• Nutritional Sciences
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• 제7권2호
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• pp.76-82
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• 2004

Pine needles are known as a traditional medicine and their ingestion has been shown to be beneficial to human beings. Following induction of the neoplastic process in rats by azoxymethane (AOM), we determined the effects of pine needle supplementation on colon carcinogenesis and on antioxidant systems in the blood and liver. Five week old male Fisher 344 rats were injected with AOM (15 mg/kg) once a week for two weeks. After the second injection, 18 rats were randomly assigned into two groups and were fed a casein-based high-fat diet (120 g fat and 1 g cholesterol/kg diet) with or without pine needle powder (10%w/w). After 6 weeks, rats receiving pine needle powder showed a 40% lower incidence of the number of colonic preneoplastic lesions (aberrant crypts) and a 52% lower incidence of aberrant crypt foci (p<0.01). A significantly elevated level of erythrocyte catalase activity was observed in the pine needle supplemented group (17.4$\pm$1.1 vs. 24.5$\pm$1.5, p<0.01). Pine needle supplementation also increased liver glutathione peroxidase activity (7.5$\pm$0.6 vs. 14.6$\pm$0.6, p<0.01). Other antioxidant parameters such as erythrocyte glutathione peroxidase, liver catalase activity, and plasma total antioxidant potential (TRAP), showed no statistical differences between the two groups. Our data demonstrate that pine needle supplementation improves the antioxidant system and suppresses the formation of colonic preneoplastic lesions in AOM-treated rats. This result provides additional insights into the chemo-preventative properties of pine needles.

• Asian Pacific Journal of Cancer Prevention
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• 제16권7호
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• pp.2679-2683
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• 2015

Background: Phenethyl isothiocyanate (PEITC), the most comprehensively studied aromatic isothiocyanate, has been shown to act as an anti-cancer agent mainly through modulation of biotransformation enzymes responsible for metabolizing carcinogens in the human body. Humans are often exposed to carcinogenic factors, some of which through the diet, such as polycyclic aromatic hydrocarbon benzo[a]pyrene via the consumption of over-cooked meats. Inhibition of the enzymes responsible for the bioactivation of this carcinogen, for example CYP1A1, the major enzyme required for polycyclic aromatic hydrocarbons (PAHs) bioactivation, is recognized as a chemoprevention strategy. Objective: To evaluate the inhibitory effects of PEITC against benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA and apoprotein levels. Materials and Methods: Precision cut rat liver slices were treated with benzo[a]pyrene at 1 and $5{\mu}M$ in the presence of PEITC ($1-25{\mu}M$) for 24 hours, followed by determination of CYP1A1 mRNA and apoprotein levels using quantitative polymerase chain reaction and immunoblotting. Results: Findings revealed that PEITC inhibited benzo[a]pyrene-induced rise in rat liver CYP1A1 mRNA in a dose-dependent manner as well as the apoprotein levels of CYP1A. Conclusions: It was demonstrated that PEITC can directly inhibit the bioactivation of benzo[a]pyrene, indicating chemopreventive potential.

• Toxicological Research
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• 제26권1호
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• pp.29-35
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• 2010

