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Studies on the Anticancer Effect of Apigenin in KB Cell Xenograft Nude Mouse Model (구강암 세포주를 이종 이식한 누드마우스에서 apigenin의 경구투여에 따른 항암효능에 관한 연구)

  • Lee, Jin-Seok;Seo, Hyeong-Seok;Kim, So-Jung;Kim, Hyeong-Jin;Kim, Jin;Lee, Seung-Ho;Park, Young-Seok;Park, Byung-Kwon;Kim, Byeong-Soo;Kim, Sang-Ki;Jung, Ji-Youn
    • Journal of Life Science
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    • v.20 no.10
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    • pp.1519-1524
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    • 2010
  • Apigenin (4', 5, 7-trihydroxyflavone), a common dietary flavonoid abundantly present in fruits and vegetables, has shown remarkable anti-proliferative effects against various malignant cell lines. To observe the anti-proliferative effects, oral cavity cancer cell lines, $6{\times}10^3$ cells/well (96 well plate) of KB oral cavity tumor cells were plated and 24 hr later treated with apigenin for one day, after which MTT assay was performed. Apigenin induced cell death in a dose-dependent manner after incubation. Cell viability was significantly decreased in the group treated with 100 ${\mu}M$ apigenin for 24 hr (p<0.05) compared to the control group. To assess apoptosis, the nuclei of KB cells were stained with DAPI. The presence of chromatin condensation in the apigenin treated cells was detected on a fluorescent microscope (${\times}200$). We investigated the in vivo growth inhibitory effects of apigenin on oral cavity cancer KB tumor xenograft subcutaneously implanted in male nude mice. Apigenin was administered to mice by gavage at doses of 25 and 50 mg/kg/day in 0.2ml of PBS. Tumor volume was significantly decreased in 25 and 50 mg/kg apigenin-administration groups compared to the control group. For apoptosis analysis, TUNEL staining was performed. A significant increase in TUNEL positive cells was found in the 25 mg/kg apigenin administration group compared to the non- apigenin administration group. Histopathological changes were not observed. These results indicate that apigenin inhibits oral cavity cancer cell growth through the induction of apoptosis.

Effects of Pine Needle Extract Oil on Blood Glucose and Serum Insulin Levels in db/db Mice (2형 당뇨 마우스에서 솔잎 추출용액의 경구투여가 혈당조절에 미치는 영향)

  • Kim, Mi-Joung;Ahn, Jin-Hong;Choi, Kang-Ho;Lee, Yun-Hak;Woo, Gyeong-Jin;Hong, Eun-Kyung;Chung, Young-Shin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.3
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    • pp.321-327
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    • 2006
  • This study was performed to investigate the hypoglycemic effect of pine needle extract oil against type 2 diabetes. Six-week-old male C57BL/Ks(db/db) mice were divided into four groups : negative control, pine needle extract oil low dose, high dose and positive control groups, which fed daily for 6 weeks with corn oil, pine needle extract oil 112.5 mg/kg, 450 mg/kg or metformin (150 mg/kg ), respectively. The oral administration of the pine needle extract oil resulted in the significant and dose-dependent decreases of blood glucose levels in comparison with corn oil treatment. The levels of HbAlc showed a tendency of the decrease by the high dose treatment of the pine needle extract oil and were positively correlated with blood glucose levels (r=0.5046, p=0.0023) . However, the levels of serum insulin and C-peptide were not affected by pine needle extract oil or metformin treatments. The levels of serum leptin, which is related with the insulin sensitivity, showed a tendency of the increases by pine needle extract oil treatment and were negatively correlated to blood glucose levels (r=-0.4754, p=0.0052). In conclusion, these results suggest that the pine needle extract oil have a potential for the oral anti-hyperglycemic agent and the mode of action may be related with the improvement of the insulin sensitivity through blood leptin.

