Zucker rats에서 고지방식이에 의해 유도된 비만에 대한 활기단 SJ-201의 개선효과

조정희(Jung-Hee Cho),이남진(Nam Jin Lee),홍성희(Seong-Hee Hong),김동규(Dong Kyu Kim),신선희(Sunhee Shin),박정휘(Jung-Hui Park),강종구(Jong-Koo Kang),김윤배(Yun-Bae Kim),황석연(Seock-Yeon Hwang) 한국실험동물학회 2005 Laboratory Animal Research Vol.21 No.2

This study was performed to investigate the anti-obesity effect of Hwalgidan SJ-201 in high-fat diet-fed Zucker Fa/- rats. Obesity was induced by feeding on high-fat diet containing 3% corn oil and 1% cholesterol for 8 weeks, in which Hwalgidan SJ-201 (3%) was added to the diet for the treatment group. The rats fed on the high-fat diet showed increased gain of body weights, leading to enhanced feed efficiency ratio. In addition, cholesterol, low-density lipoproteins (LDL), alanine transaminase, aspartate transaminase, total proteins and creatinine were increased, in comparison with decrease in high-density lipoproteins (HDL), in male rats. In females, cholesterol, LDL, triglycerides, lactate dehydrogenase and creatinine were enhanced, in contrast to lowered level of HDL. Moreover, high-fat diet induced hepatic lipid peroxidation, resulting in increased relative liver weights. Such changes in body weights as well as parameters indicating obesity and hepatic injury were attenuated by feeding on Hwalgidan SJ-201, although there were some fluctuation of biomarkers and gender differences in the response to the diet and Hwalgidan SJ-201. Taken together, it is suggested that Hwalgidan SJ-201 has potential for improving high-fat diet-induced obesity and ensuing hepatic burden by regulating lipid profiles and radical reactions.

토끼에서 고콜레스테롤 유도 동맥경화에 대한 활기단 SJ-101의 개선효과

조정희(Jung-Hee Cho),이남진(Nam Jin Lee),채희열(Hee-Youl Chai),김태명(Tae Myung Kim),박정휘(Jung-Hui Park),강종구(Jong-Koo Kang),김윤배(Yun-Bae Kim),황석연(Seock-Yeon Hwang) 한국실험동물학회 2005 Laboratory Animal Research Vol.21 No.2

The purpose of this study was to confirm the improving effect of the Hwalgidan SJ-101 on hypercholesterolemia and ensuing atherosclerosis in rabbits. Male New Zealand White rabbits were fed on only hypercholesterol diet containing 1% cholesterol and 2% corn oil for 2 weeks, and then Hwalgidan SJ-101 (1% or 3%) or lovastatin (0.002%) were added to the diet for additional 8 weeks. Blood cholesterol levels, especially low-density lipoproteins (LDL), were greatly increased by 2-week feeding on the hypercholesterol diet to 25 - 35 fold of control, and further increased during additional 8 weeks, in contrast to reduction of high-density lipoproteins (HDL). Such a hypercholesterolemia was significantly reduced by 8-week feeding on Hwalgidan SJ-101 or lovastatin. In addition, the hypercholestrol diet-induced decrease in HDL and increase in triglycerides were reversed by Hwalgidan SJ-101 or lovastatin. Moreover, thick atheromatous plaques on the wall of aorta of rabbits fed on hypercholesterol diet were markedly attenuated by Hwalgidan SJ-101 or lovastatin, leading to the decreases in atherosclerosis indices to 2.0, respectively, from 2.75 of rabbits fed on hypercholesterol diet alone. In addition, Hwalgidan SJ-101 lowered lipid deposition in hepatocytes, showing restricted distribution of foamy hepatocytes. Interestingly, however, lovastatin caused hepatic centrilobular congestion, leading to great increase in serum alanine transaminase and aspartate transaminase activities, in contrast to normal levels in Hwalgidan SJ-101-treated animals. In conclusion, the results suggest that Hwalgidan SJ-101 improves hyperlipidemia and ensuing atherosclerosis, without hepatotoxicity, probably by both controlling lipid metabolism and reducing free radical reactions.

