• Title/Summary/Keyword: nitric oxide generation

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Schisandrae Fructus ethanol extract attenuates particulate matter 2.5-induced inflammatory and oxidative responses by blocking the activation of the ROS-dependent NF-κB signaling pathway

  • Lee, Hyesook;Park, Cheol;Kwon, Da Hye;Hwangbo, Hyun;Kim, So Young;Kim, Min Yeong;Ji, Seon Yeong;Kim, Da Hye;Jeong, Jin-Woo;Kim, Gi-Young;Hwang, Hye-Jin;Choi, Yung Hyun
    • Nutrition Research and Practice
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    • v.15 no.6
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    • pp.686-702
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    • 2021
  • BACKGROUND/OBJECTIVES: Schisandrae Fructus, the fruit of Schisandra chinensis Baill., has traditionally been used as a medicinal herb for the treatment of various diseases, and has proven its various pharmacological effects, including anti-inflammatory and antioxidant activities. In this study, we investigated the inhibitory effect of Schisandrae Fructus ethanol extract (SF) on inflammatory and oxidative stress in particulate matter 2.5 (PM2.5)-treated RAW 264.7 macrophages. MATERIALS/METHODS: To investigate the anti-inflammatory and antioxidant effects of SF in PM2.5-stimulated RAW 264.7 cells, the levels of pro-inflammatory mediator such as nitric oxide (NO) and prostaglandin E2 (PGE2), cytokines including interleukin (IL)-6 and IL-1β, and reactive oxygen species (ROS) were measured. To elucidate the mechanism underlying the effect of SF, the expression of genes involved in the generation of inflammatory factors was also investigated. We further evaluated the anti-inflammatory and antioxidant efficacy of SF against PM2.5 in the zebrafish model. RESULTS: The results indicated that SF treatment significantly inhibited the PM2.5-induced release of NO and PGE2, which was associated with decreased inducible NO synthase and cyclooxygenase-2 expression. SF also attenuated the PM2.5-induced expression of IL-6 and IL-1β, reducing their extracellular secretion. Moreover, SF suppressed the PM2.5-mediated translocation of nuclear factor-kappa B (NF-κB) from the cytosol into nuclei and the degradation of inhibitor IκB-α, indicating that SF exhibited anti-inflammatory effects by inhibiting the NF-κB signaling pathway. In addition, SF abolished PM2.5-induced generation of ROS, similar to the pretreatment of a ROS scavenger, but not by an inhibitor of NF-κB activity. Furthermore, SF showed strong protective effects against NO and ROS production in PM2.5-treated zebrafish larvae. CONCLUSIONS: Our findings suggest that SF exerts anti-inflammatory and antioxidant effects against PM2.5 through ROS-dependent down-regulating the NF-κB signaling pathway, and that SF can be a potential functional substance to prevent PM2.5-mediated inflammatory and oxidative damage.

Perilla frutescens Sprout Extracts Protected Against Cytokine-induced Cell Damage of Pancreatic RINm5F Cells via NF-κB Pathway (들깨 새싹 추출물의 췌장 RINm5F 세포에서 NF-κB 경로를 통한 사이토카인에 의한 손상 예방 효과)

