children (38 girls; age 6-18 years) were included. Anthropometric measurements and biochemical values were obtained from the patients' medical records. LAP was calculated as [waist circumference (WC) (cm) - 58]×triglycerides (mmol/L) in girls; [WC (cm) - 65]×triglycerides (mmol/L) in boys. The minLAP and adjLAP were described (3% and 50% of WC values, respectively) and the total/high-density lipoprotein cholesterol index (TC/HDL-C) was calculated. NAFLD was observed on ultrasound, and patients were divided into 3 groups by steatosis grade (normal, grade 0; mild, grade 1; moderate-severe, grade 2-3). The area under the curve (AUC) and appropriate index cutoff points were calculated by receiver operator characteristic analysis. Results: LAP was positively correlated with puberty stage (rho=0.409; P<0.001), fasting insulin (rho= 0.507; P<0.001), homeostasis model assessment of insulin resistance (rho=0.470; P<0.001), uric acid (rho=0.522; P<0.001), and TC/HDL-C (rho=0.494; P<0.001) and negatively correlated with HDL-C (rho=-3.833; P<0.001). LAP values could be used to diagnose hepatosteatosis (AUC=0.698; P=0.002). The LAP, adjLAP, and minLAP cutoff values were 42.7 (P=0.002), 40.05 (P=0.003), and 53.47 (P= 0.08), respectively. For LAP, the differences between the normal and mild groups (P=0.035) and the normal and moderate-severe groups were statistically significant (P=0.037), whereas the difference between the mild and moderate-severe groups was not (P>0.005). There was a statistically significant difference between the normal and mild groups for adjLAP (P=0.043) but not between the other groups (P>0.005). There was no significant intergroup difference in minLAP (P>0.005). Conclusion: LAP is a powerful and easy tool to predict NAFLD in childhood. If LAP is ≥42.7, NAFLD should be suspected. This is the first study to assess LAP diagnostic accuracy for childhood obesity.

• 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.

• Nutrition Research and Practice
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• v.9 no.4
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• pp.350-357
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• 2015

BACKGROUND/OBJECTIVES: The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased worldwide in parallel with overnutrition characterized by high-fat and high-carbohydrate intake. Our objective was to establish, in 16 weeks, a model of NAFLD in Wistar pathogen-free rats following four dietary types. MATERIALS/METHODS: Forty (6 weeks old) healthy Wistar male rats, weighing an average of 150 g were randomly divided into four groups of ten and assigned a diet with the same quantity (15 g/rat/day), but with different composition. The moderate-fat (MF) group was fed a moderate-fat diet (31.5% fat and 50% carbohydrates), the high-fat (HF) group was fed a fat-rich diet (51% fat), the high-sucrose (HS) group and the high-fructose (HFr) group were fed a carbohydrate-rich diet (61%). The carbohydrate contents of the HS group was composed of 60.3% sucrose while that of the HFr group was composed of 59.3% fructose. RESULTS: At week 16, the HF group had the highest percentage of cells enriched in fat (40%) and the highest weight and liver weight (P < 0.05). The HFr group showed significantly higher levels of serum triglycerides, alanine aminotransferase and adiponectin at week 16 as compared to week 1 (P < 0.05). CONCLUSIONS: The 15 g/rat/day diet composed of 51% fat or 61% carbohydrates enriched mainly in fructose may induce characteristics of NAFLD in rats.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.24 no.6
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• pp.518-527
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• 2021

Purpose: The incidence of hepatic steatosis among children has been increasing; however, data distinguishing simple steatosis from a more complex disorder are lacking. Methods: This study identified the etiologies resulting in hepatic steatosis through a retrospective review of pediatric liver biopsies performed in the last 10 years. A total of 158 patients with hepatic steatosis proven by histopathological evaluation were enrolled in the study, and baseline demographic features, anthropometric measurements, physical examination findings, laboratory data, ultrasonographic findings, and liver histopathologies were noted. Results: The two most common diagnoses were inborn errors of metabolism (IEM) (52.5%) and nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) (29.7%). The three most common diseases in the IEM group were glycogen storage disorders, Wilson's disease, and mitochondrial disease. The rates of consanguineous marriage (75.6%; odds ratio [OR], 26.040) and positive family history (26.5%; OR, 8.115) were significantly higher (p=0.002, p<0.001, respectively) in the IEM group than those in the NAFLD/NASH group. Younger age (p=0.001), normal anthropometric measurements (p=0.03), increased aspartate aminotransferase levels (p<0.001), triglyceride levels (p=0.001), and cholestatic biochemical parameters with disrupted liver function tests, as well as severe liver destruction of hepatic architecture, cholestasis, fibrosis, and nodule formation, were also common in the IEM group. Conclusion: Parents with consanguinity and positive family history, together with clinical and biochemical findings, may provide a high index of suspicion for IEM to distinguish primary steatosis from the consequence of a more complex disorder.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.6
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• pp.459-466
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• 2019

