• 대한본초학회지
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• 제24권3호
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• pp.1-12
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• 2009

Objectives : The objective of this study was to compare, the potency of toxicity of Cantharidin containing dried Mylabis phalerata (MP) extract and it's modifier. Methods ： They were monitored at dosage level 2,000, 1,000, 500, 250 and 125 mg/kg, respectively. Changes of body weight, clinical signs, mortality, LD50, macroscopic changes of gastrointestinal tract and liver were observed after single oral dose of test articles with changes of serum Gastrin and Somatostatin levels. Results ： Dosage-dependent decrease of body weight and/or gains were demonstrated in dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, the body weights were significantly increased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently detected clinical signs in dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these clinical signs dramatically were decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependent increase of mortality rates were observed in dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, the mortalities were significantly decreased compared to that of equal dosage group of dried MP extract-dosing group. The LD50 of dried MP extract in male mice was dramaticlly increased in their modify, 265.86 vs 426.99 mg/kg. Dosage-dependently increase of number of hemorrhagic and/or erythematous spots detected in the gastrointestinal tracts of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal spots were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently increase of degrees of enlargement and congestion detected in the liver of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal signs were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently increase of serum gastrin levels of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal increase were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Dosage-dependently increase of serum somatostatin levels of dried MP extract-dosing groups, were also detected in modified and dried MP extract-dosing groups at 2,000 and 1,000 mg/kg-dosing group. However, below 500 mg/kg-dosing group, these abnormal increase were dramatically decreased compared to that of equal dosage group of dried MP extract-dosing group. Conclusions ： The toxicity of dried MP extract was reduced by their modify.

• 생명과학회지
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• 제29권1호
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• pp.112-117
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• 2019

산수유(Corni Fructus)는 한국을 포함한 아시아 지역에서 오랫동안 전통 의약제로 광범위하게 사용되어 왔다. 최근 연구에 따르면 산수유는 항염증, 항산화, 면역기능 조절 및 항암활성 등과 같은 많은 효능을 가지는 것으로 알려져 있다. 그러나 산수유에 대한 독성 및 안전성에 대해서는 거의 알려져 있지 않은 실정이다. 따라서 본 연구에서는 산수유 열수 추출물(CF)을 대상으로 안전성을 확인하기 위하여 단회 경구 투여에 따른 독성 시험을 실시하였다. 이를 위하여 ICR 마우스를 대상으로 1,000, 2,000 및 5,000 mg/kg의 CF를 경구 투여하였으며, 투여 후 14일 동안의 치사율, 체중 변화, 임상증상, 음수율 및 사료섭취량과 함께 부검 소견, 장기무게 변화, 혈액학 및 혈액생화학적 검사를 실시하였다. 실험 결과에 의하면 CF 투여에 따른 치사율, 임상증상, 체중 및 부검 소견 상의 유의적인 변화는 관찰되지 않았다. 또한 CF 투여에 따른 각 장기의 무게, 혈액학적 및 혈청학적 임상 화학적 지표에도 유의적인 변화는 관찰할 수 없었다. 따라서 CF 단회 경구 투여에 따른 치사량이 5,000 mg/kg 이상일 것으로 추정되어 ICR 마우스에 대하여 급성 독성이 없는 비교적 안전한 물질이라는 것을 알 수 있었으며, 향후 천연 식의약 소재로서의 효능 규명을 통한 활용이 기대된다.

• 농약과학회지
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• 제11권4호
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• pp.261-267
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• 2007