  • Kim, Da Hye;Kim, Sang Jun;Jeong, Seung-Il;Yu, Kang-Yeol;Cheon, Chun Jin;Kim, Jang-Ho;Kim, Seon-Young
    • Journal of Life Science
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    • v.27 no.5
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    • pp.509-516
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    • 2017
  • Perilla frutescens (L.) Britton var. sprouts (PFS) is a plant of the labiatae family. The purpose of this work was to assess the preventive effects of PFS ethanolic extracts (PFSEs) on cytokine-induced ${\beta}$-cell damage. Cytokines, which are released by the infiltration of inflammatory cells around the pancreatic islets, are involved in the pathogenesis of type 1 diabetes mellitus. The combination of interleukin-$1{\beta}$ (IL-1), interferon-${\gamma}$ (IFN-${\gamma}$), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) induced formation of reactive oxygen species (ROS). Accumulation of intracellular ROS led to ${\beta}$-cell dysfunction and apoptosis. PFSEs possess antioxidant activity and thus lead to downregulation of ROS generation. Cytokines decrease cell viability, stimulate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and induce the production of nitric oxide (NO). PFSEs prevented cytokine-induced cell viability in a dose-dependent manner. Incubation with PFSE resulted in significant reduction in cytokine-induced NO production that correlated with reduced levels of the iNOS and COX-2 protein expression. Furthermore, PFSE significantly decreased the activation of nuclear factor ${\kappa}B$ (NF-${\kappa}B$) by inhibition of $I{\kappa}B{\alpha}$ phosphorylation in RINm5F cells. In summary, our results suggest that the protective effects of PFSE might serve to counteract cytokine-induced ${\beta}$-cell destruction. Findings indicate that consumption of Perilla frutescens (L.) Britton var. sprouts alleviates hyperglycemia-mediated oxidative stress and pro-inflammatory cytokine-induced ${\beta}$-cell damage and thus has beneficial anti-diabetic effects.

Antioxidant and Inhibitory Effects of Korean Panax ginseng Extract on Pro-inflammatory Mediators in LPS-stimulated RAW264.7 Macrophages (산양삼(Korean Panax ginseng) 추출물의 항산화 효과 및 LPS로 염증이 활성화된 RAW 264.7 대식세포에서의 염증매개물질 억제효과)

  • Kim, Ye-Jin;Son, Dae-Yeul
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.10
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    • pp.1371-1377
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    • 2012
  • Biological activities of Korean Panax ginseng 55% ethanol extract (KPGE) were investigated. The measured total polyphenol content of KPGE was 357.45 mg/100 g. KPGE showed the highest ${\alpha},{\alpha}$-diphenyl-${\beta}$-picrylhydrazyl (DPPH) and 2,2'-azino-bis-3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS) radical scavenging activities of 80% and 86% at 1,000 ${\mu}g/mL$, respectively. DPPH and ABTS radical scavenging activities significantly increased in a KPGE concentration-dependent manner. SOD-like activity of KPGE (1, 10, and 100 ${\mu}g/mL$) increased from 22% up to 33% at KPGE concentrations of 500 and 1,000 ${\mu}g/mL$. KPGE treatment significantly suppressed the generation of pro-inflammatory mediators, including nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and cytokines (tumor necrosis factor-alpha: TNF-${\alpha}$, interleukin-6: IL-6, interleukin-$1{\beta}$: IL-$1{\beta}$), in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. KPGE demonstrated strong anti-inflammatory activity that reduced NO and $PGE_2$ production in LPS-stimulated RAW 264.7 cells. Even low concentrations of KPGE (1 and 10 ${\mu}g/mL$) reduced $PGE_2$ and NO production in RAW 264.7 macrophages without LPS-stimulation, respectively. At concentrations of 100, 500, and 1,000 ${\mu}g/mL$, TNF-${\alpha}$, IL-$1{\beta}$ and IL-6 production were significantly suppressed. The results of our study suggest the potential of Korean Panax ginseng as an excellent antioxidant substance for inhibiting inflammatory mediators. Therefore, Korean Panax ginseng (KPGE) may be used as a therapeutic approach to various inflammatory diseases.

The Role of ROS-NF-κB Signaling Pathway in Enhancement of Inflammatory Response by Particulate Matter 2.5 in Lipopolysaccharide-stimulated RAW 264.7 Macrophages (RAW 264.7 대식세포에서 지질 다당류에 의한 미세먼지(PM2.5) 유발 염증 반응 증진에 미치는 ROS-NF-κB 신호 전달 경로의 역할)

