• 한국미생물·생명공학회지
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• 제44권2호
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• pp.124-129
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• 2016

식용버섯인 노랑느타리버섯으로부터 α-glucosidase 저해제의 추출과 정제에 대하여 연구하였다. α-glucosidase 저해제는 노랑느타리버섯 자실체를 증류수로 30℃에서 12시간 처리하였을 때 가장 많이 추출되었다. α-glucosidase 저해제를 sephadex G-100 여과 크로마토그래피와 펩신 가수분해, sephadex G-50 여과 크로마토그래피, 역상 HPLC로 정제한 결과 수율과 α-glucosidase 저해활성은 각각 12.2%와 IC₅₀ 9.10 mg/ml이었다. 정제한 α-glucosidase 저해제는 Thr-Ile-Ala-Phe-Ile-Asp (A)과 Tyr-Tyr-Ala-Ile-Gly-Asp (B)의 서열을 갖고 있는 두개의 헥사펩타이드를 함유하였고 이들의 분자량은 각각 (A)가 678.79 Da, (B)가 643.7 Da이었다. 정제한 α-glucosidase 저해제는 α-glucosidase에 대하여 혼합형 저해양상을 보였고 streptozotocin으로 유도된 당뇨 쥐모델에서 50 mg/kg과 300 mg/kg 투여시 혈당함량을 낮추어 주는, 농도 의존적 혈당상승억제 효과를 보였다.

• 고려인삼학회:학술대회논문집
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• 고려인삼학회 2002년도 학술대회지
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• pp.129-144
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• 2002

We investigated anti-hyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic C57BL/6J ob/ob mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract for 12 days. On Day 5, 150 mg/kg extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to vehicle-treated mice $(156{\pm}9.0\;mg/dl\;vs.\;243{\pm}15.8mg/dl,$ P<0.01). On Day 12, the extract-treated ob/ob mice became normoglycemic $(137{\pm}6.7\;mg/dl)$ and had significantly improved glucose tolerance. The overall glucose excursion during the two-hour intraperitoneal glucose tolerance test (IPGTT), calculated as area under the curve (AUC), decreased by $46\%$ (P<0.01) compared to vehicle-treated ob/ob mice. Glucose levels of lean mice were not significantly affected by the extract. The improvement in blood glucose levels in 150 mg/kg extracttreated ob/ob mice was associated with significant reduction in serum insulin levels of fed and fasting mice. Consistent with an improvement in insulin sensitivity, hyperinsulinemic euglycemic clamp study revealed a more than 2-fold increase in the rate of insulin-stimulated glucose disposal in treated ob/ob mice $(112{\pm}19.1\;vs.\;52{\pm}11.8{\mu}mol/kg/min$ for the vehicle group, P<0.01). In addition, 150 mg/kg extract-treated ob/ob mice, but not the lean mice, lost significant weight (from $51.7{\pm}1.9g\;on\;Day\;0\;to\;45.7{\pm}1.2$ on Day 12, P<0.01 compared to vehicle-treated ob/ob mice), associated with a significant reduction in food intake (P<0.05) and a very significant increase in energy expenditure (P<0.01) and body temperature (P<0.01). A 12-day treatment with 150 mg/kg Panax ginseng berry extract also significantly reduced plasma cholesterol levels in ob/ob mice. Additional studies demonstrated that ginsenoside Re, a major constituent of the ginseng berry, but not from the root, plays a significant role in anti-hyperglycemic action. This anti-diabetic effect of ginsenoside Re was not associated with body weight changes, suggesting that other constituents in the extract have distinct pharmacological mechanisms on energy metabolism. The identification of a significant anti-hyperglycemic activity in ginsenoside Re may provide an opportunity to develop a novel class of anti-diabetic agent.

