• Title/Summary/Keyword: streptozotocin

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Inhibitory Effects of Hydroxybrazilin on the Platelet Phospholipase $A_2$ Activities in Normal and Streptozotocin Induced Diabetic Rats (Streptozotocin 유도 당뇨병 랫드의 혈소판 Phospholipase $A_2$ 활성에 미치는 Hydroxybrazilin의 영향)

  • Moon, Chang-Hyun;Lim, Dong-Soon;Cho, Tae-Soon;Kim, Ji-Young
    • YAKHAK HOEJI
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    • v.38 no.1
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    • pp.97-101
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    • 1994
  • Platelets play a very important role in nomal hemostasis and their functions are more enhanced in various pathogenic states than in normal state. Especially it has been postulated that abnormal platelet and endothelium function might be major factors of microcirculatory disturbance in diabetes mellitus. Hydroxybrazilin, a phenolic constituent of Hematoxylon campechianum has been examined for its inhibitory effect on platelet aggregation. Its antiaggregatory effect might be mediated through the decrease of ATP release from dense granule and those of thromboxane $A_2$ production in normal and streptozotocin induced diabetic rats. The present study was undertaken to gain insight into the mechanism that hydroxybrazilin inhibited thromboxane $A_2$ production in platelets. Thus we measured the effect of hydroxybrazilin on phospholipase $A_2$, a rate limiting step of thromboxane $A_2$ production, in normal and streptozotocin induced diabetic rats. Hydroxybrazilin significantly inhibited the platelet phospholipase $A_2$ activity in normal and streptozotocin induced diabetic rats.

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Study on the Hypoglycemic Action of the Fat Soluble Fraction of Panax ginseng C.A. Meyer in Streptozotocin Induced Diabetic Rats (인삼 지용성분획의 고혈당 강하작용에 관한 연구)

  • Joo, Chung-No;Koo, Ja-Hyun;Lee, Hee-Bong
    • Journal of Ginseng Research
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    • v.17 no.1
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    • pp.13-21
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    • 1993
  • We attempted in this study to understand the hypoglycemic action of the fat soluble fraction of red ginseng roots in streptozotocin injected diabetic rats, through its actions on several enzymes relating to carbohydrate metabolism of the 1eve1 to compare with those of ginsenosides in streptozotocin injected diabetic rats. It was realized that the increased level of glucose, ketone bodies, lactate, nonesterified fatty acids and triacylglycerol in blood was significantly decreased and the decreased liver glycogen content of streptozotocin injected rats were appreciably moderated by intraperitoneal injection of the fat soluble fraction of red ginseng roots as shown in the saponin injected diabetic rats. The deceased activities of liver enzymes relating to carbohydrate metabolism such as phosphofructokinase, glucokinase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and acetyl CoA carboxylase of streptozotocin induced diabetic rats were also sufficiently modified by the intraperitoneal injection of the above fat soluble fraction as shown in the ginsenoside injected streptozotocin induced rats.

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Hypoglycemic Effect of Fractions of Cassia tora Extract in Streptozotocin-Induced Diabetic Rats (결명자 분획물이 당뇨 유발 흰쥐의 혈당에 미치는 영향)

  • 임숙자;한혜경
    • Korean journal of food and cookery science
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    • v.13 no.1
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    • pp.23-29
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    • 1997
  • The hypoglycemic effect of fractions of methanol extract of Cassia tora was investigated in diabetic rats. Sprague-Dawley male rats weighing 180∼230 g were divided into 6 groups. Diabetes was induced in the male rats by intravenous injection of streptozotocin at a dose of 45 mg/kg dissolved in citrate buffer (pH 4.5). The diabetic animals then had plasma glucose concentration of above 300 mg/㎗. Fractions of methanol extract of Cassia tora were administered orally into the diabetic rats for 14 days after streptozotocin injection. The food intake and body weight gain were monitored and plasma levels of glucose, triglyceride, free fatty acid, HDL-cholesterol, cholesterol and ALT activity were determined. Levels of glycogen, cholesterol and triglyceride in liver were analysed. Weights of liver and kidney were lighter in all the fraction-administered groups than streptozotocin-control group. Plasma glucose level was significantly decreased by the administration of butanol fraction at 14 days. Plasma triglyceride levels were lower in chloroform, butanol and H$_2$O fraction-administered groups compared to streptozotocin-control group. Plasma cholesterol and HDL-cholesterol levels were not significantly different in all groups. Administrations of each of the four fractions have decreased plasma free fatty acid level, ALT activity and liver triglyceride levels in the diabetic rats. Liver glycogen levels in chloroform, butanol and H$_2$O fraction-administered groups were higher than streptozotocin-control group. It is suggested from the results that butanol fraction of methanol extract of Cassia tora may contain the antihyperglycemic compounds.