  • Kwon, Da Hye;Kim, Da Hye;Kim, Min Yeong;Hwangbo, Hyun;Ji, Seon Yeong;Park, Seh-Kwang;Jeong, Ji-Won;Kim, Mi-Young;Lee, Hyesook;Cheong, JaeHun;Nam, Soo-Wan;Hwang, Hye-Jin;Choi, Yung Hyun
    • Journal of Life Science
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    • v.31 no.12
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    • pp.1110-1119
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    • 2021
  • The purpose of this study was to investigate whether the inflammatory response in lipopolysaccharide (LPS)-treated RAW 264.7 macrophages could be promoted by particulate matter 2.5 (PM2.5) stimulation. To this end, the levels of inflammatory parameters, reactive oxygen species (ROS) and inflammation-regulating genes were investigated in RAW 264.7 cells treated with PM2.5 in the presence or absence of LPS. Our results showed that the production levels of pro-inflammatory mediators (nitric oxide and prostaglandin E2) and cytokines (interleukin-6 and -1β) were significantly increased by PM2.5 stimulation in LPS-treated RAW 264.7 cells, which was correlated with increased expression genes involved in their production. In addition, when LPS-treated RAW 264.7 cells were exposed to PM2.5, nuclear factor-kappaB (NF-κB) expression was further increased in the nucleus, and the expression of inhibitor of NF-κB as well as NF-κB in the cytoplasm was decreased. These results suggest that the co-treatment of PM2.5 and LPS further increases the activation of the NF-κB signaling pathway compared to each treatment alone, thereby contributing to the promotion of transcriptional activity of inflammatory genes. Furthermore, although the generation of ROS was greatly increased by PM2.5 in LPS-treated RAW 264.7 cells, the NF-κB inhibitor did not reduce the generation of ROS. In addition, when the generation of ROS was artificially suppressed, the production of inflammatory mediators and the activation of NF-κB were both abolished. Therefore, our results suggest that the increase in the NF-κB-mediated inflammatory response induced by PM2.5 in LPS-treated RAW 264.7 macrophages was a ROS generation-dependent phenomenon.

Cosmeceutical activities and Anti-inflammatory effects of Shell from Persicae semen (도인(桃仁) 껍질의 화장품약리활성 및 항염 효과)

  • Joe, Woo-A;Jang, Min-Jung;Cheon, Soon-Ju;Sung, Ji-Yeun;Choi, Eun-Young;Kang, Bo-Yeon;Jung, Su-Hyun;Jeung, Yeun-Suck;Kim, Young-Sun;An, Bong-Jeun;Lee, Chang-Eon;Lee, Jin-Tae
    • The Korea Journal of Herbology
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    • v.21 no.2
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    • pp.87-93
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    • 2006
  • Objectives : In this paper, we tested the applicability of shell from Persicae semen in cosmetics through cosmeceutical activities including anti-oxidant, tyrosinase inhibition and anti-inflammatory effects. Methods : Persicae semen, which had been extracted, concentrated, and freeze drying with water and ethanol, have been used for the experiment. The effects on electronic donating ability, SOD-like activity, xanthine oxidase inhibition, whitening effect have been investigated in the cosmeceutical activity measurement of function experiment. Results : In the electron donating ability test, 1,000ppm of EPS (ethanol extract of shell from Persicae semen) showed an effect of 87%. SOD-like activities showed 93% at the 10,000ppm of WPS (water extract of shell from Persicae semen). In the xanthine oxidase inhibition test, 1,000ppm of BHA showed an effect of 27%, while EPS showed an effect of 62%. We were able to get an effect of 95% from EPS at 10,000 ppm in the tyrosinase inhibition test. In the anti-inflammatory test, the EPS inhibited the generation of nitric oxide. In the case of the EPS, there were no signs of cytotoxicity against raw 264.7 and anti-inflammatory effects could be identified when the manifestation of iNOS was decreased. Conclusion : Therefore, the EPS has potential as an effective raw materials for cosmetic.

