• 동아시아식생활학회지
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• 제15권5
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• pp.549-557
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• 2005

Effects of Acanthopanax senticosus extract (AS) on blood sugar content and serum lipid profiles of streptozotocin-induced diabetic rats were investigated. Experimental groups were classified into four groups, that is, normal control (NC) group, diabetic mellitus (DM) group, AS-fed group and DMAS-fed group. The AS group showed lower feed efficiency than the NC group, but the efficiency of DMAS group was higher than DM group. DMAS group showed the decreased water intake and urine by $45.5\%$ and $23.7\%$ respectively, compared with DM group. Compared with DM group, DMAS group decreased blood sugar by $46.9\%$ and triglyceride by $17.8\%$, total cholesterol by $10.0\%$ and LDL cholesterol by $22.0\%$ in serum, but increased serum HDL cholesterol by $14.4\%$ The relative percentage of liver or kidney per body weight, and the serum ALT activity in DMAS group were lower than those of DM group. There were no significant differences in hepatic glutathione(GSH) contents and total xanthine oxidase(XOD) activities among experimental groups. The hepatic lipid peroxide(LPO) content in DMAS group decreased by $54.6\%$ compared with that in DM group. The XOD (O type) and the ratio of O type to total type of both STZ-treated groups (DM and DMAS) were higher than those of NC group, but less conversion of D to O type was observed in DMAS group than in DM group. There was no significant difference in GST activity between NC and AS, but STZ-treated groups showed lower glutathione S-transferase(GST) activity than NC. In conclusion, it seems that AS reduces blood sugar by inhibiting the activity of xanthine oxidase type O as an oxygen-free radical generating system which induces the tissue damage. Antidiabetic effect of AS may regulate diabetes-induced high lipid profiles in blood.

• Preventive Nutrition and Food Science
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• 제8권4호
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• pp.377-382
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• 2003

This study investigated the effects of green tea on the muscle antioxidative defense system in the white & red gastrocnemius muscles of rats after aerobic exercise. Male Sprague-Dawley rats weighing 150 10 g were randomly assigned to a control group, non-exercise with green tea group (G group), and exercise training group. The exercise training group was then further classified as the training (T) group and training with green tea (TG) group, the latter of which was supplemented with green tea in the drinking water during the experimental period. The rats in the exercise training groups (T and TG) were subjected to aerobic exercise on a treadmill 30 min/day at a speed of 28 m/min (7% incline) 5 days/week, while the other groups (control and G group) were cage confined for 4 weeks. Thereafter, the rats were sacrificed with an injected overdose of pentobarbital just after running. In the white muscle, the xanthine oxidase (XOD) activities were 71 % higher in the T group compared to control group, whereas the TG group had the same activity as the control group. The XOD activities in the red gastrocnemius muscle exhibited the same tendency as in the white muscle. The superoxide dismutase (SOD) activity in the white muscle was lower in the T group compared with the control group, yet significantly higher in the TG group compared with the T group. The SOD activities in the red gastrocnemius muscle exhibited the same tendency as in the white gastrocnemius muscle. The glutathione peroxidase (GSHpx) activities in the white & red gastrocnemius muscles were 43 % lower in the T group compared with the control group, yet the activities in the TG group remained at control levels. The glutathione S-transferase (GST) activity in the white muscle was not significantly different among any of the three groups, but in the red gastrocnemius muscle, the TG group had the same activity as in the control group. The thiobarbituric acid reactive substance (TBARS) contents in the white & red gastrocnemius muscles were higher in the T group than in the control but the control and TG groups had the same concentrations of TBARS. In conclusion, the supplementation of green tea in rats subjected to aerobic exercise was found to reduce the peroxidation of muscle lipids by enhancing the antioxidative defense mechanism.

