• BMB Reports
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• v.38 no.2
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• pp.167-176
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• 2005

Nuclear factor-E2-related factor 2 (Nrf2) is known as a key regulator of ARE-mediated gene expression and the induction of Phase II detoxifying enzymes and antioxidant enzymes, which is also a common property of many chemopreventive agents. In the present study, we investigated the regulatory role of different chemopreventive agents including sulforaphane (SUL), allyl isothiocyanate (AITC), indole-3-carbinol (I3C), and parthenolide (PTL), in the expression and degradation of Nrf2 and the induction of the antioxidant enzyme HO-1. SUL strongly induced Nrf2 protein expression and ARE-mediated transcription activation, retarded degradation of Nrf2 through inhibiting Keap1, and thereby activating the transcriptional expression of HO-1. AITC was also a potent inducer of Nrf2 protein expression, ARE-reporter gene and HO-1 but had little effect on delaying the degradation of Nrf2 protein. Although PTL and I3C could induce ARE reporter gene expression and Nrf2 to some extent, they were not as potent as SUL and AITC. However, PTL dramatically induced the HO-1 expression, which was comparable to SUL, while I3C had no effect. In addition, when treated with SUL and PTL, inhibition of proteasome by MG132 did not cause additional accumulation of Nrf2, suggesting the involvement of other degradation mechanism(s) in the presence of these compounds such as SUL and PTL. In summary, the results of our current study indicated that different chemopreventive compounds have different regulatory properties on the accumulation and degradation of Nrf2 as well as the induction of cellular antioxidant enzyme HO-1.

• Nutrition Research and Practice
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• v.8 no.4
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• pp.398-403
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• 2014

BACKGROUND/OBJECTIVES: Ultraviolet B (UVB) irradiation on skin can induce production of reactive oxygen species (ROS), which cause expression of matrix metalloproteinases (MMPs) and collagen degradation. Thus, chronic exposure of skin to UVB irradiation leads to histological changes consistent with aging, such as wrinkling, abnormal pigmentation, and loss of elasticity. We investigated the protective effect of the standardized green tea seed extract (GSE) on UVB-induced skin photoaging in hairless mice. MATERIALS/METHODS: Skin photoaging was induced by UVB irradiation on the back of Skh-1 hairless mice three times per week and UVB irradiation was performed for 10 weeks. Mice were divided into six groups; normal control, UVB irradiated control group, positive control (UVB + dietary supplement of vitamin C 100 mg/kg), GSE 10 mg/kg (UVB + dietary supplement of GSE 10 mg/kg), GSE 100 mg/kg (UVB + dietary supplement of GSE 100 mg/kg), and GSE 200 mg/kg (UVB + dietary supplement of GSE 200 mg/kg). RESULTS: The dietary supplement GSE attenuated UVB irradiation-induced wrinkle formation and the decrease in density of dermal collagen fiber. In addition, results of the antioxidant analysis showed that GSE induced a significant increase in antioxidant enzyme activity compared with the UVB irradiation control group. Dietary supplementation with GSE 200 mg/kg resulted in a significant decrease in expression of MMP-1, MMP-3, and MMP-9 and an increase in expression of TIMP and type-1 collagen. CONCLUSIONS: Findings of this study suggest that dietary supplement GSE could be useful in attenuation of UVB irradiation-induced skin photoaging and wrinkle formation due to regulation of antioxidant defense systems and MMPs expression.

• Journal of Life Science
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• v.22 no.1
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• pp.1-6
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• 2012

The present study examined the effects of consumption of Jeju ground water containing vanadium components on oxidative stress in obese (ob/ob) mice. Intake of Jeju ground water decreased the generation of oxidative stress induced-lipid peroxidation in the liver of ob/ob mice It also enhanced the enzymatic antioxidant defense system by increasing the protein expression and activity of superoxide dismutase, catalase, and glutathione peroxidase in liver tissues. Jeju ground water intake also upregulated the intracellular content of reduced glutathione. The induction of antioxidant enzyme expression by consumption of Jeju ground water was mediated by the erythroid transcription factor NF-E2 (Nrf2). Increased nuclear expression of phospho Nrf2 was observed in ob/ob mouse liver cells following ntake of Jeju ground water. These results suggest that consumption of Jeju ground water stimulated the antioxidant defense system in the livers of ob/ob mice via induction of Nrf2.