국내서식 물벼룩종을 이용한 표준생태독성시험법 개발을 위한 기초연구로서 4종의 한국산 물벼룩 Daphnia sp., Daphnia obtusa, Moina macrocopa, Simocepholus vetulus과 국제표준종 Daphnia magna대한 5종 농약에 대한 급성독성반응을 조사하였다. Diazinon의 D. magna, D. obtusa, Daphnia sp., M. macrocopa, S. vetulus에 대한 48시간 $EC_{50}$은 각각 0.81, 1.7, 2.2, 4.5, $23\;{\mu}g\;L^{-1}$였다. Carbofuran의 D. obtusa, Daphnia sp., D. magna, M. macrocopa, S. vetulus에 대한 48시간의 $EC_{50}$은 각각 6, 10, 19, 211, $316\;{\mu}g\;L^{-1}$였다. 가장 민감한 D. obtusa와 가장 둔감한 S. vetulus간의 독성치 차이는 52.7배로 시험에 사용한 5종의 농약 중 가장 큰 차이를 보였다. Fenpropathrin은 시험에서 사용한 계통별 농약 5종 중에 가장 높은 독성을 보였는데 D. magna, Daphnia sp., D. obtusa, M. macrocopa, S. vetulus에 대한 48시간 $EC_{50}$은 각각 0.27, 0.56, 0.8, 1.6, $3.4\;{\mu}g\;L^{-1}$이었다. Iprodione은 M. macrocopa에 대한 독성이 가장 강해서 48시간의 $EC_{50}$이 $0.16\;{\mu}g\;L^{-1}$이었으며 Daphnia sp., S. vetulus, D. magna, D. obtusa의 48시간의 $EC_{50}$은 각각 0.24, 1.18, 1.38, $1.62\;{\mu}g\;L^{-1}$으로 독성이 낮았다. Myclobutanil은 본 시험에서 사용한 계통별 농약 5종 중에 가장 독성이 낮았는데 5종의 물벼룩 중에 D. obtusa가 이 농약에 대하여 가장 민감한 반응을 보였으며 48시간 $EC_{50}$은 $5.4\;{\mu}g\;L^{-1}$이었다. 물벼룩 종간에 1.3배에서 많게는 52.7배까지 급성 독성값의 차이를 보여 특정농약에 대한 종간 감수성차이를 확인할 수 있었으나 여러 농약에 대한 급성독성반응의 상관성을 비교한 결과에서는 약제별 독성반응이 매우 유사함을 보여주었다. 특히 D. magna와 국내서식 Daphnia속 2종 물벼룩의 독성반응은 매우 유사하며 비교적 농약에 대한 민감성도 높음을 보여 주었다. Ipodione에 대한 감수성은 국내종인 M. macrocopa가 가장 높아 국제종인 D. magna가 항상 농약에 대한 민감성이 높게 나타나는 것은 아님을 알 수 있었다. 시험에 사용한 물벼룩중 S. vetulus는 농약에 대한 민감성이 현저히 낮아 표준독성시험을 위한 생물종으로 활용하는 것은 바람직하지 않을 것으로 판단된다.

• Applied Biological Chemistry
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• 제18권2호
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• pp.71-97
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• 1975

To improve the food qualities in Korea, two hundred and fourtynine kinds of food additives have been allowed in food processing, of which one hundred and nineteen kinds could be used under the limitted conditions. Hence, in practical uses in food processing, many kinds of them are mixed at random within the permitted amounts for their special purposes. For last several years, many kinds of the food additives were prohibited because they have been proved to be toxic even with the single dose. Until recently a few studies on the toxicity in the mixture of food additives were reported, however, they were shown to be no severe additional effect on the animal. This study was performed to see if any elevation of chronic or subacute toxicity of food additives occur especially when they are mixed with each other, using three kinds of food additives (DHA, AF-2, BHT) most widely used as food preservatives, antiseptics and antioxidants. One hundred and fifty young male rats were taken and divided into ten feeding groups, one first control group (food additives blank), three second control groups (DHA 0.1%, AF-2 0.1%, BHT 0.5%), three mixture groups of low level (mixture of each 60% of two second control level) and three mixture groups of high level (mixture of each 90% of two second control level). As the methods of biological and clinical tests, the change of body weight (growth rate), daily intake of diets, organ to body weight ratio, histopathological findings of organs, hematological observation, liver and kidney function tests were checked three times during the periods of 24 weeks. The following results were obtained. 1. The low level group of DHA, AF-2 mixture and DHA, BHT mixture revealed a little retardation in growth rate than the first control group, however, they were similar to the second controls, while all the mixture groups of high level showed a more remarkable retardation than the first and second controls. 2. Average daily intake of the diets was the same in each group, showing a similar decreasing tendency (70-100g/kg of body weight) in accordance with the growth rate. It was observed that there are no differences in the taste and appetite in each group of rats. 3. Abnormal enlargements of kidney and lung were not seen in all the mixture groups compared with the controls, while a slight hepatomegaly was observed in all mixture groups of low level as in the second controls. Significant differences (almost 1% level) were observed between the high level groups and the first control group. 4. Histopathological effects of the food additives on lung, kidney and liver tissues were found in all mixture group of high level. The less frequencies of the same effects were also seen in the low level groups. 5. The esterified cholesterol to total cholesterol ratio in the mixture groups of high level showed a little lower values, and the activities of serum glutamate oxaloacetate transaminase and alkaline phosphatase decreased almost with significance of 5% level compared with the first control group. The serum A/G ratio in the mixture groups also decreased. The results demonstrated that the liver function was decreased in the mixture groups compared with the controls. 6. In all groups throughout the test period, kidney functions (concentration of protein and creatinine excreated per hour in urine and renal filtration rate) were shown almost as normal as the first control. 7. Average values of hematocrit, erythrocytes and leucocytes in the mixture groups were in the normal ranges as in the controls, which denotes that the production of blood cells in bone marrow were also normal in all groups. With the above results, it is concluded that when the food additives (DHA, AF-2, BHT) were given together to the rats in several combinations even in less amount, they showed more toxic signs than the single doses.

