• 대한한의학회지
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• 제28권3호통권71호
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• pp.57-69
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• 2007

Objectives : Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications have shown that oxidative stress might play a major role. Therefore, many methods have been tried to regulate free oxygen radicals for treating diabetes and its complications. Ojung-hwan, composed of five crude herbs, has been considered effective for treating symptoms of aging. In male ob/ob mouse of severe obesity, hyperinsulinemia and hyperlipidemia, which are features of NIDDM, the hyperglycemic activities and mechanisms of Ojung-hwan were examined. Methods : Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed a diet of chow supplemented with 30 and 90 mg Ojung-hwan per 1 kg of body weight for 14 days. The effects of Ojung-hwan extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of superoxide anion radical (${\cdot}\;O{_2}{^-}$), MDA+HAE, GSH/GSSG ratio, and also the enzyme activities involved in polyol pathway. Results : Ojung-hwan lowered the levels of serum glucose and insulin in a dose-dependent manner. Total cholesterol, triglyceride and free fatty acid levels decreased, while the HDL-cholesterol level increased, in Ojung-hwan treated groups. Renal aldose reductase and sorbitol dehydrogenase activities increased in the ob/ob mice, whereas they were inhibited in the Ojung-hwan treated groups. Ojung-hwan inhibited the generation of ${\cdot}\;O{_2}{^-}$ in the kidney. Finally, MDA+HAE levels increased and GSH/GSSG ratio decreased in the ob/ob mice, whereas they improved in the Ojung-hwan treated groups. Conclusions : Ojung-hwan showed antidiabetic and antihyperlipidemic activities by regulating theactivities of polyol pathway enzymes, scavenging reactive oxygen species and reducing the MDA+HAE levels in the ob/ob mice.

• 동의생리병리학회지
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• 제22권2호
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• pp.350-356
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• 2008

Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Cheonghyul-san has been known to be effective for the antidiabetic, antihyperlipidemic and antiobesitic prescription, and composed of four crude herbs. In male ob/ob mouse with severe obesity, hyperinsulinemia, hypergiycemia, hyperlipidemia, the acting mechanisms of Cheonghyul-san were examined. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 7.5, 15 and 30 mg Cheonghyul-san per 1 kg of body weight for 14 days. The effects of Cheonghyul-san extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of reactive oxygen species (ROS), MDA+HAE, GSH and also the enzyme activities involved in polyol pathway. Cheonghyul-san lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Cheonghyul-san treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Cheonghyul-san-administered groups. Cheonghyul-san inhibited the generation of ROS in the kidney. Finally, MDA+HAE level was increased and the GSH level was decreased in the ob/ob mice, whereas those were improved in the Cheonghyul-san-administered groups. The results suggested that Cheonghyul-san exerted the antidiabetic and antihyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging ROS, regulating the MDA+HAE and GSH levels in the ob/ob mice.

• 동의생리병리학회지
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• 제21권5호
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• pp.1163-1169
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• 2007

Effects of Sotosaja hwan on Blood Glucose, Hyperlipidemia, Polyol Pathway and Antioxidative Mechanism in ob/ob Mouse Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Sotosaja-hwan has been known to be effective for the antiaging and composed of four crude herbs. In male ob/ob mouse in severe obesity, hyperinsulinemia and hyperlipidemia, which are features of NIDDM, the hyperglycemic activites and mechanisms of Sotosaja-hwan were examined. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57/BL6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 30 and 90 mg Sotosaja-hwan per 1 kg of body weight for 14 days. The effects of Sotosaja-hwan extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of superoxide anion radical $({\cdot}O_2)$, MDA+HAE, GSH/GSSG ratio, and also the enzyme activities involved in polyol pathway. Sotosaja-hwan lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Sotosaja-hwan treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Sotosaja-hwan-administered groups. Sotosaja-hwan inhibited the generation of ${\cdot}O_2$ in the kidney. Finally, MDA+HAE levels was increased and GSH/GSSG ratio was decreased in the ob/ob mice, whereas those were improved in the Sotosaja-hwan-administered groups. Sotosaja-hwan showed the antidiabetic and anti hyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging reactive oxygen species and reducing the MDA+HAE levels in the ob/ob mice.