Dipeptidyl peptidase (DPP)-4 inhibitors, or gliptins, are a class of oral hypoglycemic drugs that have been widely used as a second-line treatment for type 2 diabetes. Gliptins, which were introduced for clinical use a decade ago, have been shown to be beneficial against nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NASH) in animals and humans. Cenicriviroc (CVC), a dual antagonist of C-C chemokine receptor type 2 and 5, is currently under investigation against NASH and fibrosis. It was previously discovered that evogliptin (EVO) reduces hepatic steatosis in diet-induced obese animals but the effectiveness of EVO on NASH remains unexplored. Here, we compared the effectiveness of EVO and CVC against NASH and fibrosis in mice fed a high-fat and high-fructose diet (HFHF). Biochemical and histological analyses showed that mice fed a HFHF for 20 weeks developed severe hepatic steatosis and inflammation with mild fibrosis. Administration of EVO (0.2% wt/wt) for the last 8 weeks of HFHF feeding significantly reduced hepatic triglyceride accumulation, inflammation, and fibrosis as well as restored insulin sensitivity, as evidenced by lowered plasma insulin levels and the improvement in insulin tolerance test curves. Treatment of mice with CVC (0.1% wt/wt) inhibited hepatic inflammation and fibrogenesis with similar efficacy to that of EVO, without affecting hepatic steatosis. CVC treatment also reduced plasma insulin concentrations, despite no improvement in insulin tolerance. In conclusion, EVO administration efficiently ameliorated the development of NASH and fibrosis in HFHF-fed mice, corroborating its therapeutic potential.

• The Korea Journal of Herbology
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• v.29 no.2
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• pp.23-31
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• 2014

Objectives : This study was undertaken to verify the effects of Massa Medicata Fermentata (MMF) on nonalcoholic fatty liver disease (NAFLD) using high fat diet-fed male mice. Methods : Fifty four male C57BL/6N mice (age matched) were used for all experiments. Nine standard chow diet-fed mice were used as normal group and forty five high fat diet-fed obese mice were randomly divided into 5 groups: control, atorvastatin-10mg/kg, MMF(1)-62.5mg/kg, MMF(2)-125mg/kg and MMF(3)-250mg/kg. After all groups were treated with several kinds of diets for 8 weeks, we measured body weight gain, adipose tissue weights, plasma lipid and glucose metabolism, visceral organ weights, histological analysis for liver on the mice. Results : MMF-treated mice had lower body weight gain compared with controls. Among MMF-treated mice, the effect was magnified in MMF(2). MMF(3)-treated mice had lower blood plasma total cholesterol (TC) and glucose level compared with controls. MMF decreased hepatic lipid accumulation, liver fibrosis and liver inflammation of mice compared with controls. The effects was maximized in MMF(2) and atorvastatin. Blood plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), ${\gamma}$-glutamyltransferase (${\gamma}$-GT) concentrations tends to be decreased by MMF compared with controls. Blood plasma AST, ALT, ${\gamma}$-GT concentrations and organ weights were not changed by MMF, indicating that all three kinds of MMF do not show any hepatotoxicity. Conclusions : These results suggest that MMF improves NAFLD by reducing body weight gain, hepatic lipid accumulation, liver fibrosis, liver inflammation.

• KOREAN ASSOCIATION OF OCCUPATIONAL HEALTH NURSES
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• v.19 no.1
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• pp.18-24
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• 2012

동서양을 망라하여 전 세계적으로 비알코올성 지방간(Nonalcoholic fatty liver disease[NAFLD])의 발생률은 증가추세에 있다. NAFLD는 간에 중성지방(triacylglyceride)이 비정상적으로 축적되어 발생하지만, 사람에 따라서는 간조직에 염증반응이 초래되고, 심지어 간경화, 간암으로까지 진행되기도 한다. NAFLD의 원인이 비만, 인슐린내성과 같은 대사증후군과 연관되기는 하지만, 정확한 병리기전은 아직 규명되지 않았다. 따라서, 치료방법도 충분히 개발되지 못하고 있다. 그럼에도 불구하고, NAFLD에 있어 분명한 점은, 예방과 악화방지가 가능하다는 사실이다.