고지방식이에 의해 비만이 유도된 Zucker Rats에서 상백피분말의 비만 개선효과

홍성희 ( Seong Hee Hong ),김동규 ( Dong Kyu Kim ),이남진 ( Nam Jin Lee ),조정희 ( Jung Hee Cho ),강종구 ( Jong Koo Kang ),김윤배 ( Yun Bae Kim ),박정휘 ( Jung Hui Park ),황석연 ( Seock Yeon Hwang ) 대한임상검사과학회 2005 대한임상검사과학회지(KJCLS) Vol.37 No.2

This study was performed to investigate the anti-obesitic effect of mulberry root-bark on male and female Zucker FA/FA or FA/fa rats. Obesity in the rats was induced by feeding high-lipid diet contained 3% corn oil and 1% cholesterol. Experimental groups in male and female rats were assigned to normal diet group (normal control), high-lipid diet group(positive control) and 3% mulberry root-bark powder in high-lipid diet group (MRC). The mulberry treated-group showed decreases of body weight, FER (food efficiency ratio) value and lipid peroxidation in the liver and increase of high density lipoprotein cholesterol (HDL-C) value, compared with positive control groups. Our findings suggest that mulberry root-bark has a potential role in preventing or improving obesity from the following points of view, body weight, serum lipids and antioxidant enzyme activities.

고지혈증 토끼에서 상백피 에탄올추출물의 동맥경화 개선효과

홍성희(Seong-Hee Hong),채희열(Hee-Youl Chai),김태명(Tae Myoung Kim),이남진(Nam-Jin Lee),김동규(Dong-Kyu Kim),조정희(Jung-Hee Cho),박정휘(Jung-Hui Park),김윤배(Yun-Bae Kim),강종구(Jong-Koo Kang),황석연(Seock-Yeon Hwang) 한국실험동물학회 2005 Laboratory Animal Research Vol.21 No.3

Hyperlipidemia is one of the risk factors for atherosclerosis. This study was conducted to investigate the cholesterol-lowering and antiatherosclerotic effect of Mori radicis cortex-ethanol extracts (MRC-EE) in hypercholesterolemia produced by feeding on high-cholesterol diet in rabbits. Male New Zealand White rabbits were fed on only high-fat fed diet containing 1% cholesterol and 2% corn oil for 2 weeks, and then MRC-EE (1% or 3%) or lovastatin (0.002%) were added to the diet for additional 8 weeks. The levels of blood cholesterol, low-density lipoproteins (LDL) and high-density lipoproteins (HDL) were greatly increased by 2-week feeding on the high-fat diet, compared with those of animals fed on normal diet. Blood concentrations of cholesterol, LDL and triglycerides further increased during additional 8-week feeding on high-cholesterol diet alone, in contrast to significant decrease in HDL level. In comparison, the levels of cholesterol and LDL were reduced by lavastatin and MRC-EE, in addition to less-severe decrease in HDL contents. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) significantly increased in lovastatin-treated rabbits, but not in MRC-EE-fed animals. In addition, MRC-EE (3%) lowered lipid deposition in hepatocytes, showing restricted distribution of foamy hepatocytes, in constrast to hepatic centrilobular congestion and hepatotoxicity caused by lovastatin. The thick atheromatous plaques (mean score 2.75) on the aortic wall of rabbits fed on high-fat diet were markedly attenuated by MRC-EE (3%) or lovastatin, leading to the decreases in athrosclerosis indices to 2.0. These results suggest that MRC-EE (3%) exerts antiatherosclerotic effect by reducing atherosclerosis index without hepatotoxicity.

상백피의 4주 반복투여독성 평가

황석연(Seock-Yeon Hwang),권운(Woon Kwon),채희열(Hee-Youl Chai),조영민(Young-Min Cho),이남진(Nam Jin Lee),류재면(Jae Myun Ryu),신지순(Ji Soon Sin),김태명(Tae Myung Kim),조정희(Jung-Hee Cho),김은주(Eun Ju Kim),박정휘(Jung-Hui Park),강종 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.3

Four-week repeated-dose toxicity study was performed to confirm the safety of the water extract of Mori radicis cortex single (MRCS) or mixed (MRCM) compound. Male Sprague-Dawley rats were orally administered with MRCS or MRCM at doses of 0.5, 1.0 or 2.0 g/㎏/day for 28 days. In the results, there were no significant differences in the body weight gain between vehicle control and MRCS or MRCM treatment groups. Also, no significant changes in daily feed intake and water consumption were observed throughout the experimental period. In hematological analysis, there was a trend of increases in red blood cells at 0.5 and 1.0 g/㎏ of MRCM and in hemoglobin at 0.5 g/㎏ of MRCM, although such changes were in normal ranges. In addition, white blood cells, especially neutrophils, slightly increased, without statistical significance, following treatment with MRCS or MRCM. Interestingly, serum biochemical parameters including aspartate transaminase and alanine transaminase, related to hepatic injuries, decreased at all doses after 28-day treatment with MRCS or MRCM, suggestive of protective effects against tissue damage. No significant changes in organ weights were observed, in accordance with normal features in gross and microscopic findings. Taken together, it is suggested that repeated treatment with the extract of Mori radicis cortex or its mixed compound, available in oriental clinics, may not exert considerable side effects.

