• Journal of Pharmaceutical Investigation
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• 제33권2호
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• pp.113-120
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• 2003

Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alternations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of micovascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. The purpose of this study was to investigate thε effect of Laminaria japonica diet on the absorption, distribution, metabolism and excretion of glipizide which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agents were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as $k_{a},\;t_{1/2},\;C_{max},\;t_{max}$ and AUC. Administration of glipizide in normal rats treated with Laminaria japonica diet showed significant increase in AUC, $k_{a},\;t_{1/2},\;t_{max}$ and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption. Administration of glipizide in diabetic rats treated with Laminaria japonica diet showed significant increase in $t_{1/2}\;and\;t_{max}$, and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might also result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption and flattened blood concentration of glipizide. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of glipizide caused by long-term Laminaria japonica diet.

• Journal of Nutrition and Health
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• 제35권1호
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• pp.5-14
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• 2002

Alteration in the syntesis or enhanced inactivation of nitric oxide(NO) can induce impairment of endothelial cell function. Insulin dependent diabetes mellitus(IDDM) is characterized by impaired endothelial function and vascular disease. NO is produced through L-arginine pathway To elucidate the hypothesis that the decreased production on NO in IDDM reflects vascular damage and the NO production can be manipulated by either dietary fat(7% of kg diet) or the oral supplementation with L-arginine(2g/kg bw), plasma markers for vascular endothelial damage and plasma lipid profiles were measured in streptozotocin(STZ)-induced diabetic rats. Diabetic or normal Sprague-Dawley rats were fed 6 different experimental diets for 4 weeks(SO : soybean oil, SOA: soybean oil + L-arginine supplementation, BT : beef tallow, BTA_ beef tallow + L-arginine supplementation, OV olive oil, OVA : olive oil + L-arginine supplementation). Plasma glucose, total cholesterel, HDL-cholesterol, LDL-cholesterol and triglyceride were measured. Endothelial markers, plasma von Willebrand factor(vWf), thromboxane B$_2$, and 6-keto PGF1$\alpha$ of aorta were measured by ELISA. Plasma NO production was evaluated through the measurement of nitrite by EIA. Feeding saturated fatty acid(SFA, BT) increased relative liver size(RLS) in diabetic rats compared to either polyunsatunted fatty acid(PUFA, SO) or monounsaturated fatty acid(MUFA, OV) The supplementation of L-arginine inhibited the liver and kidney enlargement in olive oil find diabetic rats. Plasma glucose was lower in diabetic animal find the olive oil compared to fed beef tallow and the supplementation L-arginine decreased it in diabetic rats find beef tallow significantly(p < 0.05). Plasma TXB$_2$ levels were increased due to diabetes and the value of beef tallow group showed highest value. Plasma vWf concentration of beef tallow group was higher value in normal rats and was elevated more in diabetes. In diabetic groups, the vWf concentration of olive oil group was lower than beef tallow or soybean oil group. The supplementation of L-arginine in diabetic rats decreased plasma TXB$_2$ and vWf levels significantly(p < 0.05). NO production was higher in normal olive oil fed rats and was tend to be decreased in diabetic rats and the supplementation of L-arginine recovered to normal value(p < 0.05), Olive oil supplemented with L-arginine tended to lower plasma total cholesterol and LDL-cholesterol after 4 week treatment. These results suggest that generalized vascular endothelial changes based on plasma TXB$_2$and vWf occurs in diabetic rats. and olive oil with L-arginine supplementation contributes to a better control of the hyperglycemia, endothelial changes and hypercholesterolemia accompanying diabetes as compared with beef tallow or soy bean oil in this rat model.

