• 대한의생명과학회지
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• 제23권2호
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• pp.144-153
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• 2017

It was demonstrated that Gangjihwan (DF), which is the herbal composition composed of Ephedra intermedia, Lithospermum erythrorhizon, and Rheum palmatum, inhibits obesity and hepatic steatosis in high fat diet (HFD)-fed obese mice. The aim of this study was to determine the effects of DF on visceral obesity, hepatic inflammation and fibrosis and the mechanism of actions involved in this process using in vivo and in vitro approaches. DF was extracted with water (DF-FW), 30% grain alcohol (DF-GA30), and 70% grain alcohol (DF-GA70). Administration of DF to HFD-fed control mice decreased visceral tissue mass and visceral adipocyte size without adverse effects. Visceral fat mass was decreased by DF-GA30 and DF-GA70, and visceral adipocyte size by all three DF extracts compared with obese control mice. Histological analysis revealed that three kinds of DF extracts reduced toluidine blue-stained mast cells and collagen accumulation in the liver, the extents of which were most eminent in DF-GA70-treated mice. DF-GA70 decreased the mRNA levels of the inflammation ($TNF{\alpha}$ and VCAM-1), fibrosis (${\alpha}-SMA$), and apoptosis (caspase 3) genes, but increasing the anti-apoptosis gene (Bcl-2) mRNA levels in the liver of obese control mice. Consistent with the in vivo data, GA-70 also altered the expression of inflammation genes ($TNF{\alpha}$ and MCP-1) in HepG2 cells. These results indicate that DF not only inhibits visceral obesity, but also ameliorates visceral obesity-induced hepatic inflammation and fibrosis and that this process may be mediated by regulating the hepatic expression of inflammatory and fibrogenic genes.

• 대한한방내과학회지
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• 제35권4호
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• pp.505-518
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• 2014

Objectives: This study was undertaken to investigate the effects of Gugijagami-bang (GGB) in a hyperlipidemic animal model induced by a high-fat diet using diverse biological methods. Methods: This study was to determine whether fractionated GGB extracts inhibit reactive oxygen species (ROS) and nitric oxide (NO) in RAW 264.7 cells. Hyperlipidemia was induced by a high-fat diet fed for 6 weeks. Total cholesterol, LDL cholesterol, HDL cholesterol, triglyceride, liver function and histologic change of liver were measured after oral administration of GGB. Results: 1. DPPH scavenging bow performance was increased in a concentration-dependent manner by GGB. 2. Compared to the control group, NO production (%) and ROS production (%) were decreased significantly by GGB. 3. Total-cholesterol, LDL-cholesterol, triglyceride were decreased significantly by GGB. 4. HDL cholesterol increased more than the control group, but not significantly. 5. In histopathologic examination, fatty liver (hepatic steatosis) was inhibited, almost no rounds of fat were observed in the liver. Conclusions: GGB would appear effective in the prevention and treatment of atherosclerosis, ischemic heart disease, other cardiovascular diseases caused by hyperlipidemia.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.203-209
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• 2008

The aim of this study was to investigate the hepatoprotective effect of $ACTIValoe^{(R)}$ N-931 complex, a mixture of Aloe vera and Silybum marianum, against acute liver injuries. Acute liver damages were induced by intraperitoneal injection of galactosamine (GalN, 700 mg/kg), naphthylisothiocyanate (ANIT, 40 mg/kg) and ethionine (500 mg/kg). $ACTIValoe^{(R)}$ N-931 (85, 170 and 340) was administered orally 48 h, 24 h, 2 h before and 6 h after the injection of hepatotoxins. At 24 h after GalN treatment the levels of serum aminotransferases and hepatic lipid peroxidation were significantly elevated, whereas hepatic glutathione, serum triglyceride (TG) and total cholesterol were decreased. These changes were attenuated by $ACTIValoe^{(R)}$ N-931 complex. The serum aminotransferase activities and total bilirubin significantly increased at 48 h after ANIT treatment, but were attenuated by $ACTIValoe^{(R)}$ N-931 complex. The bile flow was lower after ANIT treatment, which was restored by $ACTIValoe^{(R)}$ N-931 complex. $ACTIValoe^{(R)}$ N-931 complex reduced the ethionine-induced elevated hepatic TG contents. Histopathological analysis revealed that signs of liver injury were prominent at 24 h as result of ethionine injection, demonstrated by extensive areas of fatty change and microvesicular steatosis were observed around cells. These changes were attenuated by $ACTIValoe^{(R)}$ N-931 complex. Our results suggest that the $ACTIValoe^{(R)}$ N-931 complex has a protective effect on acute liver injury.