가미귀비탕의 4주 반복투여독성 평가

황석연(Seock-Yeon Hwang),권운(Woon Kwon),채희열(Hee-Youl Chai),조영민(Young-Min Cho),류재면(Jae Myun Ryu),김동규(Dong Kyu Kim),신지순(Ji Soon Sin),김태명(Tae Kyung Kim),조정희(Jung-Hee Cho),신선희(Sunhee Shin),박정휘(Jung-Hui Park) 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.3

Four-week repeated-dose toxicity of Kamiguibitang was investigated in rats. Male Sprague-Dawley rats were orally administered with Kamiguibitang at doses of 200, 800, 1,600 or 3,200 ㎎/㎏/day or its vehicle for 28 days. There were no significant differences in the body weight gain between vehicle control and Kamiguibitang-treated groups. Significant changes in daily feed intake and water consumption were not observed throughout the experimental period. There were trends of increase in platelets and white blood cells, in parallel with increases in serum globulin level and spleen weight, suggestive of inflammatory response and/or immune enhancement. Serum parameters of hepatic and renal injuries, such as aspartate transaminase, alanine transaminase, alkaline phosphatase, cholesterol, triglyceride, creatinine, phosphorus, calcium, sodium and potassium, also increased at low doses (200-800 ㎎/㎏) of Kamiguibitang, although the levels were suppressed at high doses (1,600-3,200 ㎎/㎏). However, no gross and histopathological lesions were seen at all doses. Based on the results, no observed adverse effect level (NOAEL) of Kamiguibitang was found to be lower than 200 ㎎/㎏, which is comparable with clinical dose (100 ㎎/㎏) in human. In spite of the relatively-low NOAEL, it is suggested that repeated treatment with Kamiguibitang may not exert considerable adverse effects, as inferred from that major hematological and blood biochemical changes were results of pharmacological effectiveness on immunomodulation, and that no histopathological lesions were exerted up to 32 folds of clinical dose (3,200 ㎎/㎏),

상엽의 4주 반복투여독성 평가

황석연(Seock-Yeon Hwang),권운(Woon Kwon),채희열(Hee-Youl Chai),조영민(Young-Min Cho),이남진(Nam Jin Lee),류재면(Jae Myun Ryu),신지순(Ji Soon Sin),김태명(Tae Myung Kim),조정희(Jung-Hee Cho),장자영(Ja Young Jang),박정휘(Jung-Hui Park) 한국실험동물학회 2004 Laboratory Animal Research Vol.20 No.3

The purpose of this study was to confirm the safety of the water extract of Mori folium single (MFS) or mixed (MFM) compound. Male Sprague-Dawley rats were orally administered with MFS or MFM at dose levels of 0.5, 1.0 or 2.0 g/㎏/day for 4 weeks. As results, there were no significant differences in the body weight gain between vehicle control and MFS or MFM-treated rats. Also, significant changes in daily feed intake and water consumption were not observed during the experimental period. In hematological analysis, there was a trend of decrease in prothrombin time, in contrast to a slight delay in activated partial thromboplastin time following MFS or MFM treatment. And white blood cells (WBC), especially lymphocytes, somewhat increased. In serum biochemical analysis, aspartate transaminase, alanine transaminase and alkaline phosphatase, related to hepatic injuries, decreased. Also, renal and pancreatic toxicity parameters such as blood urea nitrogen, creatinine and amylase decreased by MFS or MFM treatment. Interestingly, serum globulin fraction in total proteins increased, suggestive of an immunopotentiation effect, in accordance with the increase in WBC. There were no significant changes in organ weights, and no gross and histopathological lesions were observed. Taken all together, it is proposed that repeated treatment with the extract of Mori folium or its mixture, available in oriental clinics, may not exert considerable adverse effects, and that rather protect against tissue injuries and enhance immune functions.

