• Advances in Traditional Medicine
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• 제5권1호
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• pp.1-15
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• 2005

Ginseng is a popular medicinal plant highly valued throughout the world. Asian ginseng is one of the most common species of ginseng. It has long occupied a significant position in oriental medicine and has been justified its name as the 'king herb'. As a nutritional supplement, ginseng is an extremely common and popular herbal medicine in the United States and Canada in recent decades. The multiple constituents of ginseng possess equally multifaceted pharmacological actions as demonstrated by numerous studies. Ginseng root and its constituents influenced the central nervous system, endocrine, cardiovascular, gastrointestinal system, sexual, renal organ and immune system, etc. One important action is its anti-hyperglycemic effect. Previous studies on ginseng demonstrate that only the root of ginseng has been used in the treatment of diabetes, while the other parts of ginseng plant were always neglected. Recently, we analyzed the constituents of ginseng berry, leaf and discovered that ginseng berry, leaf extracts and its total ginsenosides have the ability to reduce hyperglycemia and body weight and increase the peripheral glucose utilization in obese or diabetic ob/ob or db/db mice. Our data suggest that all parts of ginseng plant, including root, berry, leaf and stem exhibit potent anti-hyperglycemic and anti-obese effects and may provide an opportunity to develop a novel class of anti-diabetic agents.

• 대한한의학방제학회지
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• 제21권1호
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• pp.119-130
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• 2013

Objectives : Diabetes mellitus is the leading cause for vascular complications such as atherosclerosis. The present study is to investigate whether Doinseunggi-tang (DST) improves diabetic vascular dysfunction in type II diabetes. Methods : The db/db mice were treated with high fat/high cholesterol diet and DST (200 mg/kg/day) for 8 weeks. Results : DST significantly lowered blood glucose and systolic blood pressure. In addition, DST also markedly decreased total plasma cholesterol, triglyceride, and LDL-cholesterol, whereas increased the HDL-cholesterol. Vascular relaxation of aortic rings by acetylcholine or SNP was ameliorated by DST in a dose-dependent manner. Damage of vascular intima and hypertrophic of media was improved by DST. Immunohistological study revealed that DST attenuated the increase of ICAM-1, VCAM-1, and ET-1 expression in thoracic aorta. Conclusions : Taken together, DST suppressed hyperglycemia and diabetic vascular dysfunction in type II db/db mice. The present data suggests that Doinseunggi-tang may be prevent a development of diabetic atherosclerosis.

• Biomolecules & Therapeutics
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• 제22권5호
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• pp.445-452
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• 2014

The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.

• 대한한의학회지
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• 제38권2호
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• pp.7-14
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• 2017

Objectives: This study evaluated the effect of aqueous extract from roots of Siberian ginseng on mTORC1 pathway. Methods: mTORC1 activity was measured by the phosphorylation status of p70 S6 kinase (S6K) in HeLa cells as well as the brain, liver and muscle tissues in diabetic db/db mice. Autophagy induction after the treatment of Siberian ginseng extract was evaluated by monitoring the conversion of cytoplasmic LC3I into lipidated LC3II in cultured human HeLa GFP-LC3 cells. Cell cycle analysis was performed in HeLa cells treated with Siberian ginseng using flow cytometry. Results: Among >2,800 plant products used for oriental medicine, Siberian ginseng was found to inhibit mTORC1 to phosphorylate S6 kinsase (S6K) in HeLa cells as well as the brain, liver and muscle tissues in diabetic db/db mice. Siberian ginseng-mediated mTORC1 activity was reversible unlike the prolonged suppression of mTORC1 by rapamycin when HeLa cells were grown in fresh media after the removal of the inhibitors. Siberian ginseng extract at concentrations to inhibit mTORC1 was not overly cytotoxic in cultured HeLa cells whereas rapamycin was obviously cytotoxic. The conversion of cytoplasmic LCI into lipidated LCII was increased by fivefold in HeLa GFP-LC3 cells treated with Siberian ginseng extract. Progression of cell cycle was attenuated at G2/M phase by the treatment of Siberian ginseng extract. Conclusions: These results suggest that the aqueous extract of Siberian ginseng possibly plays a good therapeutic role in various diseases involving mTORC1 signaling.

