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3T3-L1 지방세포 및 제2형 당뇨 마우스 모델에서 건지황 열수 추출물의 항당뇨 효능 연구
조란(Ran Jo),민정란(Jeong-Ran Min),정상희(Sang-Hee Jeong) 한국식품영양과학회 2018 한국식품영양과학회지 Vol.47 No.10
본 연구에서는 대표적인 한의서인 동의보감 및 방약합편에 수재된 농식품 소재 중 당뇨병과 같은 대표증상에 효과가 있는 것으로 소개된 건지황에 대해 3T3-L1 지방세포와 제 2형 당뇨질환모델인 C57BLKsJ-db/db 마우스에서 항당뇨 효과를 조사하였다. 건지황 열수 추출물을 제조하여 3T3-L1 지방세포에서 포도당 흡수능을 관찰한 결과, 3T3-L1 지방세포의 인슐린 감수성을 향상시켜 세포 내로의 포도당 흡수를 대조군 대비 약 2배 증가시켰다. 제2형 당뇨모델인 C57BLKsJ-db/db 마우스에 양성치료약물인 metformin(300 mg/kg bw/d), pioglitazone(20 mg/kg bw/d)과 건지황 열수 추출물(50, 500 mg/kg bw/d)을 4주간 각각 경구 투여한 후 항당뇨 효능을 평가한 결과, 체중감소량의 변화 없이 식이섭취량 및 음수섭취량이 감소하는 경향을 나타내었다. 공복혈당 및 HbA1c 수준은 건지황 열수 추출물을 투여했을 때 당뇨대조군에 비하여 유의적으로 감소시켰지만 경구 내당능은 당뇨대조군에 비하여 유의한 차이는 없었지만 개선하는 경향이 있었다. 혈중 인슐린 및 HOMA-IR 수준은 당뇨대조군에 비해 양성대조군 및 건지황 투여군에서 현저하게 낮은 수치를 나타내었으며, 혈중 중성지방 및 HDL-콜레스테롤 함량은 당뇨대조군에 비해 유의한 변화는 없었지만 총 콜레스테롤 농도는 유의한 감소를 나타내었다. 또한 조직에서 GCK mRNA 및 SLC2A2 mRNA 발현 정도가 유의적으로 증가하였으며, 특히 RG 500 mg/kg bw 투여군에서 제2형 당뇨병의 치료제인 Met 투여군과 비슷한 수준의 GCK 증가 효과가 확인되었다. 이러한 결과로 건지황 열수 추출물은 당뇨 증상 중 음수량, 음수횟수 증가 등을 완화시키고 지질대사 이상을 조절하면서 인슐린저항성을 감소시켜 혈당을 개선하므로 항당뇨 생리활성을 나타내는 식품소재로써 당뇨 개발의 가능성이 있을 것으로 사료되었다. Type 2 diabetes mellitus is characterized by a clinical disorder of sugar and fat metabolism caused by cellular insulin resistance. In our study, the anti-diabetic effects of water extract of Rehmannia glutinosa Libosch (RG) root (40, 200, 1,000 μg/mL) were investigated in mature 3T3-L1 adipocytes. RG root was found to increase glucose uptake under insulin (1 μM)-stimulation conditions but had no effects on glucose uptake without insulin in 3T3-L1 adipocytes. Additionally, the anti-diabetic effects of RG root were studied in a diabetes mellitus animal model (C57BL/KsJ-db/db) by oral ingestion of RG for 4 weeks (50, 500 mg/kg bw/d). During the experimental period, food intake, body weight, and fasting blood glucose level were measured every week. At the end of the treatment, oral glucose tolerance, blood glucose level, HbA1c, plasma insulin level, and blood profile parameters, including AST, ALT, TG, total and HDL-cholesterol levels, were measured. Treatment with RG root resulted in a lower blood glucose level, HbA1c, total cholesterol, ALT, oral glucose tolerance, and serum insulin levels. The mRNA expression of glucokinase (GCK) and solute carrier family 2 (SLC2A2) was significantly increased in liver tissue were reduced by water extract of RG. These results explains the anti-type 2 diabetic effects of water extract of RG.