• 한국식품영양과학회지
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• 제28권5호
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• pp.1137-1143
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• 1999

This study investigated the effect of tea fungus/kombucha beverage(TF) protein concentrations and enzyme activities in serum of both normal and diabetic male rats. Sprague Dawley growing rats were randomly assigned to one control and five diabetic groups. In five diabetic groups, D control group was fed drinking water and the other groups were fed drinking water supplemented with 20 or 40% TF (20 or 40% TFD group, respectively) and 20 or 40% disinfected TF(20 or 40% TFSD group, respectively) for 7 weeks. Diabetes was experimentally induced in all five diabetic groups by streptozotocin injection after 3 week feeding. The diabetic groups were significantly decreased the body weight( 29.4~ 48.6g) compared with those in control group(72.4g). The total liver and kidney weights in all diabetic groups were similar to those in control group, but those relative to body weights in all diabetic groups were heavier than those in control group. The total spleen weight in all diabetic groups was significantly decreased compared with those in control group, but those relative to body weights in all diabetic groups were similar to those in control group. The blood glucose levels were heigher in all diabetic groups than those in control group. The alkaline phosphatase activity in serum was higher in all experimental groups than those in control group, but it was lower in 40% TFD, 20% and 40% TFSD groups than those in D control group. The GPT activity was significantly increased in D control, 20% and 40% TFD groups than in control group. The GOT activity was significantly increased in D control goup than in control group, but those in all TFD and TFSD groups were similar to control group. The total protein concentration in all diabetic groups was significantly decreased compared with that in control group, but the albumin concentration showed almost the same levels in all the experimental groups. The ratio of albumin/globulin, and hem atocrit value were significantly increased in all diabetic groups than in control group. These results show that tea fungus/kombucha beverage with which diabetic rats were fed has not recovered the decreased body weight, lowered serum total protein level, hypertrophy of liver and kidney, hyperglycemia to the normal state.

• 동아시아식생활학회지
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• 제18권6호
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• pp.939-948
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• 2008

삼나물 에탄올 추출물이 streptozotocin으로 유발한 쥐의 당뇨증상과 산화적 스트레스에 미치는 영향을 조사하였다. 실험군은 정상군(NC), 당뇨군(DM), 당뇨유발 후 식이에 삼나물 에탄올 추출물을 0.3%를 첨가한 식이군(SA), 당뇨유발 후 식이에 삼나물 에탄올 추출물을 0.6% 첨가한 식이군(SB)으로 구분하여 5주간 사육하였다. SA군과 SB군은 NC군에는 미치지 못하였으나, 당뇨로 인해 초래되는 병리적 증상인 체중 감소, 식이섭취량 및 음용수 섭취량의 증가, 식이효율저하, 간장 및 신장 무게의 증가 현상을 개선하는 효과가 있었다. 실험식이로 5주간 사육한 당뇨쥐의 혈당은 DM군에 비하여 $17.9{\sim}27.2%$를 감소시켰으며 fructosamine의 함량은 $25.6{\sim}32.6%$를 감소시켰다. 또한, 당뇨로 인하여 증가된 alanine aminotransferase(ALT)와 aspartate aminotransferase(AST) 활성을 각각 25.6 및 30.3% 감소시켰다. SA 및 SB군은 DM군에 비하여 혈청 중성지질은 $42.37{\sim}55.51%$ 감소, total cholesterol 함량은 $26.85{\sim}30.44%$ 감소, HDL-cholesterol 함량은 $13.01{\sim}17.35%$ 증가, LDL-cholesterol 함량은 $37.29{\sim}39.11%$가 감소하였다. SA 및 SB군의 xanthine oxidoreductase의 total type, O type 및 O/T(%)은 DM군에 비하여 유의적으로 감소하였으며 간 조직 glutathione함량은 유의적으로 증가 lipid peroxide 함량은 유의적으로 감소시켰다. Superoxide dismutase와 glutathione S-transferase 활성도 DM군에 비하여 각각 $56.84{\sim}94.90%$ 및 $57.14{\sim}68.92%$를 증가시켰다. 이상의 실험 결과 삼나물 에탄을 추출물은 STZ로 유도한 당뇨쥐의 고혈당을 완화시킴과 동시에 ROS 생성계를 억제하고 ROS 소거계를 활성화시킴으로써 당뇨를 경감시키는 효과가 있는 것으로 사료된다.