• 생약학회지
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• 제42권2호
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• pp.201-208
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• 2011

Obesity occur from the imbalance between energy intake and energy expenditure. Obesity is a complex chronic disease that is suggested to cause other metabolic disorders such as type 2 diabetes, hyperlipidemia, hypertension, and arteriosclerosis. In this study, our purpose is to investigate the anti-hyperglycemic and anti-obesitic effects of Maydis stigma water extract in 3T3-L1 adipocytes and db/db mice. Maydis stigma water extract at dose of 100 and 500 ${\mu}g/ml$ slowly inhibited cell viability as compared to that of control in mature adipocytes. Also, the additions of 50 and 250 ${\mu}g/ml$ of Maydis stigma water extract significantly inhibited the lipid accumulations and CCAAT/enhancer-binding protein(C/EBP) ${\alpha}$ and peroxisome proliferator-activated receptor(PPAR) ${\gamma}$ expressions with dose-dependent manner in 3T3-L1 adipocytes. Maydis stigma water extract at 250, 500, and 1000 ${\mu}g/ml$ only showed the increasing pattern on lipolysis activity. The oral treatment of Maydis stigma water extract (100 or 400 mg/kg body weight) in db/db mice only showed tendency to decrease body weight, food efficiency ratio (FER), HbA1c, blood glucose, total cholesterol, triglyceride, and the adipocyte size of in db/db mice. However, Maydis stigma water extract increased the insulin level in a dose dependent manner. Thus these results indicate that Maydis stigma water extracxt inhibits adipogenesis through regulation of C/EBP${\alpha}$ and PPAR${\gamma}$ expressions in 3T3-L1 adipocytes and shows anti-hyperglycemic effect through increase of insulin secretion in db/db mice.

• 한국식품과학회지
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• 제32권6호
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• pp.1418-1425
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• 2000

아가리쿠스 버섯(동결 건조, 온풍 건조)에서 추출한 ${\beta}-glucan$을 7주령의 db/db마우스에 5주간 음용수로 제공하고 식이섭취량 및 체중의 변화를 관찰하고 혈액내의 포도당, 인슐린, 당화 헤모글로빈, 소장의 glycosidase의 활성을 측정하고 중성지방농도, 혈중 지질조성을 측정하였으며 결과는 다음과 같다. db/db 마우스에서 Agari.F군과 Agari.H군은 식이섭취량에서 Control군보다 유의적으로 낮았고, 그에 따라 체중증가량도 낮았으며, 혈중 인슐린 농도와 당화헤모글로빈 농도는 Control군에 비해 Agari.F군, Agari.H군, Acarbose군이 유의적으로 낮은 수준이었다. 소장의 maltase, lactase, sucrase의 활성은 Control군에서 Lean군에 비해 세 효소의 활성이 매우 높게 관찰되었고, 시료투여군인 Agari.F군, Agari.H군은 maltase의 경우 proximal, middle 부위는 대조군보다 낮았고 distal 부위에서는 Agari.F군의 활성이 가장 높았다. Sucrase, lactase의 활성은 모든 부위에서 시료투여군이 Control군보다 낮은 수준이었다. 혈중 중성지방 농도는 Control군에 비해 Agari.F군, Agari.H군, Acarbose군은 유의적으로 낮은 수준이었다. 혈중 total cholesterol의 농도의 경우 Control군과 Agari.H군은 유의적인 차이가 없었지만 Agari.F군과 Acarbose군은 유의적으로 낮았다. 혈중 VLDL cholesterol의 경우는 Control군에 비해 Agari.F군, Agari.H군은 유의적으로 낮았고 Acarbose군은 유의적인 차이가 없었다. 혈중 LDL cholesterol의 농도는 Control군이 유의적으로 높았으며, Acarbose군이 가장 낮았다. 혈중 HDL cholesterol의 농도는 Agari.H군이 유의적으로 가장 높았고, Control군이 가장 낮았다.

• Advances in Traditional Medicine
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• 제8권4호
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• pp.349-353
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• 2008

Anti-diabetic effect was observed with Thespesia lampas Dalz & Gibs (Family: Malvaceae) when given as a root extract in normal as well as alloxan induced diabetic rats. The effects, however, were more pronounced in diabetic animals in which administration of plant extract for 15 days after alloxan induced diabetes, significantly reduced blood glucose levels. After alloxan induced diabetes it was observed that both standard drug (glibenclamide) and aqueous extract of Thespesia lampas were significantly superior to control in reducing blood sugar on long term treatment (15 days). The aqueous extract of T. lampas (300 and 600 mg/kg) reduced the blood glucose levels from $349.2{\pm}7.2$ to $120.7{\pm}4.6$ and $346.3{\pm}3.4$ to $101.8{\pm}6.3$, respectively. The data suggested that T. lampas could be of beneficial in diabetes mellitus in controlling blood sugar. The present investigation established pharmacological evidence to support the folklore claim as an anti-diabetic.