• 한국식품영양과학회지
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• 제38권2호
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• pp.154-159
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• 2009

알코올에 의해 유도된 간 손상에 대한 지구자 추출물의 보호효과를 연구하였다. HepG2/2E1 세포에서 알코올로 유도된 ROS 생성과 산화적 손상에 대한 지구자 추출물 보호효과를 확인하였다. C57BL/6마우스를 대조군(NC), 알코올군(ET), 알코올과 지구자 추출물 1 g/kg body weight 투여군(ET-HD)으로 나누었다. 5 g/kg body weight의 알코올을 1주일간 ET와 ET-HD군에 투여하였다. 알코올 투여는 혈청 alanine amintransferase(ALT), aspartate aminotransferase(AST) 및 alkaline phosphatase(ALP)를 증가시키고, 지구자 추출물은 이러한 간 기능 지표효소의 증가를 억제시켰다. 간조직의 항산화 효소 활성은 알코올 투여에 의해 감소되었고, ET-HD군에서 SOD 및 GST 활성은 ET군과 비교하여 통계적으로 유의하게 높아졌다. GSH 함량은 ET군에서 NC군에 비하여 유의적으로 낮아졌고, ET-HD군에서 ET군과 비교하여 통계적으로 유의하게 높아졌으며, NC군과 유사한 함량을 나타내어 간 보호 효과를 확인할 수 있었다. 지질과산화물 함량은 ET-HD군과 NC군이 유사한 함량을 나타냄으로써 알코올에 의해 유도된 지질과산화물 증가에 의한 간손상으로부터 지구자 추출물의 보호 효과를 보여 주었다. 이상의 결과로부터, 지구자 추출물은 세포 및 동물 모델에서 알코올로 유도된 간 손상으로부터 항산화 방어 대사의 증가와 지질과산화율의 감소에 의해 간세포 보호 활성을 나타냄을 확인하였다. 이에 지구자 추출물은 알코올성 간 손상으로부터 보호 효과를 갖는 소재로 활용될 수 있을 것으로 사료된다.

• Journal of Ginseng Research
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• 제47권1호
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• pp.106-116
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• 2023

Background: Pirarubicin (THP) is an anthracycline antibiotic used to treat various malignancies in humans. The clinical usefulness of THP is unfortunately limited by its dose-related cardiotoxicity. Ginsenoside F1 (GF1) is a metabolite formed when the ginsenosides Re and Rg1 are hydrolyzed. However, the protective effects and underlying mechanisms of GF1 on THP-induced cardiotoxicity remain unclear. Methods: We investigated the anti-apoptotic and anti-oxidative stress effects of GF1 on an in vitro model, using H9c2 cells stimulated by THP, plus trigonelline or AKT inhibitor imidazoquinoxaline (IMQ), as well as an in vivo model using THP-induced cardiotoxicity in rats. Using an enzyme-linked immunosorbent test, the levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (c-TnT), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) were determined. Nuclear factor (erythroid-derived2)-like 2 (Nrf2) and the expression of Nrf2 target genes, including heme oxygenase-1 (HO-1), glutathione-S-transferase (Gst), glutamate-cysteine ligase modifier subunit (GCLM), and expression levels of AKT/Bcl-2 signaling pathway proteins were detected using Western blot analysis. Results: THP-induced myocardial histopathological damage, electrocardiogram (ECG) abnormalities, and cardiac dysfunction were reduced in vivo by GF1. GF1 also decreased MDA, BNP, CK-MB, c-TnT, and LDH levels in the serum, while raising SOD and GSH levels. GF1 boosted Nrf2 nuclear translocation and Nrf2 target gene expression, including HO-1, Gst, and GCLM. Furthermore, GF1 regulated apoptosis by activating AKT/Bcl-2 signaling pathways. Employing Nrf2 inhibitor trigonelline and AKT inhibitor IMQ revealed that GF1 lacked antioxidant and anti-apoptotic effects. Conclusion: In conclusion, GF1 was found to alleviate THP-induced cardiotoxicity via modulating Nrf2 and AKT/Bcl-2 signaling pathways, ultimately alleviating myocardial oxidative stress and apoptosis.

• Food Science and Biotechnology
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• 제17권2호
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• pp.367-372
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• 2008

Cellular protection against carcinogens could be achieved by the induction of phase 2 detoxifying and antioxidant enzymes such as glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO1). Nuclear transcription factor E2-related factor 2 (Nrf2) binds to antioxidant response element (ARE) in the promoter region of these genes and the resulting transactivation occurs. In the present study the effect of gujeolcho (Chrysanthemum zawadskii) roots on the Nrf2-ARE pathway were investigated. C. zawadskii root extract was fractionated with a series of organic solvents and their ability to induce Nrf2-ARE pathway was examined. We separated the most potent dichloromethane (DCM) fraction into 12 sub-fractions and found several sub-fractions with strong effects on the Nrf2-ARE pathway. Fraction 4 strongly induced the ARE-reporter gene activity as well as Nrf2 expression. Sitosterol was isolated as a major compound in fraction 4 although its activity was not as potent as its mother fraction. These results indicate that C. zawadskii roots might be used as a potential natural chemopreventive source.

