• BMB Reports
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• 제47권8호
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• pp.433-438
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• 2014

Plant sterols have shown potent anti-proliferative effects and apoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has not been investigated. In the present study, we assessed whether the stigmasterol isolated from Navicula incerta possesses apoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated the expression of pro-apoptotic gene expressions (Bax, p53) while down-regulating the anti-apoptotic genes (Bcl-2). Probably via mitochondrial apoptosis signaling pathway. With the induction of apoptosis caspase-8, 9 were activated. The DNA damage and increase in apoptotic cell numbers were observed through Hoechst staining, annexin V staining and cell cycle analysis. According to these results, we can suggest that the stigmasterol shows potent apoptosis inductive effects and has the potential to be tested as an anti-cancer therapeutic against liver cancer.

• 대한한방내과학회지
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• 제25권1호
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• pp.59-70
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• 2004

Objectives : Previous studies showed that treatment with Chungganhaeju-tang prevents hepatic inflammation and apoptosis in alcoholic liver disease. The purpose of our study is to determine if any relations exsists between the transcription factor $NF{\kappa}B$, an orchestrating expression of a large number of genes and inhibitory effects of Chungganhaeju-tang on ethanol induced apoptosis. Materials and Methods : To assess the role of $NF{\kappa}B$, we blocked NFkB activation by delivering to the kupffer cells $I{\kappa}B{\Delta}N$, a dominant negative $NF{\kappa}B$ inhibitor, and investigated if Chungganhaeju-tang still prevented apoptosis. Results : When $NF{\kappa}B$ activation was blocked, there was no inhibitory effect of Chungganhaeju-tang on ethanol induced apoptosis of kupffer cells. Conclusion : This result suggests that Chungganhaeju-tang protects the liver from ethanol induced apoptosis by activating the $NF{\kappa}B$ that plays a key role in porotecting mechanism and reducing inflammatory cytokine gene expression.

• 대한의생명과학회지
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• 제16권4호
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• pp.239-246
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• 2010

It is suggested that ovariectomy induces body weight gain primarily in the form of adipose tissue in rodents. Since liver peroxisome proliferator-activated receptor ${\alpha}$ (PPAR${\alpha}$) and uncoupling 2 (UCP2) are involved in the regulation of energy expenditure, it was investigated whether swim training regulates ovariectomy-induced adiposity and steatosis through liver PPAR${\alpha}$ and UCP2 activation in female ovariectomized mice, an animal model of postmenopausal women. Swim-trained mice had significantly decreased adipose tissue weights compared with sedentary control mice. Histological analysis showed that hepatic lipid accumulation was inhibited by swim training. Concomitantly, swim training significantly increased mRNA levels of PPAR${\alpha}$ and its target genes responsible for peroxisomal fatty acid ${\beta}$-oxidation, such as acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase and thiolase in the liver. Moreover, swim training induced the mRNA expression of UCP2. These results suggest that swim training can effectively prevent adiposity and steatosis caused by ovariectomy, in part through activation of liver PPAR${\alpha}$ and UCP2 in female obese mice.

• Molecular & Cellular Toxicology
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• 제5권4호
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• pp.283-290
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• 2009

Differential gene expression profiling was performed in the hepatic tissue of marine medaka fish (Oryzias javanicus) after exposure to benzo[a]pyrene (BaP), a polycyclic aromatic hydrocarbon (PAH), by heterologous hybridization using a medaka cDNA microarray. Thirty-eight differentially expressed candidate genes, of which 23 were induced and 15 repressed (P<0.01), were identified and found to be associated with cell cycle, development, endocrine/reproduction, immune, metabolism, nucleic acid/protein binding, signal transduction, or non-categorized. The presumptive physiological changes induced by BaP exposure were identified after considering the biological function of each gene candidate. The results obtained in this study will allow future studies to assess the molecular mechanisms of BaP toxicity and the development of a systems biology approach to the stress biology of organic chemicals.

