• 대한한의학회지
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• 제32권1호
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• pp.164-174
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• 2011

Objective: The antiplatelet agent aspirin has been widely used for treating atherosclerosis in western medicine, and its efficacy has been proven in cardiac and extracardiac vascular diseases. On the other hand, Hyeolbuchukeo-tang has been widely used for treating blood stasis syndrome in traditional medicine. Therefore we investigated whether Hyeolbuchukeo-tang could have a synergic effect along with aspirin. Methods & Materials: Male $ApoE^{(-/-)}$ mice were randomly divided into three different experimental groups: a non-treated group(Control group), an aspirin-treated group(AP group), and an aspirin with Hyeolbuchukeo-tang-treated group(APH group). The control group was fed only an atherogenic diet, the AP group an atherogenic diet plus Aspirin 5 mg/kg, and the APH group an atherogenic diet plus Aspirin 5 mg/kg with Hyeolbuchukeo-tang 100 mg/kg. We investigated plasma lipid with liver function test, and performed the histological investigation of liver and abdominal aorta. Results: 1. We investigated photomicrographic changes of liver and abdominal aorta tissue. They showed that histological injury of aorta and lipid accumulations of the liver were lower in the AP and APH groups than in the control group. 2. In the APH group, plasma triglyceride levels were significantly lower than those in the control and AP groups. 3. There were no differences in aspartate aminotransferase and alanine aminotransferase levels among the control, AP and APH groups. Conclusion: The above results show that a combined treatment of Hyeolbuchukeo-tang and aspirin has a somewhat synergic effect in terms of inhibiting vessel injury and decreasing lipid deposits on liver cells without liver toxicity.

• Archives of Pharmacal Research
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• 제23권1호
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• pp.22-25
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• 2000

Formation of glutathione (GSH) conjugates with 2- or 6-(1-hydroxymethyl)- and 2-(1-hydroxyethyl)-DMNQ derivatives (DMNQ, 5,8-dimethoxy-1,4-naphthoquone was carried out in phosphate buffer (pH 7.4), in the presence of glutathione-S-transferase (GST), in rat liver S-9 fraction and by perfusion, and the rates of conjugates formation were compared and correlated to cytotoxicity. The GSH conjugates of 6-(1-hydroxyalkyl)-DMNQ derivatives were formed faster than 2-(1-hydroxyalkyl)-DMNQ derivatives under all of the media, implying that steric hindrance was the cause of lowering the rate of conjugate formation of 2-substituted derivatives. For both isomers, addition of GST did not improve the reaction rate, compared with that in buffer, while the reaction in the S-9 fraction and the perfusate was accelerated to a great extent. The catalytic effect of the S-9 fraction and the perfusate contain an effective system relaxing the steric hindrance of 2-(1-hydroxyalkyl)-DMNQ derivatives. Furthermore, a good correlation between the formation of the GSH conjugates and the cytotoxic activity of both naphthazarin isomers suggests that the steric hindrance is a cause of lowering the cytotoxicity of 2-isomers.

• Journal of Ginseng Research
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• 제44권3호
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• pp.519-526
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• 2020

Background: Bisphenol A (BPA), known as an endocrine disruptor, is widely used in the world. BPA is reported to cause inflammation-related diseases. Korean Red Ginseng (KRG) has been used safely in human for a long time for the treatment of diverse diseases. KRG has been reported of its mitigating effect on menopausal symptoms and suppress adipose inflammation. Here, we investigate the protective effect of orally administered KRG on the impacts of BPA in the liver and uterus of menopausal mice model. Methods: The transcriptome analysis for the effects of BPA on mice liver was evaluated by Gene Expression Omnibus (GEO) database-based data (GSE26728). In vivo assay to evaluate the protective effect of KRG on BPA impact in ovariectomized (OVX) mice were designed and analyzed by RNA sequencing. Results: We first demonstrated that BPA induced 12 kinds of gene set in the liver of normal mice. The administration of BPA and KRG did not change body, liver, and uterine weight in OVX mice. KRG downregulated BPA-induced inflammatory response and chemotaxis-related gene expression. Several gene set enrichment analysis (GSEA)-derived inflammatory response genes increased by BPA were inhibited by KRG in OVX mice. Conclusion: Our data suggest that BPA has commonly influenced inflammatory response effects on both normal and OVX mice. KRG protects against BPA impact of inflammatory response and chemotaxis in OVX mouse models. Our comparative analysis will provide new insight into the efficacy of KRG on endocrine disrupting chemicals and OVX mouse.