葦莖湯·加味葦莖湯의 A549에 對한 細胞毒性과 S-180에 對한 抗癌效果

김성훈,박정휘,박경식,김동희 대한동의병리학회 1995 동의생리병리학회지 Vol.9 No.2

연구배경 : 폐암은 최근 암사망률 중 17%로 위암과 간암에 이어 3위를 차지하고 있어 이의 치료와 연구는 중요한 과제로 등장하고 있다. 따라서 한의학적 측면에서 폐암에 해당되는 문헌을 찾아보아 이중 폐옹에 사용되는 길경탕과 최근에 각종 암에 다용되는 어성초, 白花蛇설초를 가미한 가미길경탕의 항암 효과 및 항암제와의 병용효과등을 현대적인 실험을 통하여 규명, 폐암에 대한 치료법을 제시하고자 함 방법 : in vitro에서 사람의 肺癌株인 A549에 對한 抗腫瘍效果와 cyclophosphamide(CPM), cisplatin(CPT), adriamycin(ARM), 5-fluorouracil(5-FU) 등의 4種 抗癌劑와의, 相乘作用을 살펴보고, ICR생쥐에 S-180을 腹腔 注射한 後 實驗 藥物을 口腔 投與하여, 生命延長率, 體重變化 및 血液檢査 등을 실시하였다. 결과 : 葦莖湯, 葦莖湯加魚腥草, 葦莖湯家伯花蛇舌草는 모두 肺癌에 對한 抗腫瘍效果가 認定되며, cyclophosphamide나 cisplatind을 倂用하거나 魚腥草나 白花蛇舌草를 加味하였을 경우 보다 效果的인 것으로 나타났다. In order to prove the antitumor effect of Wekyungtang(WKT) that was originated in Bigeubchunkeumyobang(備急千金要方), Wekyungtang with Houttuyniae Herba(WKT-I) and Wekyungtang with Oldenlandiae diffusae Herba(WKT-Ⅱ) on human pulmonary tumor cells experimentally, the studies were done. We evaluated the cytotoxic activity against A549 as well as the synergistic effects with anticancer drugs such as cyclophophamide(CPM), cisplatin (CPT), adriamycin (ARM) and 5-fluorouracil(5-FU) in vitro, and measured body weight, survival time, hematological changes in ICR bearing S-180. The results were obtained as follows: 1. IC50 against A549 was 16.24ug/ml in cyclophophamide (CPM), 8.01ug/ml in cisplatin(CPT), 8.39ug/ml in adriamycin(ARM) and 3.13 in 5-fluorouracil (5-FU) respectively. 2. Inhibitory effect on the adhesion of A549, the ratio of No. of antiadhesive cells to adhesive cells was 26.8/73.2 in WKT, 30.42/69.58 in WKT-Ⅰ and 35.12/64.88 in WKT-Ⅱ at the concentrations of 10-³g/ml, which indicates that antiadhesive effect was shown in the order of WKT-Ⅱ, WKT-Ⅰ, WKT. 3. In vitro the concentrations showing inhibitory growth rate below 55% of control against A549 was recognized in concentration of 10-³g/ml of WKT, the synergistic effect with CPM was shown in the concentration of 10-5 g/ml above of WKT, concentrations of WKT-Ⅰ, 10-³g/ml of WKT-Ⅱ, the syneristic effect with CPT was shown in the concentration of 10-5 g/ml above of WKT-Ⅱ, the synergistic effect with ARM was shown in concen -tration of 10-³g/ml of WKT-Ⅰ, WKT-Ⅱ, the synergistic effect with 5-FU was shown in concentration of 10-³g/ml WKT, WKT-Ⅰ, which indicated that CPT, CPM had the synergistic action with WKT. 4. In vivo, the gaining of body weight was significantly suppressed in all groups as compared with control group bearing S-180 and ILS was 10.45% in WKT, 16.43% in WKT-Ⅰ, 21.82% in WKT-Ⅱ respectively. 5. The number of platelet was significantly increased in WKT, WKT-Ⅰ and platelet aggregation was significantly increased in all roup as compared with control group. From the above results it was concluded that Wekyungtang and Kami-Wekyungtang had antitumor effect against A549 and wekyungtang combined with Houttuyniae Herba or Oldenlandiae difusae Herba was more effective than wekyungtang only, also cyclophophamide(CPM), cisplatin(CPT) exerted the more synergistic effect in the anticancer drugs.