• 생약학회지
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• 제38권1호
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• pp.10-14
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• 2007

Type 2 diabetes mellitus relavant to insulin resistance is a chronic and hard to control. In order to develop an antidiabetic agent from natural products, anti-hyperglycemic effect of herbal formula containing Mori Follium, Euonymi Lignum Suberalatum and Ginseng Radix(MEG) was investigated in db/db mice. Treatment group was administered orally with MEG formula at a dose of 300 mg/kg for 5 weeks, and blood glucose, insulin and lipid levels were determined. MEG treatment group showed a marked decrease in fasting blood glucose level and insulin resistance index(IRI) compared to those in diabetic control. Improvement of insulin resistance(60.6%) was indicative of reducing lipid levels in plasma and triglyceride contents in muscle and adipose tissue. In addition, expressions of an insulin responsive gene, glucose transporter 4(Glut4), in muscle and adipose tissue were upregulated in MEG treatment group. Compared islet morphology between groups, MEG formula prevented the ${\beta}$-cell destruction caused by high blood glucose. Taken together, MEG formula can act as an anti-hyperglycemic agent with insulin sensitizing effect, and thus deserves a clinical trial in the future.

• Preventive Nutrition and Food Science
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• 제20권2호
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• pp.94-101
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• 2015

Grape products have been known to exert greater antioxidant and anti-obesity than anti-hyperglycemic effects in animals and humans. Omija is used as an ingredient in traditional medicine, and it is known to have an anti-hyperglycemic effect. We investigated whether the combined extracts of grape pomace and omija fruit (GE+OE) could reduce fat accumulation in adipose and hepatic tissues and provide beneficial effects against hyperglycemia and insulin resistance in type 2 diabetic mice. C57BL/KsJ-db/db mice were fed either a normal control diet or GE+OE (0.5% grape pomace extract and 0.05% omija fruit extract, w/w) for 7 weeks. GE+OE decreased plasma leptin and resistin levels while increasing adiponectin levels and reducing the total white adipose tissue weight. Furthermore, GE+OE lowered plasma free fatty acid (FFA), triglyceride, and total-cholesterol levels as well as hepatic FFA and cholesterol levels. Hepatic fatty acid synthase and glucose 6-phosphate dehydrogenase activities were decreased in the GE+OE group, whereas hepatic ${\beta}$-oxidation activity was increased. Furthermore, GE+OE supplementation not only reduced hyperglycemia and pancreatic ${\beta}$-cell failure but also lowered blood glycosylated hemoglobin and plasma insulin levels. The homeostasis model assessment of insulin resistance levels was also decreased and the decrease seems to be mediated by the lowered activities of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinases. The present data suggest that GE+OE may have the potential to reduce hyperglycemia, insulin resistance, and obesity in patients with type 2 diabetes.

• Applied Biological Chemistry
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• 제48권1호
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• pp.103-108
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• 2005

${\alpha}-Amylase$ 저해제는 소장에서 전분의 소화를 저해하여 포도당의 흡수를 지연시킴으로써 혈당 조절 목적으로 이용된다. 따라서 본 연구에서는 ${\alpha}-amylase$ 저해제를 탐색할 목적으로 국내 자생 목본류 약 1400여종의 70% ethanol 추출액을 대상으로 ${\alpha}-amylase$ 저해제 분포를 검색하였다. 수종의 목본류에서 ${\alpha}-amylase$ 저해제가 분포하고 있음이 확인되었으며, 그 중 활성이 비교적 높은 말채나무 기원의 저해제를 대상으로 연구를 진행하였다. 기원별 효소에 따른 저해 활성도를 살펴보면 salivary와 pancreatic ${\alpha}-amylase$, 미생물 기원의 ${\alpha}-glucosidase$에는 탁월한 저해 활성을 보인 반면 돼지 기원의 ${\alpha}-glucosidase$ 저해제에 대해서는 매우 낮은 저해 활성을 보였다. ${\alpha}-Amylase$와 ${\alpha}-glucosidase$의 kinetic을 분석하면 salivary와 pancreatic 두 효소에 모두 경쟁적 저해제로, 효모의 ${\alpha}-glucosidase$에는 비경쟁적과 반경쟁적의 혼합형 저해제로 나타났다. 또한 열과 산성에 대한 안정성을 확인한 결과 비교적 안정적인 것으로 나타났다. 본 추출물의 식이 섭취에 따른 혈당 강하 효과와 체중에 미치는 영향에서는 혈당과 체중 상승을 억제하는 효과가 확인되었고, mRNA수준에서 대퇴근 세포에 있어서 GLUT4의 발현이 증가됨을 확인하였다.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2002년도 창립10주년기념 및 국립독성연구원 의약품동등성평가부서 신설기념 국재학술대회:생물학적 동등성과 의약품 개발 전략을 위한 국제심포지움
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• pp.219-219
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• 2002