• 동의생리병리학회지
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• 제17권1호
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• pp.241-246
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• 2003

Bambusae Caulis in Liquamen(BCL) has been used to relieve the cough and asthma, and remove the phlegm in traditional Oriental medicine. In recent years, it was studied for its antiinflammatory, antiallergenic, immune-modulating, and anticarcinogenic capabilities. This experiment was performed to evaluate the microarray profiles of CD genes in human mast cells before and after BCL treatment. The results are as follows: The expression of 51 of the genes studied was up-regulated in the Bel-treated group; they include the genes coding L apoferritin, beta-2-microglobulin, ferritin light polypeptide, CD63, monocyte chemotactic and activating fact, heme oxygenase 1, CD140a, integrin alpha M, colony stimulating factor 2 receptor, eukaryotic translation elongation factor, CD37, interleukin 18, NADH dehydrogenase 1 beta, CD48, 5-lipoxygenase activating protein, interleukin 4, ribosomal protein L5, GABA(A) receptor-associated protein, beta-tubulin, integrin beta 1, CD162, CD32, lymphotoxin beta, alpha-tublin, integrin alpha L, CD2, CD151, CD331, 90 kDa heat shock protein, CD59, CD3Z, microsomal glutathione S-transferase 2, CD33, CD162R, cyclophilinA, CD84, interleukin 9 receptor, interleukin 11, CD117, CD39-Like 2, and so forth. The expression of 7 of the genes studied was down-regulated in the BCL-treated group; they include the genes coding con, CD238, SCF, CD160, CD231, CD24, and CD130. Consequently, the treatment of BCL on the human mast cells increased the expression of 51 genes and decreased the expression of 7 genes. These data would provide a fundamental basis to the traditional applications of Bambusae Caulis in Liquamen.

• Toxicological Research
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• 제13권1_2호
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• pp.23-27
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• 1997

This study was performed to examine the anti-cancer effect of Red Ginseng in the DENGalN-PH-induced hepatic tumor model system in rats. One hundred of male SPF Sprague-Dawley rats(6weeks old) were randomly divided into five groups. Rats in groups 1, 2, 3, and 4 were administered to diethylnitrosamine intraperitoneally 200 mg/kg body weight for the caner initiation. Rats in group 5 were given to saline as a control. On two weeks after cancer initiation, rats in groups 1 and 3 were fed on diet containing 0.01% of acethylaminofiuorene(AAF) which is strong cancer-promotor for 6 weeks, while rats in groups 2 and 4 were fed on water containing 0.05% of phenobarbital which is weak cancer.promotor for 6 weeks. Rats in groups 1 and 2 were treated with diet containing 3% of Red Ginseng for six weeks(from 9th week till 15th week after cancer initiation). Rats in all groups were necropsied time-sequencially at 8, 15, and 36 weeks. The hepatic lesions of rat treated with carcinogens expressed glutathione S-transferase placental form(GST-P) at 8 week. The GST-P positive foci of rats treated with AAF were larger than that of any other rats, while the GST-P positive foci of rats treated with AAF and red ginseng were significantly decreased. This anti-cancer effect of Red ginseng might be involved in the enhacement of natural killer cell activity. To know whether there is direct relationship between Red Ginseng and natural killer cell activity, the activity of natural killer cell was examined after treatment AAF, AAF+Red ginseng and Red ginseng only, respectively. Comparing with natural killer cell activity in AAF-treated group, natural killer cell activity was significantly activated in AAF+ Red ginseng-treated group. This indicated that Red ginseng might enhance natural killer activity after treatment carcinogen in rats. These results suggested that Red ginseng might have a cancer prevention ability by promoting natural killer cell activity during hepatocarclnogenesis.