Effects of Sea Tangle (Laminaria japonica) Extract and Fucoidan Drinks on Oxygen Radicals and Their Scavenger Enzymes in Stressed Mouse (스트레스 부하 마우스의 활성산소 및 제거효소에 미치는 다시마(Laminaria japonica)와 후코이단 음료의 영향)

  • CHOI Jin-Ho;KIM Dae-Ik;PARK Soo-Hyun;KIM Dong-Woo;KIM Chang Mok;KOO Jae Geun
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.32 no.6
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    • pp.764-769
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    • 1999
  • This study was designed to investigate the effects of sea tangle (Laminaria japonica) extract (Dasi-Ex group: dry base $4.0\%$) and fucoidan-added (Fuco-I, II, III group: fucoidan of $1,0\%,\;2.0\%,\;3.0\%$ added to Dasi-Ex) drinks on the formation of oxygen radicals and scavenger enzyme activities of stressed mice. ICR male mice (20 $\pm$2 g) were fed experimental diets and these drinks instead of water for 18 days including 4 days of sociopsychological stress. Dasi-Ex and Fuco-I, II and III groups resulted in a marked decreases $20\~40\%$ in basal oxygen radical (BOR) formation, and $15\~25\%$ in induced oxygen radical (IOR) formation compared with control group. Hydroxyl radical formations were significantly inhibited about $10\%$ in Dasi-Ex group, while remarkably inhibited $30\~40\%$ in Fuco-I, II and III groups. lipid peroxide (ISO) levels in Dasi-Ex group were not significantly different from those of control group, tut Fuco-I, II and III groups resulted in a significant decreases about $10\%$ in LPO levels compared with control group, Dasi-Ex, Fuco-I, II and III groups resulted in a marked decreases ($31\%,\;36\%,\;39\%$ and $42\%$, respectively) in oxidized protein levels through production of carbonyl group. Significant differences in nitric oxide (NO) levels in Dasi-Ex group were not obtained, but NO levels were slightly inhibited about $7\%$ in Fuco-I and II groups and $20\%$ in Fuco-III group compared with control group. Significant differences in superoxide dismutase (SOD) and catalase (CAT) activities in Dasi-Ex and Fuco-I groups were not obtained, but Fuco-II and III groups resulted in a significant increases $25\~40\%$ in SOD activities, and about $10\%$ in CAT activities compared with control group. These results suggest that the sociopsychological stress and aging process could be effectively inhibited by biological activity of sea tangle and fucoidan components.

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Effects of Treadmill Exercise on Alpha-synuclein Mutation and Activated Neurotrophins in Nigrostriatal Region of MPTP-induced Parkinson Models (MPTP 파킨슨 모델의 트레드밀 운동이 알파시누크린 변성과 흑질선조체내 신경성장인자 활성화에 미치는 영향)

  • Park, Jae-Sung;Kim, Jeong-Hwan;Yoon, Sung-Jin
    • Journal of Korean Medicine Rehabilitation
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    • v.19 no.2
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    • pp.73-88
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    • 2009
  • Objectives : Neuronal changes that result from treadmill exercise for patients with Parkinson's disease(PD) have not been well documented, although some clinical and laboratory reports suggest that regular exercise may produce a neuroprotective effect and restore dopaminergic and motor functions. However, it is not clear if the improvements are due to neuronal alterations within the affected nigrostriatal region or result from a more general effect of exercise on affect areas and motivation. In this study, we demonstrate that motorized treadmill exercise improves the neuronal outcomes in rodent models of PD. Methods : We used a chronic mouse model of parkinsonism, which was induced by injecting male C57BL/6 mice with 10 doses(Every 12 hour) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (30 mg/kg) and probenecid (20 mg/kg) over 5 days. These mice were able to sustain an exercise training program on a motorized rodent treadmill at a speed of 18 m/min, $0^{\circ}$ of inclination, 40 min/day, 5 days/week for 4 weeks. At the end of exercise training, we extracted the brain and compared their neuronal and neurochemical changes with the control(saline and sedentary) mice groups. Synphilin protein is the substance that manifestly reacts with ${\alpha}$-synuclein. In this study, we used Synphilin as a manifest sign of recovery from neurodegeneration. We analyze the brain stems of the substantia nigra and striatum region using the western blotting technique. Results : There were no expression of synphilin in the saline-induced groups. The addition of MPTP(1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) greatly accelerated synphilin expression which meant an aggregation of ${\alpha}$-synuclein. But, the MPTP-induced treadmill exercise group showed significantly lower expression than the MPTP-induced sedentary group. This means treadmill exercise has a definite effect on the decrease of ${\alpha}$-synuclein aggregation. Conclusions : In this study, our results suggest that treadmill exercise promoted the removal of the aggregation of ${\alpha}$-synuclein, resulting in protection against disease development and blocks the apoptotic process in the chronic parkinsonian mice brain with severe neurodegeneration.