• Biomolecules & Therapeutics
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• 제21권1호
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• pp.84-88
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• 2013

High risk of cardiovascular diseases caused by existing PPAR-${\gamma}$ agonists such as rosiglitazone and pioglitazone has been recently reported. CKD-501 is a novel selective PPAR-${\gamma}$ agonist as a potential target to reduce cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM). In this study, We investigated potential cardiotoxicity of CKD-501 and compared its toxicity with that of rosiglitazone or pioglitazone using db/db mice. After 12-week repeated administration of CKD-501 at doses of 3, 10 and 30 mg/kg/day or rosiglitazone at doses of 10 and 30 mg/kg/day or pioglitazone at doses of 200 and 540 mg/kg/day, animals were sacrificed for investigation of potential toxicities. Diameters of left ventricles and areas of cardiomyocytes were measured. And lipid accumulation and apoptosis in heart muscle were examined by oil red O staining and TUNEL staining, respectively. Diameters of left ventricles were significantly increased in high dose treatment group of pioglitazone compared to control (p<0.05), while other groups showed a tendency for an increase. All test articles induced significantly the increase of area of cardiomyocytes in heart compared to control (p<0.01), in regular order as pioglitazone > CKD-501 ${\geq}$ rosiglitazone. However, lipid accumulation and apoptotic changes in heart were not observed in all dosing groups. Taken together, the myocardial cell hypertrophy of CKD-501 are relatively lower than that of pioglitazone and similar to rosiglitazone. And it is suggested that the myocardial cell hypertrophy of CKD-501 are less adverse in clinical use for the management of the NIDDM.

• Journal of Microbiology and Biotechnology
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• 제28권8호
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• pp.1247-1259
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• 2018

Raspberries are polyphenol-rich fruits with the potential to reduce the severity of the clinical signs associated with obesity, a phenomenon that may be related to changes in the gut microbiota. The aim of this study was to investigate the effect of raspberry supplementation on the fecal microbiota using an in vivo model of obesity. Obese diabetic db/db mice were used in this study and assigned to two experimental groups (with and without raspberry supplementation). Fecal samples were collected at the end of the supplementation period (8 weeks) and used for bacterial 16S rRNA gene profiling using a MiSeq instrument (Illumina). QIIME 1.8 was used to analyze the 16S data. Raspberry supplementation was associated with an increased abundance of Lachnospiraceae (p = 0.009), a very important group for gut health, and decreased abundances of Lactobacillus, Odoribacter, and the fiber degrader S24-7 family as well as unknown groups of Bacteroidales and Enterobacteriaceae (p < 0.05). These changes were enough to clearly differentiate bacterial communities accordingly to treatment, based on the analysis of UniFrac distance metrics. However, a predictive approach of functional profiles showed no difference between the treatment groups. Fecal metabolomic analysis provided critical information regarding the raspberry-supplemented group, whose relatively higher phytosterol concentrations may be relevant for the host health, considering the proven health benefits of these phytochemicals. Further studies are needed to investigate whether the observed differences in microbial communities (e.g., Lachnospiraceae) or metabolites relate to clinically significant differences that can prompt the use of raspberry extracts to help patients with obesity.

• 한국응용과학기술학회지
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• 제35권4호
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• pp.1369-1378
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• 2018

홍어 껍질 유래 콜라겐 펩타이드를 한외여과막을 이용하여 분자량의 크기를 1,000 Da 이하와 1,000 Da 이상으로 분리하고 그 효과를 비교하고자 하였다. 각각의 시료를 비만 유발 실험동물인 db/db mice에 체중당 200 mg의 콜라겐 펩타이드를 8주간 투여하였다. 본 연구의 결과는 콜라겐 펩타이드를 투여한 군에서 비만대조군에 비해 체중 증가량의 감소, 혈액 및 간조직의 활성산소 농도의 감소, 간조직의 산화적 스트레스가 완화된 것으로 나타났다. 또한 콜라겐 투여군에서 염증반응과 관련된 간조직의 핵전사인자($NF-{\kappa}B$) 및 효소(COX2, iNOS), 염증성 사이토카인(IL-6)발현이 비만대조군에 비해 유의적으로 감소하였다. 분자량의 크기에 따라 약간의 차이가 나타났지만, 전반적으로는 유의적이지 않았다. 따라서 홍어 콜라겐 펩타이드의 비만에 의해 유발된 염증반응이 억제되었는데, 이는 콜라겐의 산화적 스트레스 완화작용에 기인한 것으로 사료된다.