• Biomolecules & Therapeutics
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• 제24권1호
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• pp.40-48
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• 2016

The pregnane X receptor (PXR), a liver and intestine specific receptor,, has been reported to be related with the repression of inflammation as well as activation of cytochromosome P450 3A (CYP3A) expression. We examined the effect of PXR on tetrachloromethane (CCl4)-induced mouse liver inflammation in this work. Ginkgolide A, one main component of Ginkgo biloba extracts (GBE), activated PXR and enhanced PXR expression level, displayed both significant therapeutic effect and preventive effect against $CCl_4$-induced mouse hepatitis. siRNA-mediated decrease of PXR expression significantly reduced the efficacy of Ginkgolide A in treating $CCl_4$-induced inflammation in mice. Flavonoids, another important components of GBE, were shown anti-inflammatory effect in a different way from Ginkgolide A which might be independent on PXR because flavonoids significantly inhibited CYP3A11 activities in mice. The results indicated that anti-inflammatory effect of PXR might be mediated by enhancing transcription level of $I{\kappa}B{\alpha}$ through binding of $I{\kappa}B{\alpha}$. Inhibition of NF-${\kappa}B$ activity by NF-${\kappa}B$-specific suppressor $I{\kappa}B{\alpha}$ is one of the potential mechanisms of Ginkgolide A against CCl4-induced liver inflammation.

• Journal of Nutrition and Health
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• 제2권1호
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• pp.19-27
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• 1969

(1) Control values of the hepatic lipids of mouse analysed by means of thin-layer chromatography were as follows: Total cholesterol $5.23{\pm}0.46\;mg/g$ Free cholesterol $4.29{\pm}1.23\;mg/g$ Esterified cholesterol $0.94{\pm}0.30\;mg/g$ Triglycerides $15.56{\pm}1.84\;mg/g$ Free fatty acids $1.26{\pm}0.56\;mg/g$ Phospholipids $29.84{\pm}6.11\;mg/g$ Total lipids $62.44{\pm}12.13\;mg/g$ (2) The garlic administration brought significant elevations in the hepatic contents of free and esterified cholesterds, triglycerides, free fatty acids, and phospholipids in the mouse, when it was injected in excess (2%, 10% suspension) intraperitoneally. (3) The total hepatic lipids of mouse were increased in corelation with the amount of the garlic administered to the animals. (4) A brief discussion was made on the results obtained.

• Molecular & Cellular Toxicology
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• 제3권3호
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• pp.172-176
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• 2007

Butylated hydroxytoluene (BHT) is widely used antioxidant food additives. It has been extensively studied for potential toxicities. BHT appears adverse effects in liver and thyroid. In this study, we evaluated the genetic toxicity of BHT with more advanced methods, in vitro mouse lymphoma assay $tk^{+/-}$ gene assay (MLA) and in vivo mouse supravital micronucleus (MN) assay. BHT did not appear the significantly results in the absence and presence of metabolic activation system with MLA. Also, in vivo testing of BHT yielded negative results with supravital MN assay. These results suggest that BHT itself was not generally considered genotoxic.

• Molecular & Cellular Toxicology
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• 제3권2호
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• pp.113-118
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• 2007

Chlorobenzenes due to their acute toxicity and the capability of bioaccumulating are of great health and environmental concern. Especially, 1, 2-dichlorobenzene (CAS No. 95-50-1) is used for organic synthesis, dye manufacture, as a solvent and for other applications in chemical industry. Adverse effects of 1, 2-dichlorobenzene includes increases in liver and kidney weights and hepatotoxicity. In this study, we evaluated the genetic toxicity of 1, 2-dichlorobenzene with more advanced methods, in vitro mouse lymphoma assay $tk^{+/-}$ gene assay (MLA) and in vitro mouse supravital micronucleus (MN) assay. 1, 2-Dichlorobenzene appeared the significantly positive results and the induction of large mutant colonies only in the presence of metabolic activation system with MLA. But in vitro testing of 1, 2-dichlorobenzene yielded negative results with supravital MN assay. These results suggest that 1, 2-dichlorobenzene may play a mutagen rather than clastogen in vitro mammalian system.