Effects of Persimmon (Diospyros kaki Thunb) Syrup Extracted from Persimmon and Persimmon By-products on Blood Glucose Level (감(Diospyros kaki Thunb) 또는 감부산물에서 추출한 감시럽의 혈당수치에 미치는 영향)

  • Yoo, Ki-Hwan;Kim, Seok-Jin;Jeong, Jong-Moon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.40 no.5
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    • pp.682-688
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    • 2011
  • The purpose of this study was to measure the blood glucose level and glycemic index (GI) in response to persimmon (Diospyros kaki Thunb) syrup extracted from persimmon and extract of persimmon by-products. Major component analyses of persimmon syrup I (PSI, 95:5 mixture of purified persimmon syrup and non-purified persimmon syrup) and persimmon syrup II (PSII, 50:50 mixture ratio of purified persimmon syrup and non-purified persimmon syrup) were $0.3{\pm}0.1$ and $0.6{\pm}0.2$ mg/g for total polyphenolic compounds and $70.6{\pm}0.6$ and $66.6{\pm}1.6%$ for total carbohydrates, respectively. Blood glucose responses of PSI and PSII were determined using both normal ICR mice and streptozotocin (STZ)-induced diabetic male Sprague-Dawley (SD) rats. Further, oral glucose tolerance test (OGTT) was performed on diabetic rats to assess the effects of the experimental diets. Blood glucose response and OGTT showed that blood glucose levels were significantly lower in mice and diabetic rats fed PSI and PSII compared to those fed diets of sugar, maple syrup, or honey. The GIs of healthy volunteers in response to PSI and PSII were calculated to be 51.9 and 35.7, respectively. On the contrary, the GIs of healthy volunteers fed diets including sugar, maple syrup, or honey were 52.6, 20.0, and 93.0, respectively. These results suggest that persimmon syrup can be used for both the treatment of diabetics and healthy people due to its beneficial effects on blood glucose level.

Effects of Silk Protein Hydrolysates on Blood Glucose and Serum Lipid in db/db Diabetic Mice (실크단백질 효소 가수분해물이 2형 당뇨 마우스의 혈당 및 혈청지질에 미치는 영향)

  • Shin, Mi-Jin;Park, Min-Jeong;Youn, Myung-Sub;Lee, Young-Sook;Nam, Moon-Suk;Park, In-Sun;Jeong, Yoon-Hwa
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.10
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    • pp.1343-1348
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    • 2006
  • This study was performed to investigate the effects of silk protein enzyme hydrolysates on blood glucose and serum lipid in db/db diabetic mice. Twelve week-old-male C57BL/KsJ db/db mice were divided into two groups: diabetic control group and 0.25% silk protein hydrolysates solution group, which were fed for 8 weeks. Body weight increased in the silk protein hydrolysates group compared with the diabetic control group. There were no differences in food and water intake between the diabetic control and the silk protein hydrolysates groups. The weight of liver increased in the silk protein hydrolysates group while that of kidney increased in the diabetic control group. The blood glucose level increased about 18.0% in the diabetic control group after 8 weeks while that in the silk protein hydrolysates group increased about 5.8%. Also, silk protein hydrolysates improved the glucose tolerance in C57BL/KsJ db/db mice. There was no difference in total cholesterol and non-HDL cholesterol concentration between the diabetic control and the silk protein hydrolysates group. Triglyceride concentration were lower in the silk protein hydrolysates group than in the diabetic control group (p<0.05) while HDL-cholesterol concentration were higher in the silk protein hydrolysates group than in the diabetic control group (p<0.05). This results suggest that administration of silk protein enzyme hydrolysates reduces significantly an increasing rate of 1]food glucose, decreases triglyceride, and increases HDL-cholesterol in C57BL/KsJ db/db mice.

Effect of Obesity and Diabetes on Alzheimer's APP Gene Expression in Mouse Adipose Tissues (비만 및 당뇨가 생쥐 지방조직에서의 Alzheimer's APP 유전자 발현에 미치는 영향)