• 한국응용과학기술학회지
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• 제35권1호
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• pp.254-262
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• 2018

구아바 잎 추출물의 항산화 활성과 항염증 소재로서의 활용 가능성을 확인하고자 하였다. 구아바 잎 추출물의 총 폴리페놀 함량, 총 플라보노이드함량, RAW 264.7 세포에 대한 세포 독성 및 NO 생성 억제를 통한 항염증 효과, 피부에 대한 안전성 평가를 실시하였다. 본 실험 결과, 총 폴리페놀과 플라보노이드의 함량이 각 126.4 mg/g, 223.17 mg/g으로 높은 함량을 확인하였다. 대식세포인 264.7세포에 대한 세포 독성이 나타나지 않았으며 NO 생성을 농도 의존적으로 억제되는 것을 확인하였다. 구아바 잎 추출물을 함유한 크림을 제조하여 1차 첩포 테스트를 실시하여 피부 안전성을 확인한 결과 첩포 24 시간 후와 첩포 제거 24 시간 후에도 피부에 대한 자극은 확인되지 않았다. 이러한 결과를 종합해 볼 때 높은 총 폴리페놀과 플라보노이드의 함량으로 인한 항산화 활성이 우수하고, 세포에 대한 피부 독성이 적고 NO 생성 억제 효과가 확인됨에 따라 항산화 및 항염증 효과를 가진 소재로서의 활용 가능성을 확인하였다.

• 환경생물
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• 제18권4호
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• pp.377-385
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• 2000

인위적인 산성스트레스가 담수산 소백옆새우(Gammarus sobaegensis Ueno)에 미치는 영향을 정체성 수조건 하에서 급, 만성 생태독성실험을 통해 알아보았다. 급성독성 실험 시 pH 3 대역에서의 반수치사시간($LT_{50}$)은 평균 0.271($\pm$0.146)day로 개체의 크기 또는 먹이의 유무 그리고 주변 환경에 대한 적응능력에 관계없이 일정한 모습을 나타내고 있었다. pH4.0대역에서의 $LT_{50}$은 0.812($\pm$0.377) day로 연장되는 것이 확인되었다. 만성 독성실험의 경우 본 종의 반수치사시간은 pH 3.0일 때 약 6-7 day로 평균 6.313 ($\pm$0.828) day 인 것으로 나타났으며, pH 5.0일 때는 평균 9.475($\pm$4.881)day의 오랜 적응 기간을 갖는 것으로 확인되었다. 이러한 차이는 먹이의 공급유무에 따라 변동이 있다는 것을 알 수 있었고, 또한 주변 환경에 적응이 잘 된 개체일수록 오랜 기간동안 생존한다는 것을 알 수 있었다. 그리고 급, 만성 pH스트레스가 가해진 소백옆새우(G. sobaegensis)의 제 2아가미 표면조직에서 심한 주름현상을 확인할 수 있어, 결국 산성스트레스는 소백옆새우(G. sobaegensis)에 있어서 급성뿐만 아니라 만성적인 영향에서도 최종적으로는 매우 치명적으로 작용한다는 사실을 알 수 있었다.