• 대한한의학회지
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• 제28권1호통권69호
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• pp.237-248
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• 2007

Objectives : Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Iksujisundan has been known to be effective for the treatment of diabetes. The present study was carried out to investigate the effect of Iksujisundan on renal function, peroxynitrite(ONOO-) scavenging activity and polyol pathway in streptozotocin-induced diabetic rats. Methods : The crushed Iksujisundan was extracted 3 times, each time with 3 volumes of methyl alcohol at 60$^{\circ}C$ for 24 h. The extract was filtered and evaporated under a reduced pressure using a rotary evaporator to yield 87.8g. Iksujisundan extract was orally administreted at 100 mg per 1 kg of body weight for 20 days to the diabetic rats induced by streptozotocin(60mg/kg). The effects of Iksujisundan extract on the streptozotocin-induced diabetic rats were observed by measuring the serum level of glucose, insulin, lipid components, creatinine and BUN, and also the kidney levels of superoxide anion radical(${\cdot}$O2-), nitric oxide(NO) and ONOO-, and also the enzyme activities involved in the polyol pathway. Results : The effects of Iksujisundan on the streptozotocin-induced diabetic rats with regards to body weight, blood glucose and indulin levels, creatinine and BUN levels, total cholesterol and triglyceride lavels, and HDL-cholesterol levels were all shown to be good enough to prevent and cure the diabetes and its complications. Iksujisundan inhibited the generation of ${\cdot}$O2-,NO and ONOO- in the kidney of streptozotocin-induced diabetic rats. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the streptozotocin-induced diabetic rats were reversed toward natural activities. Conclusions : Iksujisundan might inhibit the development of diabetes and its complications by scavenging reactive oxygen and nitrogen species, thereby by reducing oxidative stresses and also by regulating the activities of polyol pathway enzymes, all of which could help to recover kidney function.

• 동의생리병리학회지
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• 제21권3호
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• pp.671-678
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• 2007

Diabetes is a disease in which the body does not produce or properly use insulin. Etiological studies of diabetes and its complications showed that oxidative stress might play a major role. Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Gamigukihwandong-hwan has been known to be effective for the treatment of diabetes. The present study was carried out to investigate the effect of Gamigukihwandong-hwan on renal function, peroxynitrite (ONOO$^-$) scavenging activity and polyol pathway in streptozotocin-induced diabetic rats. The crushed Gamigukihwandong-hwan was extracted 3 times, each time with 3 volumes of methyl alcohol at 60$^{\circ}C$ for 24 h. The extract was filtered and evaporated under a reduced pressure using a rotary evaporator to yield 74.95 g. Gamigukihwandong-hwan extract was oral-administered 100 mg per 1 kg of body weight for 20 days to the diabetic rats induced by streptozotocin (60 mg/kg). The effects of Gamigukihwandong-hwan extract on the streptozotocin-induced diabetic rats were observed by measuring the serum level of glucose, insulin, lipid components, creatinine and BUN, and also the kidney levels of superoxide anion radical (${\cdot}O_2^-$), nitric oxide (NO) and ONOO$^-$, and also the enzyme activities involved in polyol pathway. The Effects of Gamigukihwandong-hwan on the streptozotocin-induced diabetic rats with regards to body weight, blood glucose and insulin levels, creatinine and BUN levels, total cholesterol and triglyceride levels, and HDL-cholesterol levels were all shown to be good enough to cure and prevent the diabetes and its complications. Gamigukihwandong-hwan inhibited the generation of ${\cdot}O_2^-$, NO and ONOO$^-$ in the kidney of streptozotocin-induced diabetic rats. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the streptozotocin-induced diabetic rats, whereas the ones in the Gamigukihwandong-hwan administered group among the streptozotocin-induced diabetic rats were reversed toward the natural activities. Gamigukihwandong-hwan might inhibit the development of diabetic nephropathy by scavenging reactive oxygen and nitrogen species, thereby by reducing oxidative stresses and also by regulating the activities of polyol pathway enzymes, all of which could help to recover the function of kidney.