• Journal of Society of Preventive Korean Medicine
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• v.22 no.2
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• pp.77-107
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• 2018

Objectives : In present study, therefore, possible beneficial pharmacological activities of standard potato protein extracts (SPE) were observed on the mild diabetic obese mice. Methods : After end of 12 weeks of continuous oral administrations of three different dosages of SPE 400, 200 and 100 mg/kg, or metformin 250 mg/kg, analyzed the hepatoprotective, hypolipidemic, hypoglycemic, nephroprotective and anti-obesity effects, separately. In addition, liver antioxidant defense systems were additionally measured with lipid metabolism-related genes expressions and hepatic glucose-regulating enzyme activities for action mechanism. Results : All of diabetes and related complications including obesity were significantly inhibited by treatment of SPE 400, 200 and 100 mg/kg, dose-dependently, and they also dramatically normalized the hepatic lipid peroxidation and depletion of liver endogenous antioxidant defense system, the changes of the hepatic glucose-regulating enzyme activities, also changes of the lipid metabolism-related genes expressions including hepatic $AMPK{\alpha}1$ and $AMPK{\alpha}2$ mRNA expressions, dose-dependently. Especially, SPE 200 mg/kg constantly showed favorable inhibitory activities against type II diabetes and related complications as comparable to those of metformin 250 mg/kg in HFD mice, respectively. Conclusions : The present work demonstrated that SPE 400, 200 and 100 mg/kg showed favorable anti-diabetic and related complications including obesity refinement activities in HFD mice, through AMPK upregulation mediated hepatic glucose enzyme activity and lipid metabolism-related genes expression, antioxidant defense system and pancreatic lipid digestion enzyme modulatory activities.

• Journal of Microbiology and Biotechnology
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• v.22 no.11
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• pp.1557-1567
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• 2012

Glutathione reductase (GR, E.C. 1.6.4.2) is an important enzyme that reduces glutathione disulfide (GSSG) to a sulfydryl form (GSH) in the presence of an NADPH-dependent system. This is a critical antioxidant mechanism. Owing to the significance of GR, this enzyme has been examined in a number of animals, plants, and microbes. We performed a study to evaluate the molecular properties of GR (OsGR) from rice (Oryza sativa). To determine whether heterologous expression of OsGR can reduce the deleterious effects of unfavorable abiotic conditions, we constructed a transgenic Saccharomyces cerevisiae strain expressing the GR gene cloned into the yeast expression vector p426GPD. OsGR expression was confirmed by a semiquantitative reverse transcriptase polymerase chain reaction (semiquantitative RT-PCR) assay, Western-blotting, and a test for enzyme activity. OsGR expression increased the ability of the yeast cells to adapt and recover from $H_2O_2$-induced oxidative stress and various stimuli including heat shock and exposure to menadione, heavy metals (iron, zinc, copper, and cadmium), sodium dodecyl sulfate (SDS), ethanol, and sulfuric acid. However, augmented OsGR expression did not affect the yeast fermentation capacity owing to reduction of OsGR by multiple factors produced during the fermentation process. These results suggest that ectopic OsGR expression conferred acquired tolerance by improving cellular homeostasis and resistance against different stresses in the genetically modified yeast strain, but did not affect fermentation ability.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.510-517
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• 2016

This study was conducted to investigate the antioxidant and hepatoprotective effects of eriodictyol compound against hydrogen peroxide-induced oxidative stress in HepG2 cells by measuring expression levels of antioxidant enzymes, liver function index enzyme activities, and inhibitory effects against reactive oxygen species (ROS) production. HepG2 cell viability was assessed using 3-(4,5-dimethyl thiazole-2-yl)-2,5-diphenyl tetrazolium bromide assay. In the concentration range of $10{\sim}50{\mu}g/mL$, eriodictyol displayed over 98% cell viability in HepG2 cells. The effects of increased gene expression on hydrogen peroxide-induced oxidative stress were analyzed by monitoring antioxidant enzyme (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPx) gene expression levels using real-time PCR. Eriodictyol compound significantly increased gene expression levels of SOD, CAT, and GPx in a dose-dependent manner ($10{\sim}50{\mu}g/mL$). Hepatoprotective effects against hydrogen peroxide-induced oxidative stress were analyzed by monitoring glutamic oxaloacetic transaminase (GOT), lactate dehydrogenase (LDH), and gamma-glutamyl transferase (GGT) activities in HepG2 cell culture medium using a biochemistry analyzer. Eriodictyol compound significantly reduced GOT, LDH, and GGT activities in a dose-dependent manner in HepG2 cells. ROS level in HepG2 cells was analyzed by 2',7'-dichlorofluorescein fluorescence diacetate assay, and eriodictyol compound effectively reduced the intracellular ROS level in HepG2 cells. The results reveal that eriodictyol compound can be useful for development of effective antioxidant and hepatoprotective agents.