  • Kim, Jin-Woo;Lee, Yong-Ho
    • Journal of Life Science
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    • v.20 no.7
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    • pp.1012-1018
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    • 2010
  • The aim of this study was to determine whether Alzheimer's amyloid precursor protein (APP) is dysregulated in adipose tissues of C57BL/6 male mice by high-fat diet (HFD) induced obesity, aging, or streptozotocin (STZ)-induced diabetes. APP mRNA expression was examined by quantitative real-time PCR (QPCR) in subcutaneous (SAT) and epididymal adipose tissues (EAT) from mice in 8 different condition groups. By combining conditions of age (16 weeks/26 weeks of age), diet (normal diet (ND)/high-fat diet), and induction of diabetes (non-diabetic/diabetic), 88 mice were divided into 8 different groups. QPCR demonstrated that APP expression in SAT was significantly increased by about two-fold in HFD-induced obese mice compared to both 16 week-old and 26 week-old mice in the ND group (16 weeks p=0.001; 26 weeks p<0.0001), but no changes in EAT was found. Particular effects of aging on APP gene expression were not observed in either adipose tissue depots. Significantly decreased APP expression was found in SAT in STZ-induced diabetic mice fed on ND or HFD at 16 weeks of age (ND p<0.05; HFD p<0.01). Linear regression analysis demonstrated that APP expression levels correlated with body weight in both the non-diabetic group (R=0.657, p<0.0001, n=39) and the diabetic group (R=0.508, p=<0.0001, n=49), but did not correlate with plasma glucose levels, which suggests that decreased APP expression in STZ-induced diabetic mice is most likely due to weight loss rather than hyperglycemia. These data confirm APP dysregulation by weight changes in humans and suggest a possible role linking midlife obesity with the later development of amyloidogenesis in the brain of older patients with Alzheimer's disease.

Amelioration of Plasma Glucose and Cholesterol levels in Db/db Mice by a Mixture of Chinese Herbs (Db/db 마우스 모델에 있어서 한약재조성물의 혈당 및 혈장 콜레스테롤 개선효과)

  • Lee, Jai-Heon;Cho, Chang-Woo;Han, Xiang-Fu;Hwang, Ji-Yeon;Kang, Min-Jung;Joo, Hee-Jeong;Kim, Mi-Eun;Seo, Yeong-Ju;Kim, Jung-In
    • Korean Journal of Medicinal Crop Science
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    • v.16 no.4
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    • pp.225-230
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    • 2008
  • Diabetes mellitus is the fifth leading cause of death among Koreans. Control of hyperglycemia and dyslipidemia is strongly correlated with decrease in risks for cardiovascular diseases, the most common and fatal diabetic complication. The effects of chronic feeding of a mixture of Chinese herbs on blood lipid profile were measured in an animal model of type 2 diabetes mellitus, db/db mice (C57BL/Ks). The Chinese herb mixture was composed of Panax ginseng C. A. Meyer,Astragalus membranaceus, Glycyrrhiza uralensis, Lycium chinense, Morus, Pueraria thunbergiana, Prunella vulgaris var. lilacina, Acanthopanax sessiliflorus, Schizandra chinensis, Scutellaria baicalensis, Dioscorea batatas, Polygonatum doratumvar. pluriflorum, Paeonia lactiflora, and Rehmannia glutinosa in a ratio of 1 : 0.7 : 0.4 : 0.7 :0.4 : 0.7 : 1.1 : 0.9 : 0.4 : 0.4 : 0.7 :0.7 : 0.9 : 0.9. Methanol extract of the Chinese herb mixture was tested for the inhibitory activity against yeast ${\alpha}$-glucosidase in vitro. The Chinese herb mixture extract inhibited ${\alpha}$-glucosidase by 25.2% at the concentration of 0.5mg/mL. Four weekold male db/db mice (n = 14) were fed AIN-93G semipurified diet or diet containing 10% powder of the Chinese herb mixture for 6 weeks after 1 week of adaptation period. Body weight (39.5 ${\pm}$ 1.6 g) and food intake (4.3 ${\pm}$ 0.6 g/day) of the Chinese herb group were not significantly different from those of the control group (40.4 ${\pm}$ 2.6 g and 4.5 ${\pm}$ 0.6 g/day). Consumption of Chinese herb mixture significantly decreased plasma glucose level (442.5 ${\pm}$ 36.0mg/dL) compared with the control group (489.8 ${\pm}$ 34.6 mg/dL, p < 0.05). Plasma cholesterol level (159.2 ${\pm}$ 18.4 mg/dL) of the Chinese herb group was significantly lower than that of the control group (185.4 ${\pm}$ 13.7 mg/dL, p < 0.05). Blood glycated hemoglobin (6.3 ${\pm}$ 0.8%) and plasma triglyceride levels (99.4 ${\pm}$ 15.0mg/dL) of the Chinese herb group were not significantly different from those of the control group (6.7 ${\pm}$ 0.7% and 108.8 ${\pm}$ 11.0mg/dL). Thus, the Chinese herb mixture could be useful in the treatment of diabetes and cardiovascular complications of diabetes.