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김영원 ( Young Won Kim ),민정란 ( Jeong Ran Min ),정진희 ( Jin Hee Jeong ),정상희 ( Sang Hee Jeong ) 한국동물실험대체법학회 2012 동물실험대체법학회지 Vol.6 No.1
Developmental toxicity is one of very important chemical toxicities, which is induced by the exposure of chemicals during embryonic or fetal stages and results in fatal defects of morphology or functions of the offspring. Until now, developmental toxicity test methods are based on laboratory animals or in vitrocultured animal-derived cells or organs. They are relatively expensive and take long time for test and do not sufficiently reflect the real impacts on humans. Therefore, in vitro models based on human embryonic stem cells (hPSCs) have become introduced as an alternative method for developmental toxicity test. We investigated and summarized the key points of the alternative developmental toxicity test methods using human embryonic stem cells. Molecular markers representing differentiation of specific organs or development of critical functions and optimal time for the test of differentiation are suggested. With respect to embryotoxicology, control compounds that mirror strong, weak or none teratogenicity were surveyed to be used in developmental toxicity test to get more accuracy of estimation for real human teratogens. The use of human embryonic stem cells can be regarded as one of future challenges for more precise and efficient models to predict human teratogens.
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연구논문 : In Silico QSAR를 이용한 식품유래 신경발달독성물질 검색 및 독성강도평가ㅂ
정연화 ( Yeon Hwa Jung ),김영원 ( Young Won Kim ),민정란 ( Jeong Ran Min ),정상희 ( Sang Hee Jeong ) 한국동물실험대체법학회 2011 동물실험대체법학회지 Vol.5 No.1
Developmental neurotoxicity (DNT) of chemicals is a serious threat to human health. Exposure to DNT during the perinatal period can result in behavioral abnormalities and cognitive deficits that appear later in life. The aims of this study were to predict human health impact of chemicals via food ingestion using chemical structure-based toxicity predicting program (In Silico QSAR). The determination factors that affect DNT risk potency were selected as developmental toxicity potential (DTP), blood-brain-barrier transfer, a predictor of logarithm of n-octanol/water partition coefficient (VLOGP),rat oral LD50, and rat chronic oral lowest-observed-adverse effect level (LOAEL). 39 kinds of chemicals were identified as high DNT potential chemicals. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and hexachlorobenzene are classified as high DNT potential chemicals. Those chemicals need to be carefully treated as probable high potent DNTs and full scaled in vivo studies are required to characterize the risk of DNT.
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In Silico QSAR를 이용한 식품유래 신경발달독성물질 검색 및 독성강도평가ㅂ
정연화 ( Yeon Hwa Jung ),김영원 ( Young Won Kim ),민정란 ( Jeong Ran Min ),정상희 ( Sang Hee Jeong ) 한국동물실험대체법학회 2011 동물실험대체법학회지 Vol.5 No.1
Developmental neurotoxicity (DNT) of chemicals is a serious threat to human health. Exposure to DNT during the perinatal period can result in behavioral abnormalities and cognitive deficits that appear later in life. The aims of this study were to predict human health impact of chemicals via food ingestion using chemical structure-based toxicity predicting program (In Silico QSAR). The determination factors that affect DNT risk potency were selected as developmental toxicity potential (DTP), blood-brain-barrier transfer, a predictor of logarithm of n-octanol/water partition coefficient (VLOGP),rat oral LD50, and rat chronic oral lowest-observed-adverse effect level (LOAEL). 39 kinds of chemicals were identified as high DNT potential chemicals. 2,3,7,8-Tetrachlorodibenzo-p-dioxin and hexachlorobenzene are classified as high DNT potential chemicals. Those chemicals need to be carefully treated as probable high potent DNTs and full scaled in vivo studies are required to characterize the risk of DNT.
ScienceON
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