• 한국식생활문화학회지
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• 제23권5호
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• pp.662-665
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• 2008

Takju lees extract is expected to be a promising material for functional food. This study was conducted in order to assess the glycemic index (GI) of Takju lees extract and its effects in an oral glucose tolerance test (OGTT). The GI for Takju lees extract was evaluated with 10 healthy young adults (Male 5, Female 5). OGTT was conducted in 20 male db/db mice, fed on a diet containing 2% Takju lees extract for 4 weeks. Those animals were subjected to OGTT after one oral administration of Takju lees extract at 2 g/kg BW. The GI of the Takju lees extract was measured at 97.97. The effects of the Takju lees extract on the oral glucose tolerance test in db/db mice evidenced no differences as compared to the control group. In conclusion, Takju lees extract is a high GI material, and it has no effect on blood glucose levels in a type II diabetic animal model. Further studies will be required to confirm its anti-diabetic effects.

• 한국식품영양과학회지
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• 제41권3호
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• pp.339-344
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• 2012

본 연구에서는 제2형 당뇨병 모델인 C57BLKS/J-db/db 마우스에서 발아일품벼 추출물의 농도별로 급여한 후 혈당 조절에 미치는 영향을 알아보고자 조사하였다. C57BLKS/J-db/db 마우스에게 급여한 발아일품벼 추출물의 양에 따라 5군 즉, 정상군(Normal Control: NC), 당뇨대조군(Diabetic Control: DC), 1% 발아벼 추출물 급여군(DM-1% GIRRE), 0.5% 발아벼 추출물 급여군(DM-0.5%GIRRE), 0.25% 발아벼 추출물 급여군(DM-0.25%GIRRE)으로 나누었다. 8주 동안 매일 식이 섭취량과 음료섭취량 및 매주 체중과 공복혈당을 측정하고 마지막 주에 경구포도당 부하검사(OGTT)를 실시하였으며, 부검 시 혈액을 채취하여 혈청인슐린 농도와 당화혈색소를 측정하였다. 그 결과, DM-1% GIRRE군에서 당뇨유발에 의한 체중감소 및 당뇨 증상 중에 다음(poly-dipsia), 다식(polyphasia) 등이 어느 정도 완화되고 있음을 알 수 있다. DM-1%GIRRE군에서 당뇨동물의 공복 혈당, 경구 내당능 검사, 혈중 HbA1c 수준을 유의적으로 낮추었지만, 혈장 인슐린 농도는 당뇨실험군들 간에는 차이가 나타나지 않았다. 이상의 결과를 종합해보면 발아일품벼추출물의 급여가 혈당상승을 억제하는 효과가 있는 것으로 생각되며 그 기전에 대해서는 향후 추가 연구가 필요하다고 본다.

• 한국식품위생안전성학회지
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• 제24권4호
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• pp.391-397
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• 2009

당뇨는 비정상적 인슐린의 작용으로 고혈당상태에 이르게 되는 내분비계 질환으로서, 다양한 합병증을 야기는 질환이다. carnosine은 $\beta$-alanine과 L-histidine으로 이루어진 dipeptide로서 생체내 여러 조직에 널리 분포하고 있고, 항노화, 항산화 기능을 가지는 것으로 알려져 있다. 본 연구에서는 제2형 C57BL/6J db/db mice모델을 사용하여 8주 동안 carnosine 투여 후 carnsoine의 항당뇨 효과를 보았다. 실험군은 총 5개로 정상군, 대조군, carnosine 6, 30, 150 mg/kg 투여군으로 설정하였다. 혈당조절정도를 마우스의 정맥혈에서 혈당측정기를 이용하여 측정하였고, 포도당 내성 검사를 통해 시험물질의 포도당 의존성을 보았고, 또한 혈청내의 생화학적수치와 지질학적수치 등을 측정하여 증감의 정도를 측정하였다. 결과로서, carnosine 투여는 8주후 혈당을 유의적으로 감소시켰으며(p < 0.05), 혈당내성 검사 및 인슐린내성검사에서도 유의적으로 혈당치를 낮추었다(p < 0.05), 혈중 인슐린 량은 carnsoine 투여군 모두에서 낮게 나타났으나, 특히 저농도에서 유의적으로 낮았다 (p < 0.05). 혈액생화학적 수치에서는 carnosine 투여 군이 대조군보다 총단백질 수치가 높았으며, LDH 및 BUN 수치는 낮게 나타났다. 혈액 지질수치에서도 carnosine투여는 glucose 농도를 유의적으로 감소시켰으며, 더불어 LDL 수치를 낮췄으나, HDL 수치에는 변화가 없었다. 결론적으로 carnosine은 제2형 마우스모델에서 농도 비의존적 항당뇨 효과를 나타내었으나, carnosine는 생체내 항산화 및 항노화 효과와 더불어 항당뇨 효과를 갖는 것으로 사료된다.