The SPP003 is a mixture of water extract from Schizandrae Fructus, Poligoni multiflori Radix, Ginseng Radix Akba and Hoelen. The aim of this study was to investigate the anti-hyperglycemic effect of SPP003 in normal and streptozotocin (STZ)-induced diabetic rats, and to monitor the toxicity of SPP003. Oral glucose tolerance test (OGTT) was performed after oral administration of SPP003 100, 300, 600 and 900 mg/kg in normal rats. Blood glucese concentration was measured at -30 min (vehicle, SPP003 or tolbutamide 60 mg/kg, 0 min (glucose treatment), 60, 120 and 180 min. Rats were administerd STZ 65mg/kg (0.1M citrate buffer, pH 4.5) intraperitoneally to induce diabetes and administered vehicle, Spp003 (100, 300 and 600 mg/kg) or tolbutamide (60 mg/kg) orally once a day for 4 weeks. Blood glucose level was measured a 0, 4, 7, 14, 21 and 29 day after initial drug administration. A single oral toxicity of SPP003 was studied in Sprague-Dawley rats of both sexes. In this study, rats were administered with doses of 1, 2 and 5 g/kg of SPP003. In glucose tolerance test, SPP003 900 mg/kg markedly decreased glucose concentration at 1 hr after glucose treatment. Blood glucose levels were much higher in STZ-diabetic rats. These increases were significantly attenuated by SPP003 600 mg/kg. SPP003 did not show any signigicant toxicity. These findings suggest that SPP003 has hypoglycemic properties in STZ-diabetic rats.

• 한국식품과학회지
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• 제31권4호
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• pp.1057-1064
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• 1999

8주령의 C57BL/KsJ db/db마우스에 상백피 냉침추출물을 투여하면서 5주간 사육하여 식이섭취량, 체중변화, 혈중 포도당 농도를 관찰하고, 소장내 ${\alpha}-glycosidase$ 활성변화와 혈중 당화헤모글로빈 농도, 중성지방 농도, 인슐린 농도를 측정하였다. 상백피추출물 500 mg/kg을 공급하는 Rad 500군과 1000 mg/kg을 공급하는 Rad 1000군, db/db 대조군과 lean군으로 나누고 대조약물로는 acarbose 5 mg/kg을 투여하였다. Rad 1000군은 식이섭취량에서 db/db 대조군보다 낮은 수준이었으며 그에 따라 체중증가량도 유의적으로 낮았다. 또한 공복시 혈중포도당 농도는 Rad 500, Rad 1000, acarbose군 모두 db/db 대조군보다 낮았다. 혈중 당화헤모글로빈 농도와 중성지방 함량 측정결과는 농도의존적으로 시료투여군이 db/db대조군보다 낮게 측정되었다. 혈중 인슐린 농도 측정결과 lean군을 제외한 나머지군간에 유의적인 차이는 없었고 Rad 500군에서 약간 높은 수준이 관찰되었다. 소장을 proximal, middle, distal 세부위로 나누어 각각에 대해 maltase, sucrase, lactase의 활성을 측정해본 결과 db/db군은 lean군에 비해 세효소의 활성이 매우 높은 활성을 나타내었으며, 시료투여군은 sucrase의 경우 proximal, middle 부위는 db/db군 보다 낮고 distal 부위는 활성이 높았다. Maltase, lactase의 활성은 모든부위에서 시료투여군이 db/db군 보다 낮아 lean군 수준이었다. 이상의 결과들로 미루어 상백피는 db/db마우스에서 식이섭취량을 줄여주어 체중증가를 억제시키고 소장내 glycosidase활성을 전반적으로 낮춰 혈중포도당 농도를 낮춰주고 혈중 당화헤모글로빈 농도와 중성지방 농도를 낮춰주는 등의 항당뇨효과가 있음을 알 수 있었다.