The present study was conducted to investigate the antimutagenic potential of the methanolic extract from the leaves of sweet potato (Ipomea batatas, IB) with the SOS chromotest (umu test) and Salmonella typhimurium TA 98 and TA 100. The anticarcinogenic effects were also studied by calculation of the $IC_{50}$ on human cancer cell lines and investigating the function of gap junction in rat liver epithelial cells. The IB extract inhibited dose-dependently the ${\beta}$-galactosidase activity induced spontaneously at concentration of more than 200 mg/ml in S. typhimurium TA 1535/pSK 1002, and decreased significantly (p < 0.01) the ${\beta}$-galactosidase activities induced by mutagen 6-chloro-9-[3-(2-chloroethylamino)proylamino]-2-methoxyacridine dihydrochloride (ICR) at dose of more than 0.4 mg/0.1 ml. The IB extract showed no effect on the spontaneous reversions of S. typhimurium TA 98 and 100 but benzo(${\alpha}$)pyrene (BaP)-stimulated reversions were decreased dose-dependently (p < 0.01) at the concentration of more than 100 mg/ml. The $IC_{50}$ value of stomach cancer cells was lower than that of normal rat liver epithelial cells, but the values of colon and uterine cancer cell lines were similar to those of normal rat liver epithelial cells. The transfer of dye through gap junctions was not affected by treatment of the IB extracts at any concentration during treatment periods. The simultaneously treatment of IB extract and 12-O-tetradecanoylphorbol-13-acetate (TPA) effectively prevented the inhibition of dye transfer induced by TPA 1 hour after treatment at all exposed concentrations. The number of gap junctions was significantly (p < 0.01) increased by the treatment with IB extract at concentrations of more than 40 ${\mu}g$/ml. The inhibition of the expression of gap junction proteins by TPA (0.01 ${\mu}g$/ml) was recovered dose dependently by the simultaneous treatment of IB extracts. Our data suggest that Ipomea batatas has antimutagenic and anticarcionogenic activity in vitro.

• 한국축산식품학회지
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• 제34권4호
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• pp.434-447
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• 2014

Though the edible bovine by-products are widely used for human consumption in most countries worldwide but the scientific information regarding the nutritional quality of these by-products is scarce. In the present study, the basic information regarding the yields, physicochemical and nutritional compositions of edible Hanwoo bovine by-products was studied. Our results showed that the yields, physicochemical and nutritional composition widely varied between the by-products examined. The highest pH values were found in rumen, reticulum, omasum and reproductive organ. Heart, liver, kidney and spleen had the lowest CIE $L^*$ values and highest CIE $a^*$ values. Liver had the highest vitamin A, B2 and niacin contents whereas the highest B1 and B5 contents were found in kidney. The highest Ca content was found in rumen, reticulum, omasum, head and leg while the highest Mn and Fe contents were found in rumen, omasum and spleen, respectively. Liver had the highest Cu content. Total essential amino acids (EAA)/amino acids (AA) ratios ranged between the by-products from 38.37% to 47.41%. Total polyunsaturated fatty acids (PUFA) levels ranged between the by-products from 2.26% to 26.47%, and most by-products showed favorable PUFA/SFA ratios. It is concluded that most of by-products examined are good sources of essential nutrients and these data will be of great importance for promotion of consumption and utilization of beef by-products in future.

• Asian Pacific Journal of Cancer Prevention
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• 제17권3호
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• pp.993-1001
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• 2016

Type 2 diabetes mellitus patients are at increased risk of many forms of malignancies, especially of the pancreas, colon and hepatocellular cancer. Unfortunately, little is known of the possible interaction between antidiabetic drugs and anticancer agents. The present study investigates the influence of metformin (MET) and sitagliptin (SITA) on the in vitro anticancer activity of the microtubule depolymerization inhibitor agent epothilone A (EpoA). Hepatocellular liver carcinoma cell line (HepG2) viability and apoptosis were determined by the MTT test and by double staining with PO-PRO-1 and 7-aminoactinomycin D, respectively, after treatment with EpoA, metformin or sitagliptin. The levels of nuclear factor NF-${\kappa}B$ and p53 were evaluated in the presence and absence of inhibitors. While EpoA and MET inhibited HepG2 cell proliferation, SITA did not. EpoA and SITA induced higher p53 levels than MET. All tested drugs increased the level of NF-${\kappa}B$. Only MET enhanced the proapoptotic effect of EpoA. The EpoA+MET combination evoked the highest cytotoxic effect on HepG2 cells and led to apoptosis independent of p53, decreasing the level of NF-${\kappa}B$. These findings support the link between NF-${\kappa}B$ and p53 in the modulation of apoptotic effects in HepG2 cells treated by EpoA. Our studies indicate that the combination of EpoA and MET applied in subtoxic doses has a stronger cytotoxic effect on liver cancer cells than each of the compounds alone. The therapeutic advantages of the combination of EpoA with MET may be valuable in the treatment of patients with diabetes mellitus type 2 (T2DM) and liver cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권17호
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• pp.7149-7152
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• 2014