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Vaccinium bracteatum Thunb. Exerts Anti-Inflammatory Activity by Inhibiting NF-κB Activation in BV-2 Microglial Cells

  • Kwon, Seung-Hwan;Ma, Shi-Xun;Ko, Yong-Hyun;Seo, Jee-Yeon;Lee, Bo-Ram;Lee, Taek Hwan;Kim, Sun Yeou;Lee, Seok-Yong;Jang, Choon-Gon
    • Biomolecules & Therapeutics
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    • v.24 no.5
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    • pp.543-551
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    • 2016
  • This study was designed to evaluate the pharmacological effects of Vaccinium bracteatum Thunb. methanol extract (VBME) on microglial activation and to identify the underlying mechanisms of action of these effects. The anti-inflammatory properties of VBME were studied using lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. We measured the production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase (COX)-2, prostaglandin $E_2$ ($PGE_2$), tumor necrosis factor-alpha (TNF-${\alpha}$), interleukin-1 beta (IL-$1{\beta}$), and interleukin-6 (IL-6) as inflammatory parameters. We also examined the effect of VBME on intracellular reactive oxygen species (ROS) production and the activity of nuclear factor-kappa B p65 (NF-${\kappa}B$ p65). VBME significantly inhibited LPS-induced production of NO and $PGE_2$ and LPS-mediated upregulation of iNOS and COX-2 expression in a dose-dependent manner; importantly, VBME was not cytotoxic. VBME also significantly reduced the generation of the pro-inflammatory cytokines TNF-${\alpha}$, IL-$1{\beta}$, and IL-6. In addition, VBME significantly dampened intracellular ROS production and suppressed NF-${\kappa}B$ p65 translocation by blocking $I{\kappa}B-{\alpha}$ phosphorylation and degradation in LPS-stimulated BV2 cells. Our findings indicate that VBME inhibits the production of inflammatory mediators in BV-2 microglial cells by suppressing NF-${\kappa}B$ signaling. Thus, VBME may be useful in the treatment of neurodegenerative diseases due to its ability to inhibit inflammatory mediator production in activated BV-2 microglial cells.

Wound Healing Effects of Lespedeza cuneata Extract (야관문 추출물의 창상치유 효과)

  • Jung, Hee Kyoung;Kim, Kil-Soo;Jeong, Yoo Seok
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.3
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    • pp.374-380
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    • 2014
  • In this study, the anti-inflammatory effects of Lespedeza cuneata extract on macrophages and wound-healing in wound-induced animal experiments were investigated. In an anti-inflammatory test, 0.1 mg/mL of Lespedeza cuneata extract did not affect growth of RAW 264.7 cells, and Lespedeza cuneata extract suppressed nitric oxide (NO) generation from inflammation-induced macrophages in a concentration-dependent manner. Wounds on the skin of rats were treated with vehicle containing Lespedeza cuneata extract (SSP), vehicle (SCO), and commercial ointment (CCO). The wound and scar sizes in the SSP group were significantly reduced in comparison to the SCO and CCO groups (P<0.05). The epidermis and dermis of the SSP group also recovered faster than the SCO group based on Masson's trichrome staining. The gene expression levels of vascular endothelial growth factor (VEGF) decreased and transforming growth factor-beta 1 (TGF-${\beta}1$) increased in wound tissue from the SSP group compared to that from the SCO group. These results show that Lespedeza cuneata extract accelerates wound-healing through anti-inflammatory activity and induction of collagen regeneration as well as reduces the scar area surrounding wounds. Accordingly, Lespedeza cuneata extract could be useful as a cosmeceutical in the cosmetic industry.

The Effects of LR3 and SP6 Acupuncture on Liver Damage of Streptozotocin-induced Diabetic Mice (태충혈과 삼음교혈의 침 자극이 Streptozotocin으로 유발된 당뇨쥐의 간 손상에 미치는 영향)