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Fine Structure of Suxtaglomerular Cells in Streptozotocin-treated Normal and Genetically Diabetic KK Mice (Streptozotocin이 정상 ICR 생쥐 및 유전성 당뇨병을 가진 KK생쥐 사구체곁세포의 미세구조에 미치는 영향)

  • 최월봉;최창도원무호김남주
    • The Korean Journal of Zoology
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    • v.35 no.3
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    • pp.372-382
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    • 1992
  • 당뇨병유발제인 streptozotocin이 생쥐 신장 사구체곁세포의 미세구조에 어떠한 영향을 미치는 지를 알아보고자 일반계통인 ICR생쥐와 유전성 당뇨병계통인 KK생쥐에 streptozotocin을 투여하여 경시적으로 각 동물의 신장 사구체곁세포의 미세구조의 변화를 관찰하였다. Streptozotocin을 투여한 ICR생쥐의 사구체곁세포는 3일째부터 과립형질내세망의 미약한 팽창과 과립내에 대소 공포의 출현 및 용해소체가 간혹 관찰되었다. 그후 시간이 지남에 따라 더욱 심하여 특히 2주 및 4주에서는 과립형질내세망의 팽창, 사립체, 골지장치 및 리보소곤 등이 소수 출현하였는데 비해 대소 용해소체는 많이 관찰되었으며 심한 탈과립으로 인해 세포질내 과립의 면적이 현저히 감소되었다. 그러나 KK생쥐의 실험군에서는 전 실험군에 걸쳐 퇴행성변화가 적었으며 ICR 생쥐 실험군에 비해 그 영향이 훨씬 적었다. 이상의 결과를 종합하여 보면 정상 ICR생쥐에 streptozotocin을 투여하자 되면 ICR생쥐 사구체곁세포에서 과립의 유의한 감소 및 세포내 미세구조의 퇴행성변화가 뚜렷한데 비해 KK생쥐 실험군에서는 ICR생쥐 실험군에 비해 손상을 적게 받았는데 이는 KK생쥐가 갖고 있는 당뇨병에 대한 내성에 의해 영향을 적게 미치는 것이 아닌가 추측된다.

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Effects of Indongdeung Jigolpi-tang applied to Soyangin on Hyperglycemic Rats induced by Streptozotocin (소양인(少陽人)에 응용(應用)되는 인동등지골피탕(認冬藤地骨皮湯)이 Streptozotocin 투여(投與) 고혈당(高血糖) 백서(白鼠)에 미치는 영향(影響))

  • Ko, Ki Duk;Hong, Sun-Yong
    • Journal of Sasang Constitutional Medicine
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    • v.2 no.1
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    • pp.149-166
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    • 1990
  • In order to investigate experimented effects of Indongdeung Jigolpi-Tang, which is applied to Soyangin, to diabetes, the measurement, comparison and observation made on the contents of volumes of blood glucose, total cholesterol, triglyceride, phospholipid, total protein and electrolyte($K^+$, $Na^+$) in blood serum by giving a high blood glucose, induced by streptozotocin, to hyperglycemic rats, dosing the cooked liquid of I.J.T., and following conclusion was attained. 1. The volume of glucose urine, induced by streptozotocin to hyperglycemic rats, was shown an increase in comparision to a normal flock when $12.50m{\ell}/kg$ of I.J.T. dosed to the rats and checked after two and four weeks and thereby, a sinificant reduction in the volume of blood glucose was made. 2. The volume of total cholesterol of blood serum in the diabetic rats, induced by streptozotocin, was increased in comparision to the normal flock, and in the fouth week of dosing $1.25m{\ell}/kg$ of I.J.T., a significant reduction of total cholesterol volum was shown in the blood serum. 3. The volume of triglyceride in the blood serum of the diabetic rats, induced by the streptozotocin, was increased in comparision to the normal flock, and with dosing $1.25m{\ell}/kg$ and $12.50m{\ell}/kg$ of I.J.T., a significant reduction of triglyceride volium was shwon in the blood serum after second and fourth week. 4. The volume of phospholipid in the blood serum of the diabetic rats, induced by the streptozotocin, was somewhat reduced in comparision to the normal flock, and with dosing $1.25m{\ell}/kg$ of I.J.T., a significant reduction of phospholipid volium in the blood serum was shown after first and second week. 5. The volume of total protein in the blood serum of the diabetic rats, induced by the streptozotocin, was somewhat reduced in comparison to the normal flock however, with dosing the I.J.T., no significant change on the volium of total protein was made in the blood serum. 6. The volume of potassium in the blood serum of the diabetic rats, induced by the streptozotocin, was increased in comparision to the normal flock however, with dosing the I.J.T., no significant change of potassium content was made in the blood serum. 7. The volume of sodium in the blood serum of the diabetic rats, induced by the streptozotocin, was somewhat reduced in comparision to the normal flock, and with dosing $12.50m{\ell}/kg$ of the I.J.T., a significant increase was shown in the blood serum after first week. Soyangin, accompanying with a middle and upper heat, the I.J.T. - that has a merits of cleaning up fever, solving fever, solving poison, solving thirst and restoring exhaustion - can be proved that it has a blood sugar reduction effect and it is considered that it can be meritorious for strengthening vitality, further, many other exhausting diseases, and can actively used for the cases such as thirst causing disease and a disease that causes an abnormal food hunger, thirst causing and frequent going to pass urine, in particular.