A large number of epidemiological studies have demonstrated that obesity is a risk factor for several human cancers. Several animal studies using rodents with diet-induced or genetic obesity have also demonstrated that obesity can promote tumor development. However, the effects of obesity on the early stages of carcinogenesis, and especially on the spontaneous occurrence of somatic gene mutations, remain unclear. To investigate the effects of obesity on the rate of spontaneous gene mutations, we performed reporter gene mutation assays in liver, kidney, and colon, organs in which obesity appears to be associated with cancer development on the basis of epidemiological or animal studies, in mice with high fat diet (HFD)-induced obesity. Six-week-old male and female C57BL/6 gpt delta mice were fed HFD or standard diet (STD) for 13 or 26 weeks. At the end of the experiments, reporter gene mutation assays of liver, kidney, and colon were performed. Final body weights and serum leptin levels of male and female mice fed HFD for 13 or 26 weeks were significantly increased compared with corresponding STD-fed groups. Reporter gene mutation assays of liver, kidney, and colon revealed that there were no significant differences in gpt or $Spi^-$ mutant frequencies between STD- and HFD-fed mice in either the 13-week or 26-week groups. These results indicate that HFD treatment and consequent obesity does not appear to influence the spontaneous occurrence of somatic gene mutations.

• 대한한방내과학회지
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• 제29권3호
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• pp.703-715
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• 2008

This experiments was performed to determine the effects of Gangzitongmaekeum(降脂通脈飮 : GTE) on antioxidation activity and hyperlipidemia induced by hypercholesterolemic diet in mice. The results obtained were as follows : 1. GTE showed a safety in cytotoxicity and toxicity of human fibroblast cells and liver. 2. GTE showed DPPH scavenging activity, superoxide dismutase (SOD)-like activity and inhibitory effect on reactive oxygen species (ROS). 3. GTE treated mice showed body and liver weight decrease, compared to the hyperlipidemia-induced control group. 4. GTE decreased total cholesterol and LDL cholesterol levels significantly, but HDL cholesterol levels not significantly. 5. GTE decreased triglyceride levels significantly. 6. Glucose levels in GTE treated mice significantly decreased compared to the hyperlipidemia-induced control group. 7. Albumin levels in GTE treated mice were similar with the hyperlipidemia-induced control group. 8. The lipophagy in liver compared with the control group tended to be decreased in GTE treated mice. In the change of aorta, the cell was regular and boundary of vessel wall was clear, compared to the hyperlipidemia-induced control group. 9. TBARS levels in GTE treated mice significantly decreased compared to the hyperlipidemia-induced control group. 10. The change of SOD and catalase activity significantly increased compared to the hyperlipidemia-induced control group. 11. ACAT mRNA level and HMG-CoA reductase mRNA levels in GTE treated mice significantly decreased compared to the hyperlipidemia-induced control group. Conclusion : These results suggest that Gangzitongmaekeum is effective in antioxidation activity and dietary hyperlipidemia-induced mice.

• 셀메드
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• 제2권4호
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• pp.35.1-35.11
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• 2012

The homeopathic remedy Chelidonium majus 200C (Chel-200) is traditionally used by homeopathic practitioners in liver ailments arising out of hepatotoxicity. The present investigation was aimed at examining whether vitamin C (L-ascorbic acid or AA), used in both traditional and orthodox medicines, can show better effects when used in combination with Chel-200, in favorably modifying the toxicological effects induced by the chronic feeding of p-dimethylaminoazobenzene (p-DAB, initiator) and phenobarbital (PB, promoter) in mice for 7 days through 120 days to induce hepatotoxicity and liver tumors. Mice were euthanized at 7, 15, 30, 60, 90, and 120 days of carcinogen feeding to assess various cytogenetical, biochemical and histological changes occurring in them. In a placebo controlled study, Chel-200 or the respective placebo (Alcohol-200C or Alc, "vehicle" of homeopathic drug), was orally administered to toxicant-fed mice. Sub-groups of the mice receiving Chel-200 were also fed either AA or an Alc placebo and their individual and conjoint effects were studied against the respective controls, to evaluate if the combination therapy of Chel-200 with AA can be of additional help in the amelioration of the toxicities generated by the toxicants. The combined feeding of Chel-200 and AA appeared to reduce the cytotoxic and genotoxic effects significantly, when compared to either only the Chel-200 or AA fed group. A similar trend was also obtained in the results of scanning and transmission electron microscopic studies of the livers. Experiments in other mammalian models are warranted to confirm if these drugs in combination could be used in palliative care of human patients with liver diseases including cancer.