• 동의생리병리학회지
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• 제23권2호
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• pp.351-359
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• 2009

Etiological studies of diabetes and its complications showed that oxidative stress might play a major role, Therefore, many efforts have been tried to regulate free oxygen radicals for treating diabetes and its complications. Mori Fructus extract has been known to be effective for the antidiabetic, antihyperlipidemic and antiobesitic prescription, and composed of four crude herbs, The aim of this study was to investigate the effect of Mori Fructus extract in male ob/ob mouse with severe obesity, hyperinsulinemia, hyperglycemia, hyperlipidemia. Mice were grouped and treated for 5 weeks as follows. Both the lean (C57BL/6J black mice) and diabetic (ob/ob mice) control groups received standard chow. The experimental groups were fed with a diet of chow supplemented with 7.5, 15 and 30 mg Mori Fructus extract per 1 kg of body weight for 14 days. The effects of Mori Fructus extract on the ob/ob mice were observed by measuring the serum levels of glucose, insulin, lipid components, and the kidney levels of reactive oxygen species (ROS), MDA+HAE, GSH and also the enzyme activities involved in polyol pathway. Western blotting was performed using anti-AGE, anti-RAGE respectively. Mori Fructus extract lowered the levels of serum glucose and insulin in a dose dependent manner. Total cholesterol, triglyceride and free fatty acid levels were decreased, while the HDL-cholesterol level was increased, in Mori Fructus extract treated groups. Renal aldose reductase and sorbitol dehydrogenase activities were increased in the ob/ob mice, whereas those were inhibited in the Mori Fructus extract-administered groups. Mori Fructus extract inhibited the generation of ROS in the kidney. MDA+HAE level was increased and the GSH level was decreased in the ob/ob mice, whereas those were improved in the Mori Fructus extract-administered groups. Mori Fructus extract inhibited the expression of AGE, RAGE in the ob/ob mice. The results suggested that Mori Fructus exerted the antidiabetic and antihyperlipidemic activities by regulating the activities of polyol pathway enzymes, scavenging the ROS, decreasing the MDA+HAE level, increasing the GSH level and inhibiting the expression of AGE, RAGE in the ob/ob mice.

• KSBB Journal
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• 제9권2호
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• pp.140-146
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• 1994

A. pullulans로부터 polyol 생산 특성을 검토하기 위하여 탄소원, 수분활성의 영향을 검토하였다. 생산된 polyol 중에서 mannitol이 주성분이었고 소량의 glycerol이 함께 생산되었다. 검토된 탄소원 중 sucrose, glucose, fructose, mannose를 단일 탄소원으로 사용하였을 때 mannitol을 생산할 수 있었으며, 20% sucrose 배지에서 polyol 생산량이 최대였고 이때 대당 mannitol의 수율($Yp_{p/s}$)은 0.227이었다 두 종류의 유용한 탄소원인 glucose와 sucrose에 대한 초기기질농도에 대한 $Yp_{p/s}$는 거의 일정한 값을 보여, 일반적인 내삼투성 미생물과는 달리 첨가된 염(NaCl, KCI)의 농도가 증가할수록, 즉 수분활성이 낮은 조건에서는 오히려 mannitol의 생산량이 낮아졌으며, 상대적으로, glycerol의 양은 증가하였다 실험결과를 종합해 볼 때, A. pullulans에 의한 polyol 중, glycer이의 경우는 다른 내삼투성 미생물의 경우와 같이 생산되지만, mannitol의 경우는 sucrose, glucose 등의 유용한 탄소원들의 대사과정 중에 인산화경로(phosphate pathway)과 환원효소작용(enzymatic dehydrogenation)을 통해 생성되는 발효산물 이라는 결론을 얻었다.