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Effects of Diabetes Mellitus on the Disposition of Tofacitinib, a Janus Kinase Inhibitor, in Rats

  • Gwak, Eun Hye;Yoo, Hee Young;Kim, So Hee
    • Biomolecules & Therapeutics
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    • v.28 no.4
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    • pp.361-369
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    • 2020
  • Tofacitinib, a Janus kinase inhibitor, was developed for the treatment of rheumatoid arthritis. Recently, it has been associated with an increased change in arthritis development in patients with diabetes. Herein, we evaluated the pharmacokinetics of tofacitinib after intravenous (10 mg/kg) and oral (20 mg/kg) administration to rats with streptozotocin-induced diabetes mellitus and control rats. Following intravenous administration of tofacitinib to rats with streptozotocin-induced diabetes mellitus, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was significantly smaller (33.6%) than that of control rats. This might be due to the faster hepatic intrinsic clearance (112%) caused by an increase in the hepatic cytochrome P450 (CYP) 3A1(23) and the faster hepatic blood flow rate in rats with streptozotocin-induced diabetes mellitus than in control rats. Following oral administration, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was also significantly smaller (55.5%) in rats with streptozotocin-induced diabetes mellitus than that in control rats. This might be due to decreased absorption caused by the higher expression of P-glycoprotein and the faster intestinal metabolism caused by the higher expression of intestinal CYP3A1(23), which resulted in the decreased bioavailability of tofacitinib (33.0%) in rats with streptozotocin-induced diabetes mellitus. In summary, our findings indicate that diabetes mellitus affects the absorption and metabolism of tofacitinib, causing faster metabolism and decreased intestinal absorption in rats with streptozotocin-induced diabetes mellitus.

Effects of Gentiana scabra Bunge var.buergeri Max. Extract on Blood Glucose and Lipid Composition in Streptozotcin induced Hyperglycemic Rats (용담(Gentiana scabra Bunge var.buergeri Max.) 추출액이 Streptozotocin 유발 당뇨성 흰주의 혈당 및 지질 성분에 미치는 영향)

  • 김용균;김한수
    • Journal of Life Science
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    • v.8 no.4
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    • pp.381-386
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    • 1998
  • This study was designed to observe the effects of the feeding Gentiana scabra Bunge var.buergeri Max. extract on the improvement of the blood glucose, lipids in the serum of streptozotcin(55mg/kg of body weight, I.P. injection) induced hyperglycemic rats (S.D. strain, ) fed the experimental diets for 4 weeks. Concentrations of blood glucose were significantly higher in the streptozotocin administration(I.P.) groups (group 2(streptozotcin+water), 3(streptozocin+Gentiana scabra Bunge extract), 4(streptozotocin+cholesterol+water), 5(streptozotocin+cholesterol+Gentiana scabra Bunge extract) than those in the control group(group 1(water)). Bolld glucose concentrations were rather lower in the group 3(streptozotocin+Gentiana scabra Bunge extract)than in the group 2(streptozotocin+water), and then those of the group 5 were rather lower than in the group 4. There was almost little significance among the groups. concentrations of total cholesterol in serum were lower in the group 5 than those in the group 4, and the group 3 were rather lower than in the group 2. Concentrations of LDL-cholesterol in serum were significantly lower in the group 3 than those 2. In the ratio of HDL-cholesterol concentrations to total cholesterol concentrations, Gentiana scabra Bunge extract administration groups were higher percentage than the other goups. Concentrations of free cholesterol and cholesteryl ester in serum were rather lower in the groups 3,5 than the other groups, and then those of the group were higher percentage than the other groups. concentrations of free cholesterol and cholesteryl ester in serum were rather lower in the groups 3,5 than the groups, and then those of the group 3 were significantly lower than in the group 4. Concentrations of triglyceride and phospholipid in serum were decreased in the group 3 than in the other groups. The activities of aspartate aminotransferase and alanine aminotransferase in serum were increased in the all experimental groups than in the control group. From the above research, the Gentiana scabra Bunge var.buergeri Max. extracts were effective on the improvement of the lipid compositions in serum of streptozotcin induced hyperglycemic and hypercholosterolemic rats.