• Molecular & Cellular Toxicology
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• 제1권3호
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• pp.164-171
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• 2005

Toxicological studies have an object of detecting adverse effects of a chemical on an organism based on observed toxicity marker (i.e., serum biochemical markers and chemical-specific gene expression) or phenotypic outcome. To date, most toxicogenomic studies concentrated on hepatic toxicity. cDNA microarray analysis enable discrimination of the responses in animals exposed to different classes of hepatotoxicants. In an effort to further characterize the mechanisms of 2, 3, 7, 8,-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin)-mediated toxicity, comprehensive temporal-responsive microarray analyses were performed on hepatic tissue from Sprague-Dawley rats treated with TCDD. Hepatic gene expression profiles were monitored using custom DNA chip containing 490 cDNA clones related with toxicology. Gene expression analysis identified 26 features which exhibited a significant change. In this study, we observed that the genes related with oxidative stress in rats exposed to Dioxin, such as CYPIIA3 and glutathione S-transferase, were up-regulated at 24hr after exposure. In this study, we carried out to discover novel evidence for previously unknown gene expression patterns related to mechanism of hepatic toxicity in rats exposed to dioxin, and to elucidate the effects of dioxin on the gene expression after exposure to dioxin.

• Toxicological Research
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• 제34권4호
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• pp.291-296
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• 2018

Chemical carcinogenesis is a multistep process. Genotoxic carcinogens, which are DNA-reactive, induce DNA adduct formation and genetic alterations in target cells, thereby generating mutated cells (initiation). Subsequently, preneoplastic lesions appear through clonal proliferation of the mutated cells and transform into tumors (promotion and progression). Many factors may influence these processes in a dose-dependent manner. Therefore, quantitative analysis plays an important role in studies on the carcinogenic threshold of genotoxic carcinogens. Herein, we present data on the relationship between key carcinogenic events and their deriving point of departure (PoD). Their PoDs were also compared to those of the carcinogenesis pathway. In an experiment, the liver of rats exposed to 2-amino-3,8-dimethylimidazo-(4,5-f)quinoxaline (MeIQx) was examined to determine the formation of MeIQx-DNA adducts, generation of mutations at LacI transgene, and induction of preneoplastic glutathione S-transferase placental form (GST-P)-positive foci and tumors (benign and malignant). The PoDs of the above key events in the carcinogenicity of MeIQx were increased as the carcinogenesis advanced; however, these PoDs were lower than those of tumor induction. Thus, the order of key events during tumor induction in the liver was as follows: formation of DNA adducts ${\ll}$ Mutations ${\ll}$ GST-positive foci (preneoplasia) ${\ll}$ Tumor (adenoma and carcinoma). We also obtained similar data on the genotoxic and carcinogenic PoDs of other hepatocarcinogens, such as 2-amino-3,8-dimethylimidazo(4,5-f)quinoline. These results contribute to elucidating the existence of a genotoxic and carcinogenic threshold.

• 한국환경성돌연변이발암원학회지
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• 제16권2호
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• pp.109-116
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• 1996

To study the effect of dietary $\omega 6/\omega 3$ fatty acid ratios on the preneoplastic lesions and lipid peroxidation in rat hepatocellular chemical carcinogenesis, placental glutathione S-transferase(GST-P) positive foci area and numbers, glucose 6-phosphatase(G6Pase) activity, thiobarbituric acid reactive substances (TBARS) were measured. Male Sprague-Dawley rats were fed 5 different diets-low $\omega 6/\omega 3$ ratio with fish oil (Low-F), low $\omega 6/\omega 3$ ratio with perilia oil(Low-P), moderate ratio with perilia oil(Moderate), blend of 10 different commercial fats and oils(High-BL) and high $\omega 6/\omega 3$ ratio(High)-for 8 weeks. Hepatocarcinogenesis was induced by modified Ito model. The area of GST-P positive loci was the lowest in Moderate group and in ascending order of Low-F < Low-P < High-BL < High. But statistically, only Moderate and High groups were significantly different. The number of GST-P positive foci showed the same trend as foci area. The activities of G6Pase, membrane stability marker, were increased as $\omega 6/\omega 3$ ratio decreased. Lipid peroxidation values (TBARS) were the lowest in Low-F group and it is significantly different from Moderate, High-BL and High groups. When dietary $\omega 6/\omega 3$ ratio was moderate(4.06), hepatocarcinogenesis was suppressed compared with high or low $\omega 6/\omega 3$ ratios. Blend fat, commonly consumed among Koreans, did not show any suppressive effect on carcinogenesis because of high ratio(6.7). These results suggest that dietary $\omega 6/\omega 3$ ratio influences hepatocellular chemical carcinogenesis. It is recommended that appropriate $\omega 6/\omega 3$ ratio should be around 4.0. and we recommend to use more $\omega 3$ fatty acid in food preparation to reduce the risk of hepatocarcinogenesis.