• 동의생리병리학회지
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• 제16권2호
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• pp.353-358
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• 2002

To test the protective effect of herbal medicine against oxygen free radical-induced myocardiotoxicity, cytotoxicity of xanthine oxidase/hypoxanthine (XO/HX) was examined using MTT, TBARS, and beating rate assay in the presence of water extract of Sujeom-san(SJS) or single consituents of its prescription. Myocardial toxicity was evaluated in neonatal rat myocardiocytes in cultures. In the present paper, XO/HX resulted in a decrease in viability and beating rate and increases in lipid peroxidation in cultured myocardial cells. In the effect of SJS water extract, it showed effects from the cardiocytotoxicity induced by XO/HX treatment such as increases in beating rate and decreases in lipid peroxidation. In the effect of Rhizoma Corydalis (RC), Faeces Trogopterori (FT), Fructus Amomi Tsaoko (FAT) and Myrrha on the cardiocytotoxicity, they were significantly effective in blocking the XO/HX-induced cardiocytotoxicity by increase of beating rate in FAT and FT group as well as decrease of lipid peroxidation in FT and RC group. These results show that oxygen free radical elicits toxic effects in cultured myocardial cells derived from neonatal rat, and suggest that water extract of Sujeomsan, Rhizoma Corydalis, Faeces Trogopterori, Fructus Amomi Tsaoko or Myrrha is very effective in the prevention of xanthine oxidase/hypoxanthine- induced cardiotoxicity.

• Natural Product Sciences
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• 제23권2호
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• pp.132-138
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• 2017

This study was designed to investigate the synergetic hepatoprotective effects from a mixture of Korean Red Ginseng and Pueraria Radix on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in mice. Liver toxicity was induced by intraperitoneal administration of $CCl_4$ (0.6 mg/kg) in 12 groups of ICR mice. The negative control group was given $CCl_4$ without test samples and the normal group was given no treatment. Among treatment groups, the RGAP treatment (Korean Red ginseng acetic acid extract : Pueraria radix water extract, w/w, 38.4:57.6) decreased $CCl_4$-elevated ALT (101.60 IU/L), AST (833.89 IU/L), and LDH (365.02 IU/L) levels in the serum, and increased the SOD (11.03 unit/mg protein) and CAT (0.37 unit/mg protein) levels and the LPO levels ($59.09{\mu}M/g$ tissue) more than that in the mice group with $CCl_4$-induced control group hepatotoxicity. These results suggest that administration of a mixture of Korean Red ginseng and Pueraria radix decreases $CCl_4$-induced liver damage and enhances antioxidant activity in mice and imply that administration of the mixture in a certain ratio is more effective than single administration of either Korean Red ginseng or Pueraria radix alone.

• 대한한방내과학회지
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• 제25권1호
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• pp.92-105
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• 2004

In order to evaluate the anti-tumor and synergic effect of BoJungIkKeeHapDaeChilKi-Tang on doxorubicin, the inhibitory concentration(IC), IC50 and IC90 of single use of doxorubicin and BoJungIkKeeHapDaeChilKi-Tang with their concomitant treatment against MKN-45(Human stomach carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst MKN-45 cell lines. BoJungIkKeeHapDaeChilKi-Tang has only mimic direct anti-tumor effect against to MKN-45 cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that BoJungIkKeeHapDaeChilKi-Tang extracts were reduced by the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubicin and BoJungIkKeeHapDaeChilKi-Tang extracts.

• 대한한의학방제학회지
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• 제12권2호
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• pp.119-137
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• 2004

In order to evaluate the anti-tumor and synergic effect of Soonkiwhajungtang with doxorubicin, the inhibitory concentration(IC), $IC_{50}\;and\;IC_{90}$ of single use of doxorubicin and Soonkiwhajungtang with their concomitant treatment against Colon-26(Murine Rectum Carcinoma) was observed using MTT(Microculture Tetrazolium test) assay. In addition, their anti-tumor effects were also observed in the xenograft nude mice models agianst to Colon-26 cell lines. Soonkiwhajungtang has only mimic direct anti-tumor effect against to Colon-26 cell lines but they were decreased general depressed signs induced by implantation of tumor cell lines and increased the total WBC and lymphocyte numbers. So, it is considered or expected that Soonkiwhajungtang extracts were reduced the critical toxicity of doxorubicin and shows favorable synergic effect with doxorubidn and Soonkiwhajungtang extracts.