• 한국식품과학회지
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• 제42권2호
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• pp.204-209
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• 2010

STZ으로 당뇨를 유발 8주 후 당뇨대조군은 공복혈당이 $451{\pm}42.6\;mg/dL$인데 비해 Kocat-D1-1(Kocat-D1 추출물을 0.25 g/kg/day 투여한 군)에서는 $334.3{\pm}32.9\;mg/dL$, Kocat-D1-2(Kocat-D1 추출물을 1 g/kg/day 투여한 군)에서는 $259.5{\pm}35.0\;mg/dL$로 투여 농도에 의존적으로 당뇨대조군에 비해 유의적 수준으로 혈당이 낮아졌다. OGTT 검사에서도 180분 경과 후에도 당뇨대조군은 포도당 투여전보다 혈당이 $55.5{\pm}5.1\;mg/dL$ 높았으나 Kocat-D1-2는 $17.0{\pm}7.4\;mg/dL$로 유의적으로 낮아졌다. STZ에 의해 유도된 당뇨쥐는 정상대조군에 비해 혈장내의 GOT($411.3{\pm}31.3\;U/L$), GPT($162.3{\pm}23.2\;U/L$) 모두 현저히 증가하였다. 이에 비해 Kocat-D1-2 군에서는 GOT($247.0{\pm}33.4\;U/L$), GPT($116.3{\pm}17.4\;U/L$) 모두 유의적인 수준으로 당뇨대조군에 비해 감소하였다. 알부민 수치 또한 정상대조군 $3.9{\pm}0.1\;U/L$에 비해 당뇨대조군은 $2.7{\pm}0.3\;U/L$으로 낮아졌으나 Kocat-D1-2군에서는 $3.0{\pm}0.1\;U/L$로 증가하였다. HDL-콜레스테롤 수치 또한 정상대조군이 $26.8{\pm}3.9\;mg/dL$인데 비해 당뇨대조군은 $11.7{\pm}1.3\;mg/dL$로 낮아졌다. 그러나 Kocat-D1을 투여한 두 군 모두 각각 $22.3{\pm}2.0$, $26.8{\pm}1.2\;mg/dL$로 유의적인 수준으로 증가하였다. 간조직의 조직학적 관찰에서도 당뇨대조군의 경우 간세포사이에 지방구가 관찰되었으나, Kocat-D1-2는 거의 정상대조군과 유사하였으며 지방구를 관찰 할 수 없었다. 각 실험군의 혈액 중 인슐린 농도를 측정한 결과 정상대조군 $0.18{\pm}0.02\;ng/mL$인데 비해 당뇨대조군은 $0.05{\pm}0.04\;ng/mL$로 낮아졌으나 Kocat-D1-1은 $0.11{\pm}0.05$, Kocat-D1-2는 $0.13{\pm}0.02\;ng/mL$로 증가하였다. 췌장의 베타세포의 상대적 용적을 측정한 결과 Kocat-D1-2 군은 당뇨대조군의 $12.9{\pm}7.9%$에 비해 $49.4{\pm}4.2%$로 유의적인 수준으로 증가하였다. Kocat-D1-1군에서도 당뇨대조군보다 증가하는 경향은 보였으나 유의적인 차이는 없었다. Kocat-D1은 인슐린을 분비를 촉진시켜 혈당을 강하시키는 항당뇨효과를 가지고 있음을 알 수 있었다. 따라서 아직 명확한 학명 규명이 규명되지는 않았지만 Kocat-D1은 의약품 소재 및 기능성 식품 소재로서의 활용가능성이 있음을 본 연구를 통해 확인하였다.

• 생약학회지
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• 제47권4호
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• pp.312-318
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• 2016