• BMB Reports
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• 제46권4호
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• pp.207-212
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• 2013

The main purpose of this study is to examine the effect of caffeine on lipid accumulation in human hepatoma HepG2 cells. Significant decreases in the accumulation of hepatic lipids, such as triglyceride (TG), and cholesterol were observed when HepG2 cells were treated with caffeine as indicated. Caffeine decreased the mRNA level of lipogenesis-associated genes (SREBP1c, SREBP2, FAS, SCD1, HMGR and LDLR). In contrast, mRNA level of CD36, which is responsible for lipid uptake and catabolism, was increased. Next, the effect of caffeine on AMP-activated protein kinase (AMPK) signaling pathway was examined. Phosphorylation of AMPK and acetyl-CoA carboxylase were evidently increased when the cells were treated with caffeine as indicated for 24 h. These effects were all reversed in the presence of compound C, an AMPK inhibitor. In summary, these data indicate that caffeine effectively depleted TG and cholesterol levels by inhibition of lipogenesis and stimulation of lipolysis through modulating AMPK-SREBP signaling pathways.

• 한국식품과학회지
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• 제44권6호
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• pp.653-657
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• 2012

While it is known that sulfur containing amino acids (SCAA) are very important in regulating hepatocyte growth and preventing liver-diseases, the fundamental molecular mechanisms of how they exert their hepatoprotective functions are not well known. Since it is widely understood that the hepatic concentrations of S-adenosylmethionine (SAMe) in chronic liver disease patients are severely decreased, the pathophysiological importance of SAMe and its downstream antioxidant, glutathione should be discussed in order to see a big picture of relationship between SCAA and liver diseases. Chronic SAMe deficient mice have shown spontaneous hepatocellular carcinoma development due to impaired mitochondria functions with low levels of prohibitin1 protein, and through deficiency in many genes which are known to ameliorate genetic instability, such as APEX1 and DUSP1, the functions of which are recovered by SAMe treatment. In this review, current knowledge of the basic concepts of the mechanisms through which SCAAs protect the liver will be discussed in detail. Also, a possible tumor suppressor in livers, prohibitin1, and its functional relationship with SAMe will be discussed.

• Molecules and Cells
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• 제46권7호
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• pp.399-413
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• 2023

cAMP responsive element-binding protein (CREB) is one of the most intensively studied phosphorylation-dependent transcription factors that provide evolutionarily conserved mechanisms of differential gene expression in vertebrates and invertebrates. Many cellular protein kinases that function downstream of distinct cell surface receptors are responsible for the activation of CREB. Upon functional dimerization of the activated CREB to cis-acting cAMP responsive elements within the promoters of target genes, it facilitates signal-dependent gene expression. From the discovery of CREB, which is ubiquitously expressed, it has been proven to be involved in a variety of cellular processes that include cell proliferation, adaptation, survival, differentiation, and physiology, through the control of target gene expression. In this review, we highlight the essential roles of CREB proteins in the nervous system, the immune system, cancer development, hepatic physiology, and cardiovascular function and further discuss a wide range of CREB-associated diseases and molecular mechanisms underlying the pathogenesis of these diseases.

• 한방재활의학과학회지
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• 제26권1호
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• pp.13-31
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• 2016