• Biomolecules & Therapeutics
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• 제18권3호
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• pp.336-342
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• 2010

Obesity-induced disorders contribute to the development of metabolic diseases such as insulin resistance, fatty liver diseases, and type 2 diabetes (T2D). In this study, we evaluated the hypoglycemic and hypolipidemic effects of aloe formula in high fat diet (HFD)-fed C57BL/6N mice. Male mice fed HFD for 28 weeks received a supplement of aloe formula, PAG, ALS, Aloe QDM, and an Aloe QDM complex for a further 8 weeks and were then compared with regular diet fed mice. After the experimental period, the blood glucose levels of the Aloe QDM complex-and PGZ-supplemented mice were significantly lower than those of the HFD-fed mice. Aloe formula, especially the Aloe QDM complex, and the PGZ treatment group profoundly affected the IPGTT and HOMA-IR. Immunochemistry was done for the morphological observation and the resulting sizes of adipocytes around the epididymis were significantly decreased when comparing the aloe formula-treated and HFD-fed groups. Further, aloe formula decreased mRNA expression of fatty acid synthesis enzymes and led to reduced hepatic steatosis in both liver and WAT. These results suggest that supplementation of Aloe QDM complex in the HFD-fed mice improved insulin resistance by lowering blood glucose levels and reducing adipocytes. Our data suggest that dietary aloe formula reduces obesity-induced glucose tolerance by suppressing fatty acid synthesis in the WAT and liver, both of which are important peripheral tissues affecting insulin resistance. The Aloe QDM complex could be used as a nutritional intervention against T2D.

• Nutrition Research and Practice
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• 제10권5호
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• pp.477-486
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• 2016

BACKGROUND/OBJECTIVES: Consumption of pine nut oil (PNO) was shown to reduce weight gain and attenuate hepatic steatosis in mice fed a high-fat diet (HFD). The aim of this study was to examine the effects of PNO on both intestinal and hepatic lipid metabolism in mice fed control or HFD. MATERIALS/METHODS: Five-week-old C57BL/6 mice were fed control diets containing 10% energy fat from either Soybean Oil (SBO) or PNO, or HFD containing 15% energy fat from lard and 30% energy fat from SBO or PNO for 12 weeks. Expression of genes related to intestinal fatty acid (FA) uptake and channeling (Cd36, Fatp4, Acsl5, Acbp), intestinal chylomicron synthesis (Mtp, ApoB48, ApoA4), hepatic lipid uptake and channeling (Lrp1, Fatp5, Acsl1, Acbp), hepatic triacylglycerol (TAG) lipolysis and FA oxidation (Atgl, Cpt1a, Acadl, Ehhadh, Acaa1), as well as very low-density lipoprotein (VLDL) assembly (ApoB100) were determined by real-time PCR. RESULTS: In intestine, significantly lower Cd36 mRNA expression (P<0.05) and a tendency of lower ApoA4 mRNA levels (P = 0.07) was observed in PNO-fed mice, indicating that PNO consumption may decrease intestinal FA uptake and chylomicron assembly. PNO consumption tended to result in higher hepatic mRNA levels of Atgl (P = 0.08) and Cpt1a (P = 0.05). Significantly higher hepatic mRNA levels of Acadl and ApoB100 were detected in mice fed PNO diet (P<0.05). These results suggest that PNO could increase hepatic TAG metabolism; mitochondrial fatty acid oxidation and VLDL assembly. CONCLUSIONS: PNO replacement in the diet might function in prevention of excessive lipid uptake by intestine and improve hepatic lipid metabolism in both control diet and HFD fed mice.

• Journal of Nutrition and Health
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• 제21권3호
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• pp.154-163
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• 1988

Effects of alchohol and fat content in a balanced diet on chemical composition and morphology of liver were investigated in growing rats. Fourth eight male rats of Sprague-Dawley strain weighing about 160g were divided into 4 groups ; high fat diet group, alcohol-administered high fat diet group, low fat diet group and alcohol-administered high fat diet group, low fat diet group and alcohol-administered low fat diet group. High and low fat diets supplied 30% and 12%, respectively, of total calorie intake from fat, and alcohol was given by adding ethanol in drinking waster at 10%. Diets contained adequate amounts of all nutrients required for rats, including lipotrpoic agents(choline and methionine) to minimize effects of factors other than alcohol on liver damage. Ratios of liver weight to body weight were statistically different among groups. Liver/dody weight ratios alcohol-administered rats were significantly higher than those of non-alcohol groups after 6 weeks treatment. Although total lipid and triglyceride per gram liver were increased in alcohol-administered rats, especially low fat diet fed rats, the values were not significantly different. Opticmicroscopical observation revealed increase in cell size and no change in morphology of liver. Examination of hepatocytes by electron microscopy showed that fat droplets were observed in all groups but enlarged in the alcohol-administered low fat diet fed rat. Contents of protein, cholesterol and phospholipid were not affected by alcohol consumption. The level of lipid peroxide was significantly lower in the livers of alcohol-administered rats than in the livers of non-alcohol groups. The results of this study indicate that even moderate alcohol drinking and dietary fat content did not affect any significant change in composition and morphology of liver until 6 week treatment but that even moderate alcohol drinking caused some signs of steatosis of liver.