Advanced glycation end products (AGEs) such as $N^{\varepsilon}$-(carboxy-methyl)lysine (CML) have been implicated in the development of diabetic nephropathy. The aim of this study was to investigate the inhibitory effects of ethanolic extract of Aster koraiensis (AKE) on AGEs formation and AGEs-collagen cross-linking in vitro and CMLs formation in streptozotocin (STZ)-induced diabetic rats. AKE significantly inhibited AGEs formation ($IC_{50}$ value of $18.74{\mu}g/mL$) and AGEs-collagen cross-linking ($IC_{50}$ value of 0.274 mg/mL) in vitro than the well-known glycation inhibitor aminoguanidine ($IC_{50}$ value of $72.12{\mu}g/mL$ and 1.99 mg/mL, respectively). AKE (100 mg/kg per day) was given to diabetic rats for 9 weeks. In STZ-induced diabetic rats, severe hyperglycemia was developed, and urinary CMLs and plasma CMLs were markedly increased. Immunohistochemical stain revealed that CMLs were accumulated within renal glomerulus in STZ-induced diabetic rats. However, AKE significantly reduced urinary CMLs and plasma CMLs in diabetic rats. CMLs accumulation was inhibited by AKE treatment in the renal glomerulus. These results suggest that AKE had an inhibitory effect of AGE accumulation in the glomeruli of diabetic rat and could be an inhibitor of AGE-induced protein cross-linking. The oral administration of AKE may significantly help to prevent the progression of diabetic nephropathy in patients with diabetes.

• 한국인삼전략화협의회:학술대회논문집
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• 한국인삼전략화협의회 2003년도 제4차 한국인삼약초산업 전략화 세미나
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• pp.77-88
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• 2003

"Ginseng (Panax ginseng C.A. Meyer) has been a popular herbal remedy used in eastern Asian cultures for thousands of years, and a number of health claims are made for it. Modern therapeutic claims for ginseng refer to vitality, immune function, cancer, cardiovascular diseases, diabetes and sexual function. These claims are mostly based on uncontrolled or non-randomized studies. Among modern therapeutic claims, however, therapeutic effects for diabetes can reasonably be accepted. Following experiment was done recently in our lab: this study was designed to compare the antidiabetic activities between Ginseng Radix Alba (GRA), Ginseng Radix Rubra (GRR) and Panax Quinquefoli Radix (PQR) in multiple low dose (MLD) streptozotocin (STZ) (20mg/kg i.p injection for 5 days) induced diabetic rats. In the glucose tolerance test, 500mg/kg of each ginseng ethanol extract was admoinistered intraperitoneally 30min before glucose challenge. While GRA failed to lower blood glucose level, GRR and PQR both significantly prevented the hyperglycemia when compared with the control group. In the MLD STZ-induced diabetic rats, 300 mg/kg of each ginseng ethanol extract was administered intraperitoneally for 2 weeks. Plasma glucose and insulin levels were markedly improved in all treatment groups. While GRR showed the highest antidiabetic activity, and GRA and PQR revealed somewhat equipotent antidiabetic activities, but less than that in GRR-treated group as for as blood parameters and diabetic symptoms such as polydipsia are concerned. Blood glucose levels were closely associated with plasma insulin levels, and this result may suggest that ginseng ethanol extracts showed the activity to enhance insulin secretion as well as preventing destruction of pancreatic islet cells. To elucidate the relationship between antidiabetic activity and ginsenoside profiles, seven major ginsenoside were quantified by HPLC. We figured out the fact that protopanaxatriol (PPT) : proptopanaxadiol (PPD) ratio might play an important role in its hypoglycemia effects."

• 약학회지
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• 제55권4호
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• pp.301-308
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• 2011

Diabetes has been one of major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has been focused as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK increases glucose uptake through independent insulin signal pathway. In this study, we investigated the anti-diabetic effect of Angelica gigas Nakai extract (AGNEX), a mixture of decursin and decursinol angelate (53 : 47), decursin and decursinol angelate on blood glucose, glucose transport (GLUT) and AMPK expression levels in streptozotocin (STZ)-induced diabetic rats. To induce diabetes, 50 mg/kg of STZ was injected via i.v. route and AGNEX 2 mg/kg (STZ+AG), decursin 2 mg/kg (STZ+D), decursinol angelate 2 mg/kg (STZ+DA), and metformin 100 mg/kg (STZ+M) were administered orally for 21 days. STZ+DA group showed a significant decrease in fasting blood glucose levels compared to the other groups. Decursinol angelate significantly upregulated expression of glucose transporter 4 (GLUT4) and phosphorylation of AMPK (p-AMPK) in skeletal muscle of rats. In pancreas of rats, decursinol angelate significantly increased expression of GLUT2 through down-regulation of p-AMPK. In addition to the result of pancreatic islets morphology, AGNEX, decursin, decursinol angelate, and metformin treated group recovered ${\beta}$-cell damage by hyperglycemia. These results indicate that decursinol angelate might be a potential anti-diabetic agent and AGNEX could be useful in the treatment of diabetes mellitus.