Objectives In this study, it was investigated whether Gami-Handayeolso-Tang (HDYST) medication has anti-obesity effects in high fat diet (HFD)-fed obese mice. Methods The experimental animals were divided into five groups-normal diet-fed (ND), high fat diet-fed control (HFD), HFD+HDYST 150, HFD+HDYST 300, and HFD+orlistat as a positive drug. The obese markers such as body weight, diet efficiency ratio, serum levels of total cholesterol, triglyceride, lipid contents, leptin, adiponectin, and GOT/GPT were measured. Also, white adipose tissue, liver weight, abdominal fat mass, hepatic lipid contents, and mRNA expression of obese-associating genes were examined in obese mice. Results In high fat diet-fed mice, HDYST administration significantly decreased body weight, diet efficiency ratio, serum levels of total cholesterol, triglyceride, LDL-cholesterol, as well as leptin and GOT/GPT, compared to the HFD group in a dose-dependent manner. HDYST increased significantly the serum levels of HDL-cholesterol and adiponectin. It also reduced the accumulation of lipids, such as total lipid and triglycerides, in organs such as liver and abdominal adipose tissue. Moreover, HDYST administration significantly decreased the expression levels of fatty acid synthetic genes, such as sterol regulatory element-binding protein-1c (SREBP-1c), FAS and Stearoyl-Coenzyme A desaturase 1 (SCD-1), in the liver tissues, while it increased the messenger RAN (mRNA) levels of fatty acid catalytic genes, such as Peroxisome proliferator activated receptor alpha (PPAR-${\alpha}$), acyl-COA oxidase (ACO), and Carnitine palmitoyltransferase-1a (CPT-1a). Conclusions Based on the results above, HDYST reveals anti-obesity effects declining body fat accumulation through the regulation of fatty acid metabolism and leptin/adiponectin serum levels. It therefore suggests that HDYST can be clinically useful for the treatment of obesity.

• Journal of Nutrition and Health
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• 제37권9호
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• pp.786-793
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• 2004

Women with menopause or rats with ovariectomy is associated with increased body weight, body fat and insulin resistance, which are components of metabolic syndrome. Increased prevalence of metabolic syndrome after menopause might be associated with mitochondrial dysfunction, since mitochondrial oxidative and phosphorylation activity is strongly correlated with insulin sensitivity. Although estradiol replacement prevents the metabolic syndrome, harmful effect of estradiol hampers the casual usage to prevent the metabolic syndrome. It has been reported that genistein has a mild estrogenic activity, decreases fat mass in mice and has an antidiabetic role in diabetic rats. Although insulin resistance is closely related to mitochondrial functions, there has not been yet any study in regard to the effect of dietary genistein on mitochondrial function in the insulin resistant female subjects induced by ovariectomy or similar situation. The present study investigated whether the supplementation of genistein in the high fat diet affected the mitochondrial function of high fat fed ovariectomized rats. Female Sprague Dawley rats (8 weeks old) were assigned to the following groups: sham-operated+ high fat diet (S, n=6); sham-operated + high fat diet with 0.1% genistein (S + G, n=7); ovariectomized + high fat diet (OVX, n=8); ovariectomized + high fat diet with 0.1% genistein (OVX+ G, n=8). Ovariectomy significantly increased body weight compared with S group. Genistein consumption in ovariectomized (OVX + G) rats decreased body weight gain compared with OVX rats. Liver weights were increased by ovariectomy. The hepatic mitochondrial protein density expressed as mg per g liver was lower in the OVX group than in the S group. However, OVX + G group showed the increased mitochondrial protein density similar to the level of S group. When mRNA levels of genes related to mitochondria such as peroxisome proliferator-activated receptor ${\gamma}$ coactivator 1 (PGC-1) and cytochrome c oxidase subunit III (COX III) were measured, there were decreases in the mRNA levels of PGC-1 and COX III in S + G, OVX and OVX + G group. The activity of cytochrome c oxidase was not different between groups. We could observe the decrease in succinate dehydrogenase (SDH) activity per g liver in OVX rats. Genistein supplement increased SDH activity. In conclusion, genistein supplementation to the OVX rats enhanced mitochondrial function by increasing mitochondrial protein density and SDH activity. The improvement in mitochondrial function by genistein can contribute to the improvement in metabolic syndrome.

• Nutrition Research and Practice
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• 제4권2호
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• pp.93-98
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• 2010

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by $CCl_4$ treatment to the control level. Hepatic injury induced by $CCl_4$ was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by $CCl_4$.