• 대한한방내과학회지
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• 제37권3호
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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.

• Molecular & Cellular Toxicology
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• 제2권2호
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• pp.141-149
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• 2006

Tamoxifen (TAM), a non-steroidal anti estrogen anticancer drug and chemopreventive agent for breast cancer, have caused cholestasis in liver. The potent hepatocarcinogenicity of this drug has been reported. Methotrexate (MTX) is dihydrofolate reductase inhibitor which interfaces with the synthesis for urine nucleotide and dTMP. And it may cause atrophy, necrosis and steatosis in liver. These two anticancer drug have well-known hepatotoxicity. So, in this study we compare the gene expression pattern of antitumor agent TAM and MTX, using the cDNA microarray. We have used 4.8 K cDNA microarray to identify hepatotoxicity-related genes in 5-week-old male Sprague-Dawley (SD) rats. Confirm the pattern of gene expression, we have used Real time PCR for targeted gene. In the case of MTX, Protease related gene (Ctse, Ctsk) and Protein kinase (Pctk 1) have shown specific expression pattern. And in the case of TAM, apoptosis related gene (Pdcd 8) and signal transduction related gene (kdr) have significantly up regulated during treatment time. Gene related with growth factor, lipid synthesis, chemokins were significantly changed. From the result of this study, the information about influence of TAM and MTX to hepatoxicity will provide.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제18권3호
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• pp.168-174
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• 2015

Purpose: Recent studies have suggested that decreased serum potassium level may contribute to various metabolic disorders in adult patients including nonalcoholic fatty liver disease (NAFLD). We aimed to study the correlation between serum potassium levels and the histologic severity of NAFLD in children. Methods: Pediatric patients with biopsy-proven NAFLD were included in this study. Demographic, clinical, and histopathological data were obtained. Multivariable logistic regression analysis was used to assess whether potassium levels are associated with the presence of nonalcoholic steatohepatitis (NASH) or fibrosis after adjusting for possible confounders. A p-value <0.05 was considered statistically significant. Results: Among 125 biopsies, 49.6% (62) had evidence of NASH while 66.4% (83) had some degree of fibrosis (stage 1-3). Mean serum potassium was significantly lower in NASH group as compared to non-NASH group ($4.4{\pm}0.42mmoL/L$ vs. $4.8{\pm}0.21$, p<0.001). Higher potassium level had negative correlation with presence of steatosis, ballooning, lobular inflammation, fibrosis and NAFLD activity score (p<0.05). On multivariable analysis and after adjusting for the metabolic syndrome and insulin resistance, higher potassium level was significantly associated with lower likelihood of having a histological diagnosis of NASH on biopsy (odds ratio [OR], 0.12; 95% confidence interval [95% CI], 0.05-0.28; p<0.001). Similarly, the likelihood of having fibrosis decreases by 76% for every 0.5 mmoL/L increase in potassium (OR, 0.24; 95% CI, 0.11-0.54; p<0.001). Conclusion: Our study shows an inverse relationship between serum potassium levels and the presence of aggressive disease (NASH and fibrosis) in children with NAFLD.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제15권1호
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• pp.44-51
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• 2012

Purpose: Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) polymorphism has been suggested to play an important role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) in obese adults, and known to be a mediator of insulin resistance. In this study, we evaluated the role of TNF-${\alpha}$ promoter polymorphisms and insulin resistance in the development of NAFLD in obese children. Methods: A total of 111 obese children (M:F=74:37; mean age, $11.1{\pm}2.0$ yrs) were included. The children were divided into 3 groups: controls (group I, n=61), children with simple steatosis (group II, n=17), and children with non-alcoholic steatohepatitis (group III, n=33). Serum TNF-${\alpha}$ levels, homeostasis model assessment of insulin resistance (HOMA-IR), and TNF-${\alpha}$ -308 and -238 polymorphisms were evaluated. Results: There were no differences in TNF-${\alpha}$ polymorphism at the -308 or the -238 loci between group I and group II + III ($p$=0.134 and $p$=0.133). The medians of HOMA-IR were significantly different between group I and group II + III ($p$=0.001), with significant difference between group II and group III ($p$=0.007). No difference was observed in the HOMA-IR among the genotypes at the -308 locus ($p$=0.061) or the -238 locus ($p$=0.207) in obese children. Conclusion: TNF-${\alpha}$ promoter polymorphisms at the -308 and -238 loci were not significantly associated with the development of NAFLD in children; nevertheless, insulin resistance remains a likely essential factor in the pathogenesis of NAFLD in obese children, especially in the progression to NASH.