• Preventive Nutrition and Food Science
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• 제15권3호
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• pp.176-183
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• 2010

The hypoglycemic effects of red ginsgeng-chungkukjang plus seaweeds, green laver and sea tangle, in streptozotocin (STZ)-induced diabetic rats were investigated. Five groups of male Sprague-Dawley rats weighing $140\pm10$ g (10 animals/group) were fed for four weeks with the following: nondiabetic control (NC group); STZ-induced diabetic (D group); diabetic rats fed 3% red ginseng (20%, w/w)-chungkukjang (D-RC group); diabetic rats fed RC containing 10% (w/w) green laver powder (D-RCG group); diabetic rats fed RC containing 10% (w/w) sea tangle powder (D-RCS group). Partially normalized body weight gain, FER, and blood glucose levels were observed in the D-RC, D-RCG and D-RCS groups as compared to the D group. In these three groups, serum levels of triglycerides, total cholesterol, and LDL-cholesterol were found to be lower than in the D group, whereas HDL-cholesterol levels increased. Serum insulin level in D was significantly lower than that of NC, although D-RC, D-RCG, and D-RCS almost recovered to the NC. Serum ALT activity was markedly increased in the D group, while the serum ALT levels in the D-RC, D-RCG, and D-RCS were almost the same as the NC group. Due to diabetes, hepatic xanthine oxidase (XO) activity was significantly increased and administration of red ginseng-chungkukjang or seaweeds resulted in decreased levels of the XO activity. Activity of hepatic antioxidant enzymes (superoxide dismutase and glutathione peroxidase) were significantly decreased in the D group, but the activity in the D-RC, D-RCG, and D-RCS groups were similar to that of the NC group. Results of the present study indicate that supplementation of red ginseng-chungkukjang with seaweed after the onset of diabetes ameliorated hyperglycemia via an increase in serum insulin.

• The Korean Journal of Physiology and Pharmacology
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• 제24권5호
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• pp.395-402
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• 2020

This study has investigated the effect of a potent bioflavonoid, troxerutin, on diabetes-induced changes in pro-inflammatory mediators and expression of microRNA-146a and nuclear factor-kappa-B (NF-κB) signaling pathway in aortic tissue of type-I diabetic rats. Male Wistar rats were randomly divided into four groups (n = 6/each): healthy, healthy-troxerutin, diabetic, and diabetic-troxerutin. Diabetes was induced by streptozotocin injection (60 mg/kg; intraperitoneally) and lasted 10 weeks. Troxerutin (150 mg/kg/day) was administered orally for last month of experiment. Inflammatory cytokines IL-1β, IL-6, and TNF-α, as well as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM), cyclooxygenase-II (COX-II), and inducible-nitric oxide synthase (iNOS) were measured on aortic samples by enzyme-linked immunosorbent assay. Gene expressions for transcription factor NF-κB, interleukin-1 receptor-associated kinase-1 (IRAK-1), TNF receptor-associated factor-6 (TRAF-6), and microRNA-146a were determined using real-time polymerase chain reaction. Ten-week diabetes significantly increased mRNA levels of IRAK-1, TRAF-6, NF-κB, and protein levels of cytokines IL-1β, IL-6, TNF-α, adhesion molecules ICAM-1, VCAM, and iNOS, COX-II, and decreased expression of microRNA-146a as compared with healthy rats (p < 0.05 to p < 0.01). However, one month treatment of diabetic rats with troxerutin restored glucose and insulin levels, significantly decreased expression of inflammatory genes and pro-inflammatory mediators and increased microRNA level in comparison to diabetic group (p < 0.05 to p < 0.01). In healthy rats, troxerutin had significant reducing effect only on NF-κB, TNF-α and COX-II levels (p < 0.05). Beside slight improvement of hyperglycemia, troxerutin prevented the activation of NF-κB-dependent inflammatory signaling in the aorta of diabetic rats, and this response may be regulated by microRNA-146a.