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Antitumor Activity of K6, an Allylthiopyridazine Derivative, in Hep-G2 Cells-transplanted Nude Mice
채희열,신지순,김태명,권운,조영민,최은경,황석연,김윤배,강종구 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.1
In vitro cytotoxicity and in vivo growth-inhibitory effect of 3-methoxy-6-allylthiopyridazine (K6), an allylthiopyridazine derivative, were evaluated in human hepatocellular carcinoma Hep-G2 cell line and in nude mouse xenograft model, respectively, in comparison with doxorubicin. In vitro cytotoxicity, K6 (5-2,000 μM) and doxorubicin (0.05-10 μM) decreased tetrazolium conversion by viable cells to formazan in a dose-dependent manner. From a mechanistic study, the Hep-G2 cells exposed to K6 or doxorubicin underwent morphological changes, displaying elongation with filamentous protrusions. In addition, the cells showed chromatin condensation and fragmentation, producing apoptotic bodies. In vivo solid tumor xenograft model, the growth rate of tumor mass was significantly suppressed to the half level by daily oral administration of K6 (20-100 ㎎/㎏), which is comparable to the effect of intravenous treatment with doxorubicin (2 ㎎/㎏), resulting in the decrease in final tumor weights to 0.78 and 0.50 g by K6 (100 ㎎/㎏) and doxorubicin, respectively, compared with 1.32 g of control. Also, mean survival time of mice of control group (14.4 days) was doubled by treatment with K6 (27.2-29.4 days) or doxorubicin (28.8 days), leading to 100% increase in life span. Interestingly, daily oral treatment with a high dose (100 ㎎/㎏) of K6 did not induce testicular toxicity, in contrast to full degenerations of germ cells in atrophic testes intravenously exposed to doxorubicin at 4-6-day intervals, in addition to the emaciation and decrease in body weights of the animals. Taken together, K6, an allylthiopyridazine derivative originated from dially sulfide in garlic oil, could be a promising candidate for chemotherapy of hepatocellular carcinomas as an oral regimen. 키워드
고콜레스테롤혈증 토끼에서 녹차추출물의 동맥경화 치료효과
채희열(Hee-Youl Chai),권운(Woon Kwon),김태명(Tae Myoung Kim),김한얼(Haneul Kim),이남진(Nam Jin Lee),신지순(Ji-Soon Sin),이덕근(Deok Keun Lee),박종범(Jong Bum Park),박승경(Sung-Kyeong Park),황석연(Seock-Yeon Hwang),김윤배(Yun-Bae Kim 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.3
Cholesterol-lowering and antiatherosclerotic effects of green tea extract were evaluated in hypercholesterolemic rabbits produced by feeding on high-cholesterol diet. Male New Zealand White rabbits were fed on only hypercholesterol diet containing 1% cholesterol and 2% corn oil for 2 weeks, and then green tea extract (1%) or lovastatin (0.002 %) were added to the diet for additional 8 weeks. Blood cholesterol level was greatly increased by 2-week feeding on the hypercholesterol diet to 25 fold (mean 1,057.8 ㎎/㎗) of control level (42.5 ㎎/㎗), and maintained high for additional 8 weeks, in spite of slight reduction to 92.2 % of initial hypercholesterolemia. Such a hypercholesterolemia was significantly reduced by 8-week feeding on green tea extract and lovastatin to 62.6% and 67.4% of initial levels, respectively. Low-density lipoproteins were also markedly enhanced by hypercholesterol diet for 2 weeks to 34 fold (mean 533.3 ㎎/㎗) of control (15.8 ㎎/㎗), and increased further by 181.9 ㎎/㎗ during 8-week feeding on the diet. Compared to no effect of green tea extract (181.3 ㎎/㎗), lovastatin (63.0 ㎎/㎗) significantly attenuated the increase in the level of low-density lipoproteins during 8 weeks. On the other hand, triglycerides were not affected by hypercholesterol diet, and the level of high-density lipoproteins, which had been increased (3.6 fold of control) by hypercholesterol diet, were not considerably affected by green tea extract or lovastatin. Interestingly, thick atheromatous plaques on the wall of aorta of rabbits fed on hypercholesterol diet were markedly attenuated by green tea extract or lovastatin, leading to the decreases in athrosclerosis indices to 1.75 and 1.25, respectively, from 2.25 of rabbits fed on hypercholestrol diet alone. In addition, green tea extract lowered lipid deposition in hepatocytes, showing restricted distribution of foamy hepatocytes. Taken together, it is suggested that green tea extract exert antiatherosclerotic effect by reducing blood cholesterol level.
콜레스테롤 함유 식이 랫드에서 감귤껍질추출물 BNs-3 및 BNs-7의 항비만 효과
채희열(Hee-Youl Chai),신지순(Ji-Soon Sin),권운(Woon Kwon),최은경(Ehn-Kyoung Choi),조영민(Young Min Cho),장호송(Hu-Song Zhang),황석연(Seock-Yeon Hwang),복성해(Song-Hae Bok),김윤배(Yun-Bae Kim),강종구(Jong-Koo Kang) 한국독성학회 2003 Toxicological Research Vol.19 No.3
The protective effects of BNs-3 and BNs-7, extracts of citrous orange peel, on the obesity induced by ad libitum feeding a cholesterol-containing diet to rats were investigated. The animals<br/> were fed on the diet including cholesterol (0.5%) with or without the citrous orange peel extracts BNs-3 (5%) and/or BNs-7 (0.1%) for 8 weeks. The ad libitum feeding a diet containing cholesterol to<br/> rats from 6 weeks of age increased the body weight gain compared with that of rats fed on a normal diet. Such an increase in body weights was markedly attenuated by the addition of BNs-3 or BNs-7 to the diet. Especially, a combinational feeding on BNs-3 and BNs-7 significantly reduced the body weight gain below that of normal diet-fed animals. Interestingly, the weights of abdominal adipose tissues surrounding epididymides were greatly reduced by the citrous orange peel extracts, in parallel with the decrease in body weights. In addition, blood concentrations of lipids including cholesterol were also lowered by the combinational treatment with BNs-3 and BNs-7. Taken together, it is suggested that the obesity and overweight produced by unrestricted overfeeding on diet with cholesterol may be partially due to the accumulation of abdominal adipose tissues, around the epididymides in rats, and that citrous orange peel extracts might exert antiobese activities by reducing the adipose tissues as well as blood lipid concentrations.