• 대한한방내과학회지
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• 제32권4호
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• pp.487-496
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• 2011

Objectives : The aim of this study was to investigate the hepatoprotective effect of Soshiho-tang (SSH) in mouse primary liver cells against hydrogen peroxide ($H_2O_2$)-induced oxidative stress. We also elucidated the molecular mechanism of hepatoprotective effect by SSH. Methods : Cell viability, level of ALT, AST and LDH, intracellular ROS level, mRNA expression and activity of antioxidant enzymes were used to evaluate hepatoprotection of SSH against $H_2O_2$. Target gene expressions were analyzed by real-time PCR. Results : Pre-treatment with SSH for 1 hour prevented cytotoxicity against $H_2O_2$. $H_2O_2$-induced ROS level decreased under SSH pre-treatment. mRNA expression of GPx and SOD increased in SSH-treated cells. In addition, HSP72 and HSP40 gene expression were elevated under SSH-treatment. Conclusions : These results indicate that SSH protects mouse primary liver cells from $H_2O_2$-induced oxidative injury. This hepatoprotective activity of SSH is mediated by decreasing intracellular ROS and increasing antioxidant enzyme expression (GPx and SOD) and stress response protein (HSP72 and HSP40).

• 한국환경성돌연변이발암원학회지
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• 제23권1호
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• pp.30-34
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• 2003

Recent industrial society has human widely exposed to PAHs (polynuclear aromatic hydrocarbons) that are comming from the incomplete combustion of organic material as wider spread environmental contaminants. Biological activities of PAHs are not known although PAHs are considered as carcinogens. Our laboratory have been studied the effect of PAHs in the mouse liver hepa 1 cells. In this study, we examined the mouse liver hepa-l cells as a new bioassay system to evaluate bioactivity of PAHs. We have selected 13 PAHs to examine bioassay using cyp1a1-luciferase reporter gene expression system where cyp1a1 1.6 Kb 5flanking region DNA was cloned in front of luciferase reporter gene and this plasmid was transfected into hepa 1 cells transiently. This cells then used for the study to observe the effect of PAHs. We demonstrated that PAHs induced the CYP1A1 promoter and 7-ethoxyresolufin O-deethylase (EROD) activities in a concentration-dependant manner. Some of PAHs showed stronger stimulatory effect on CYP1 gene expression than TCDD. Acenaphthene, anthracene, fluorine, naphthalene, pyrene, phenanthrene, carbazole were weak responders to cyp1a1 promoter activity stimulation and EROD induction in hepa 1 cells and these chemicals seemed to respond less to EROD than cyp1a1 promoter activity. Benz(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, chrysene, and dibenzo(a,h)anthracene showed strong response to cyp1a1 promoter activity stimulation and also EROD induction in hepa 1cells. Results of dose response study suggested that four strong responding PAHs, such as benzo(a)anthracene benzo(k)fluoranthene, chrysene, and dibenzo(a, h)anthracene might be mediated through arylhydrocarbon receptor system in hepa1 cells.

• 대한의생명과학회지
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• 제8권3호
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• pp.179-184
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• 2002

We investigated the morphological changes and TUNEL reaction of apoptotic cells in the liver of D-galactosamine (20 mg/mouse) and lipopolysaccharide (5 $\mu\textrm{g}$/mouse)-treated 30 mice (BALB/c), and in additioa also of apoptotic cells in kidney and spleen. The livers and other some organs of mice at 6, 12, 24, 48 and 72 hrs after treatment were collected and were fixed with 10% neutral formalin and paraffin sections were stained with hematoxylin-eosin or terminal deoxynucleotidly transferase-mediated dUTP nick end labeling (TUNEL) method. Morphological changes in apoptotic hepatocytes were chondensation of nuclei and density of cytoplasms, then the margination and pyknosis of chromatin, the formation of half-moon- or horse-shoe- or ship-like shapes of condensed chromatin mass, lastly formation of apoptotic bodies, disappearance of nuclear envelopes, decrease of stainability, then lysis and disappearance of apoptotic bodies. TUNEL positive reactions of hepatocytes were appeared first moderate in uncondensed hepatocytes, severe in condensed hepatocytes, moderate in chromatin-marginated hepatocytes. These reactions also were appeared moderate in hepatocytes with half-moon- or horse-shoe- or ship-like pyknotic chromatin mass or apoptotic bodies, and mild or negative in hepatocytes with lysed apoptotic bodies or with disappeared nuclear envelopes. Consequently these results suggested that TUNEL positive reactions of hepatocytes appeared at more early stages than appearance of chromatin condensation and disappeared at more early stage than disappearance of histological findings of apoptosis. We also confirmed that the differentiation of apoptotic cells from normal healthy cells of Kupffer cells and vascular endothelial cells in liver, reticular cells and lymphocytes in spleen and epithelial cells of tubules and ducts in kidney was impossible in H-E preparations but was possible in TUNEL preparations.