  • Kim, Sung Jin;Lee, Yun Kyu;Lee, Hyun Jong;Kim, Jae Soo
    • Journal of Acupuncture Research
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    • v.33 no.3
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    • pp.29-43
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    • 2016
  • Objectives : The purpose of this study was to investigate the effect of LR3 and SP6 acupuncture on liver damage of streptozotocin-induced diabetic mice. Methods : Male ICR mice were divided into four groups, consisting of the normal mice group(N), acupuncture-free diabetic mice group(Con), LR3-acupuncture diabetic mice group(LR3) and SP6-acupuncture diabetic mice group(SP6). The following measurements were taken: Body weight, food intake and water intake for 2 weeks; liver weight, and glucose levels in the serum and liver; ALT and AST in the serum; reactive oxygen species(ROS), reduced glutathione(GSH) and oxidized glutathione(GSSG) in the liver; and lastly, receptor for advanced glycation endproducts( RAGE), $N{\varepsilon}-carboxymethyl$ lysine(CML), $N{\varepsilon}-carboxyethyl$ lysine(CEL), phosphorylation of inhibitory kappa B alpha($p-I{\kappa}B{\alpha}$), nuclear factor-kappa B($NF-{\kappa}B$), activator protein-1(AP-1), cyclooxygenase-2(COX-2), inducible nitric oxide synthase(iNOS), tumor necrosis factor-alpha($TNF-{\alpha}$), ${\beta}-actin$, cytochrome c and caspase in the liver. Results : The liver weight and GSH/GSSG ratio were significantly increased in SP6 compared to Con. The glucose levels in the liver were significantly decreased in LR3 compared to Con. The generation of ROS and GSSG were significantly decreased in SP6 compared to Con. The expressions of RAGE, CML, AP-1, $TNF-{\alpha}$, cytochrome c and caspase 3 were significantly decreased in LR3 compared to Con. The expressions of $p-I{\kappa}B{\alpha}$, $NF-{\kappa}B$, AP-1, COX-2, iNOS and caspase 3 were significantly decreased in SP6 compared to Con. Conclusion : It is predicted that LR3 acupuncture is related to reduced glucose levels in the liver and expressions of AGE, and that, SP6 acupuncture is related to reduced oxidative stress-related transcription factors and inflammation-related proteins. Therefore, we suggest that LR3 and SP6 acupuncture have protective effects on the liver of streptozotocin-induced diabetic mice by preventing apoptosis.

Comparison of Anti-oxidative and Anti-inflammatory Effect of Atractylodes Interspecific Hybrid Cultivar Roots (삽주 육성품종 뿌리의 항산화 및 항염증 효과 비교)

  • Jeong, Hyeon Soo;Jeong, Jin Tae;Lee, Jeong Hoon;Park, Chun Geon;Choi, Je Hun;Jang, Gwi Yeong;Kim, Jang Wook;Chang, Jae Ki;Kim, Dong Hwi;Lee, Seung Eun
    • Korean Journal of Medicinal Crop Science
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    • v.26 no.5
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    • pp.391-400
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    • 2018
  • Background: Atractylodes radix is a well-known medicinal crop having many physiological effects. This study was conducted to select useful Atractylodes japonica ${\times}$ Atractylodes macrocephala (AJM) cultivars by comparing anti-oxidative and anti-inflammatory efficacies. Methods and Results: Seven extracts from AJM cultivars were used to treat lipopolysacchride (LPS)-treated BV2 cells, and the effects on cell viability and inhibition on reactive oxygen species (ROS) and nitric oxide (NO) production were analyzed. In vitro scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and peroxynitrite ($NOO^-$) radicals were also investigated. Contents of total phenol, atractylenolide I, and atractylenolide III in the AJM extracts were measured using high performance liquid chromatography (HPLC) or spectrophotometry. The experiments show that none of the seven extracts was cytotoxic above 89.2% at $20-250{\mu}g/m{\ell}$. Extracts of Gowon, Dawon, Sangchul, and Huchul inhibited ROS generation in a dose-dependent manner, and Sangchul extract showed the highest inhibition on ROS production. All the AJM extracts showed effective inhibitory activity after on NO release in the LPS-treated BV2 cells, and Sangchul extract showed the highest activity. Sangchul extract had the most potent scavenging activities for $NOO^-$ and had some DPPH radical scavenging effect. Sangchul extract also had the highest content at total phenol and atractylenolide I content. Atractylenolide III was not detected in the AJM extracts. Conclusions: The results suggested that Sangchul was the most useful anti-oxidative and anti-inflammatory resource among the AJM cultivars.

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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