Evaluation of Cat Brain infarction Model Using MicroPET (마이크로 PET을 이용한 고양이 뇌 경색 모델의 평가)

  • Lee, Jong-Jin;Lee, Dong-Soo;Kim, Yun-Hui;Hwang, Do-Won;Kim, Jin-Su;Lim, Sang-Moo;Chung, June-Key;Lee, Myung-Chul
    • The Korean Journal of Nuclear Medicine
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    • v.38 no.6
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    • pp.528-531
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    • 2004
  • Purpose: PET has some disadvantage in the imaging of small animal due to poor resolution. With the advent of microPET scanner, it is possible to image small animals. However, the image quality was not good enough as human image. Due to larger brain, cat brain imaging was superior to mouse or rat. In this study, we established the cat brain infarction model and evaluate it and its temporal charge using microPET scanner. Materials and Methods: Two adult male cats were used. Anesthesia was done with xylazine and ketamine HCl. A burr hole was made at 1cm right lateral to the bregma. Collagenase type IV 10 ${\mu}l$ was injected using 30 G needle for 5 minutes to establish the infarction model. $^{18}F$-FDG microPET (Concorde Microsystems Inc., Knoxville, TN) scans were performed 1, 11 and 32 days after the infarction. In addition, $^{18}F$-FDG PET scans were performed using human PET scanner (Gemini, Philips medical systems, CA, USA) 13 and 47 days after the infarction. Results: Two cat brain infarction models were established. The glucose metabolism of an infarction lesion improved with time. An infarction lesion was also distinguishable in the human PET scan. Conclusion: We successfully established the cat brain infarction model and evaluated the infarcted lesion and its temporal change using $^{18}F$-FDG microPET scanner.

The Studies on the Development of Low Irritable Preservative System with Phenoxyethanol in Cosmetics (Phenoxyethanol을 이용한 저자극 방부시스템 개발에 관한 연구)

  • Ahn, Gi-Woong;Lee, Chn-Mong;Kim, Hyeong-Bae;Jeong, Ji-Hen;Jo, Byoung-Kee
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.31 no.1 s.49
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    • pp.43-49
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    • 2005
  • Recently, according as people who have sensitive skin increase, we've been giving more importance to the safety of cosmetics. Especially, preservative is known to be one of the main stimuli which cause side-effects of cosmetics. However, there have been few reports describing cell cytotoxicity, skin penetration, oil-aqueous phase partition, anti-microbial activity of preservatives and their correlation with skin irritation. The study is aimed to develop low irritable preservative system with phenoxyethanol, one of the most commonly used preservatives in cosmetics, considering various factors mentioned above. According to our results of cell cytotoxicity against human normal fibroblasts by means of MTT assay, phenoxyethanol showed the lowest cytotoxicity when compared to other preservatives tested (cytotoxicity: pro-pylparaben > butylparaben > ethylparaben > methylparaben > triclosan > phenoxyethanol), but human patch test for assessing shin primary irritation revealed that phenoxyethanol has higher skin irritation than methylparaben and triclosan. We performed in vitro skin penetration test using horizontal Franz diffusion cells with skin membrane prepared from hairless mouse (5 ${\~}$ 8 weeks, male) to evaluate the rate of skin penetration of preservatives. From the results, we found that the higher irritable property of phenoxyethanol in human skin correlates with its predominant permeability (skin penetration: phenoxyethanol > methylparaben > ethylparaben > propylparaben > butylfaraben > triclosan). Therefore, we made an effort to reduce skin permeability of phenoxyethanol and found that not only the rate of skin penetration of phenoxyethanol but also its skin irritation is dramatically reduced in formulas containing oils with low polarity. In the experiments to investigate the effect of oil polarity on the oil-aqueous phase partition of phenoxyethanol, more than $70\%$ of phenoxyethanol was partitioned in aqueous phase in formulas containing oils with low polarity, while about $70 {\~} 90\%$ of phenoxyethanol was partitioned in oil phase in formulas containing oils with high polarity. Also, in aqueous phase phenoxyethanol showed greater anti-microbial activity. Conclusively, it appears that we can develop less toxic preservative system with reduced use dosage of phenox-yethanol and its skin penetration by changing oil composition in formulas.