• 대한한의학회지
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• 제32권1호
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• pp.109-120
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• 2011

Objectives: The aim of this investigation was to evaluate the efficacy of KHchunggan-tang aqueous extract on the experimental nonalcoholic fatty liver disease(NAFLD) induced by palmitate. Materials and Methods: To generate a cellular model of NAFLD, we used HepG2 cells, a human hepatoma cell line, treated with 0.5 mM palmitate. By this cellular model, effects of KHchunggan-tang aqueous extract were evaluated. Intracellular lipid accumulation, free radical formation, and apoptosis were detected by Nile red staining, 2',7'-dichloroflourescin diacetate(H2DCF-DA), and 4',6-diamidino-2-phenylindole(DAPI)/propidium iodide(PI) staining, respectively. Some proteins related with NAFLD were determined by western blot. Results: Typical pathological features of NAFLD occurred in the cellular model. Palmitate increased the levels of intracellular lipid vacuoles, decreased cell viability, and increased apoptosis. Palmitate increased free radical formation and lipid peroxidation, too. However, KHchunggan-tang aqueous extract reduced palmitate-induced pathologic features, i.e. steatosis, free radical formation, and apoptosis. In addition, KHchunggan-tang aqueous extract suppressed palmitate-activated c-Jun N-terminal kinase(JNK) signaling, and SP600125, a JNK inhibitor, significantly reversed the palmitate-induced pathologic changes as KHchunggan-tang aqueous extract. It means that the signaling pathway other than JNK can be involved in the KHchunggan-tang mediated cellular protection of palmitate-treated Hep G2 cells. Conclusions: These results suggest that KHchunggan-tang aqueous extract has hepatoprotective effects on NAFLD with combined properties in cellular steatosis, ROS production, and cytoprotection, and thus may have valuable clinical applications for treatment of this chronic liver disease.

• 대한한의학방제학회지
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• 제17권2호
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• pp.163-174
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• 2009

Reactive oxygen species(ROS) can induce hepatotoxicity and trigger apoptosis in the liver. In this study, we investigated the sulfated polysaccharide A-1 from Opuntia ficus-indica against alcoholic oxidative stress in human liver Hep G2 cell. An antioxidant substance A-1 obtained from the enzymatic extract of Opuntia ficus-indica fruit was purified by DEAE-cellulose ion exchange and sephadex G-100 gel permeation chromatography. The purification yield and molecular weight were 14.3% and 1.8 KDa, respectively. The A-1 predominately contained arabinose, galactose, rhamnose and also sulfate group. The structure of A-1 was investigated by periodate oxidation, FT-IR spectroscopy, $^1H$-NMR spectroscopy. The A-1 mainly composed of alternating unit of ${\rightarrow}4$)-$\alpha$-L- Rapp-2-$SO_3^-$-$\alpha$-L-Galp-($1{\rightarrow}$ and branched linkage of $\beta$-D-Arbp- ($5{\rightarrow}$. The antioxidative activity was measured using the SOD, CAT activity and GSH assay, respectively. The expression of Nrf2 protein was analyzed by western blotting. The viable cell count analyzed by autofluorescence. Oxidative stress induced by ethanol(1 M) were dramatically reduced by A-1 treatment. A-1 also prevented cell death induced by oxidative stress. It also increased expression Nrf2 protein level. We concluded that sulfated polysaccharide A-1 from Opuntia ficus-indica effectively protect Hep G2 liver cell from alcoholic oxidative stress.