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Antidiabetic Activity of an Ayurvedic Formulation Chaturmukha Rasa: A Mechanism Based Study

  • Sharma, Akansha;Tiwari, Raj K;Sharma, Vikas;Pandey, Ravindra K;Shukla, Shiv Shnakar
    • Journal of Pharmacopuncture
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    • v.22 no.2
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    • pp.115-121
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    • 2019
  • Objectives: The objective of this study was to evaluate antidiabetic activity of Chaturmukha rasa based on streptozotocin induced diabetes model, alpha amylase inhibitory activity, alpha Glucosidase inhibitory activity and inhibition of sucrase. Methods: Chaturmukha rasa was prepared as per Ayurvedic formulary. Antidiabetic activity was measured in experimentally streptozotocin induced rats. The dose was taken as 45 mg/kg, i.p. The antidiabetic activity of Chaturmukha rasa was compared Triphala Kwatha, a marketed formulation. Further In vitro $\acute{\alpha}$- Amylase Inhibitory Assay, In vitro salivary amylase Inhibitory Assay, In vitro ${\alpha}-Glucosidase$ Inhibitory Assay and In vitro Sucrase Inhibitory Assay was performed with respect to Chaturmukha rasa. The IC50 value was calculated for all the above activity. Results: Streptozotocin with Acarbose showed significant decrease in blood glucose level whereas streptozotocin with Triphala kwatha showed more decrease in blood glucose level than Streptozotocin with Acarbose. The combination of Streptozotocin + Triphala kwatha + Chaturmukha rasa showed a significant decrease in blood glucose level on 21st day. In vitro $\acute{\alpha}$- Amylase Inhibitory Assay the Chaturmukha rasa showed IC50 value $495.94{\mu}l$ when compared with Acarbose $427.33{\mu}l$, respectively. In the ${\alpha}-Glucosidase$ Inhibitory Assay Chaturmukha rasa showed IC50 value $70.93{\mu}l$ when compared with Acarbose $102.28{\mu}l$, respectively. In vitro Sucrase Inhibitory Assay Chaturmukha rasa showed IC50 value $415.4{\mu}l$ when compared with Acarbose $371.43{\mu}l$, respectively. Conclusion: This study supports that Chaturmukha rasa may inhibit diabetes by inhibition of salivary amylase or alpha Glucosidase or sucrase. This may be the mechanism by which Chaturmukha rasa inhibits diabetes. Further this study supports the usage of Chaturmukha rasa for the management of diabetes.

Effects of Iksujisundan on Renal Function, Peroxynitrite Scavenging Activity and Polyol Pathway in Streptozotocin-induced Diabetic Rats (익수지선단(益壽地仙丹)이 Streptozotocin으로 유발된 당뇨병 흰쥐의 신기능, 활성산소, 활성질소 및 Polyol Pathway에 미치는 영향)

  • Jeon, Chang-Min;Jeong, Ji-Cheon
    • The Journal of Korean Medicine
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    • v.28 no.1 s.69
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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.

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Effects of Gamigukihwandong-hwan on Renal Function, Oxidative Stress and Polyol Pathway in Diabetic Nephropathy Rats (Streptozotocin으로 유발된 흰쥐의 당뇨병성 신증에서 가미구기환동환(加味枸杞還童丸)이 Oxidative Stress 및 Polyol Pathway에 미치는 영향)

  • Jeong, Hyung-Cheol;Jeong, Ji-Cheon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.3
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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.