• 대한한방내과학회지
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• 제25권2호
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• pp.288-297
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• 2004

Objective : This study was undertaken to investigate how Bombycis corpus (BC) effects the development and progress of complications occurring in Diabetes Mellitus (DM). Methods : Laboratory rats were seperated into three groups; normal, rats with DM and treated with BC, and rats with DM and not treated. In this study DM was experimentally induced through injection of streptozotocin. The BC treated group was given BC extract p.o. for 15 days. Then, The activities of glucose phosphatic enzymes and polyol pathway channels were observed. Results : The blood glucose level greatly increased in the DM groups after injection of streptoztocin, but it significantly decreased in the BC treated group. Significantly enhanced levels of serum insulin levels were seen in the BC treated group, while supressed levels were seen in the untreated DM group. Weight was recovered by the BC treated group, matching the normal group. Decreased enzyme activity of aldose reductase, sorbitol dehydrogenase and glucose-6-phosphatase were seen in BC treated diabetic rats. Increased enzyme activity, of the glucokinase and hexokinase were seen in BC treated diabetic rats. Conclusions : This study suggests that BC normalized the blood glucose and serum insulin levels destablized by DM. Because increased activity of glucose phosphatic enzymes, glucokinase and hexokinase, and decreased glucose-6-phosphatase activity, and suppression of polyol pathway enzymes, aldose reductase and sorbitol dehydrogenase, were all seen, these observations suggest that BC suppresses blood glucose levels and prevents complications due to DM.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.184-184
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• 1998

Aldose reductase(AR), a rate-limiting enzyme in the polyol pathway, has been demonstrated to cause the intracellular accumulation of sorbitol or galactitol and hence to play key roles not only in the cataract formation in the lens but also in the pathogenesis of diabetic complications such as neuropathy, retinopathy and nephropathy, etc. In a series of investigations to evaluate potential AR inhibitors from medicinal plants, we have shown that some hot water extracts exhibited a significant inhibition of a significant inhibition of bovine lens AR in vitro. Among active plants, the roots of Angelica dahuria (Umbelliferae) were shown to have relatively potent AR inhibitory activity. Systematic fractionation of the ether soluble fraction monitored by bioassay led to isolation of two furanocoumarins, byakangelicin(I) and ter-O-methyl byakangelicin( II), were identified as potential AR inhibitors, their $IC_{50}$ values being 6.2 M and 2.8 M, respectively.

• The Korean Journal of Physiology and Pharmacology
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• 제5권3호
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• pp.271-278
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• 2001

Oxidative stress and methylglyoxal (MG), a reactive dicarbonyl metabolites produced by enzymatic and non-enzymatic reaction of normal metabolism, induced aldose reductase (AR) expression in rat aortic smooth muscle cells (SMC). AR expression was induced in a time-dependent manner and reached at a maximum of 4.5-fold in 12 h of MG treatment. This effect of MG was completely abolished by cyclohemide and actinomycin D treatment suggesting AR was synthesized by de novo pathway. Pretreatment of the SMC with N-acetyl-L-cysteine significantly down-regulated the MG-induced AR mRNA. Furthermore, DL-Buthionine-(S,R)-sulfoximine, a reagent which depletes intracellular glutathione levels, increased the levels of MG-induced AR mRNA. These results indicated that MG induces AR mRNA by increasing the intracellular peroxide levels. Aminoguanidine, a scanvenger of dicarbonyl, significantly down-regulated the MG-induced AR mRNA. In addition, the inhibition of AR activities with statil, an AR inhibitor, enhanced the cytotoxic effect of MG on SMC under normal glucose, suggesting a protective role of AR against MG-induced cell damages. These results imply that the induction of AR by MG may contribute to an important cellular detoxification of reactive aldehyde compounds generated under oxidative stress in extrahepatic tissues.