• Toxicological Research
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• v.23 no.3
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• pp.207-214
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• 2007

Chronic oxidative stress produced by exposure to environmental chemicals or pathophysiological states can lead animals to aging, carcinogenesis and degenerative diseases. Indirect antioxidative mechanisms, in which natural or synthetic agents are used to coordinately induce the expression of cellular antioxidant capacity, have been shown to protect cells and organisms from oxidative damages. Electrophile and free radical detoxifying enzymes, which were originally identified as the products of genes induced by cancer chemopreventive agents, are members of this protective system. The NFE2 family transcription factor Nrf2 was found to govern expression of these detoxifying enzymes, and screening for Nrf2-regulated genes has identified many gene categories involved in maintaining cellular redox potential and protection from oxidative damage as Nrf2 downstream genes. Further, studies using Nrf2-deficient mice revealed that these mutant mice showed more susceptible phenotypes towards exposure to environmental chemicals/carcinogens and in oxidative stress related disease models. With the finding that cancer chemopreventive efficacy of indirect antioxidants (enzyme inducers) is lost in the absence of Nrf2, a central role of Nrf2 in the antioxidative protective system has been firmly established. Promising results from cancer prevention clinical trials using enzyme inducers propose that pharmacological interventions that modulate Nrf2 can be an effective strategy to protect tissues from oxidative damage.

• Journal of Nutrition and Health
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• v.42 no.8
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• pp.673-681
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• 2009

Diabetes mellitus is a multifactorial disease. Particularly, diabetic nephropathy is a serious complication for diabetic patients, yet the precise mechanisms that underline the initial stage of diabetic renal inflammation remain unknown. However, oxidative stress induced by hyperglycemia in diabetes is implicated in diabetic renal disease. We hypothesized that dietary supplementation of antioxidants either VCE (0.5% VC + 0.5% VE) or Comb (0.5% VC + 0.5% VE + 2.5% N-acetylcysteine) improves acute diabetic renal inflammation through modulation of blood glucose levels and antioxidant and anti-inflammatory responses. Experimental animals (5.5 weeks old female ICR) used were treated with alloxan (180 mg/kg) once. When fasting blood glucose levels were higher than 250 mg/dL, mice were divided into 3 groups fed different levels of antioxidant supplementation, DM (diabetic mice fed AIN 93G purified rodent diet); VCE (diabetic mice fed 0.5% vitamin C and 0.5% vitamin E supplemented diet); Comb (diabetic mice fed 0.5% vitamin C, 0.5% vitamin E and 2.5% N-acetylcysteine supplemented diet), for 10 days and then sacrificed. Body weights were measured once a week and blood glucose levels were monitored twice a week. Lipid peroxidation products, thiobarbituric acid reacting substances were measured in kidney. NF-${\kappa}B$ activation was indirectly demonstrated by pI${\kappa}B$-${\alpna}$ and expressions of selective inflammatory and oxidative stress markers including antioxidant enzymes were also determined. Dietary antioxidant supplementation improved levels of blood glucose as well as kidney lipid peroxi-dation. Dietary antioxidant supplementation improved NF-${\kappa}B$ activation and protein expression of HO-1, but not mRNA expression levels in diabetic mice fed Comb diet. In contrast, the mRNA and protein expression of CuZnSOD was decreased in diabetic mice fed Comb diet. However, antioxidant supplementation did not improve mRNA and protein expressions of IL-$1{\beta}$ and MnSOD in diabetic mice. These findings demonstrate that acute diabetic renal inflammation was associated with altered inflammatory and antioxidant responses and suggest that antioxidant cocktail supplementation may have beneficial effects on early stage of diabetic nephropathy through modulation of blood glucose levels and antioxidant enzyme expressions.

• Journal of Haehwa Medicine
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• v.23 no.2
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• pp.5-13
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• 2015

Objectives : The anti-inflammatory and antioxidant effects of water extracts of Sasangja-tang(SSJ) and Gami-sasangja-tang(GSJ) were investigated. The effects of SSJ and GSJ were compared. Methods : We performed cell viability assay in HaCaT cells and RAW 264.7 cells using 3-(4,5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide(MTT) assay. We measured chemokines(regulated on activation normal T-cell expression and secreted ; RANTES/CCL5, interferon-inducible protein; IP-10/CXCL10, macrophage-derived chemokine; MDC/CCL22) in HaCat cells, also we measured cytokines (tumor necrosis factor-${\alpha}$; TNF-${\alpha}$, interleukin-6; IL-6) and nitric oxide(NO) production in RAW 264.7 cells using enzyme-linked immunosorbent assay(ELISA) and NO assay. Western blot assay was used to evaluate the expression for inducible nitric oxide synthase(iNOS) in RAW 264.7 cells. Results : SSJ and GSJ did not affect the cell viability at the concentrations treated ($0-800{\mu}g/ml$). As a result of SSJ and GSJ treatment in HaCat cells stimulated by TNF-${\alpha}$(10 ng/ml) and interferon(IFN)-${\gamma}$(10 ng/ml), the production of RANTES and IP-10 was inhibited significantly. However there was no significant difference in the secretion of MDC. And in RAW 264. 7 cells stimulated by lipopolysaccharide(LPS, $1{\mu}g/ml$), SSJ and GSJ treatment significantly inhibited the secretion of TNF-${\alpha}$ and IL-6 and the production of NO. The expression of iNOS was also decresed by SSJ and GSJ treatment in RAW 264. 7 cells. Compared with SSJ, GSJ was superior to SSJ in inhibition of RANTES, IP-10, TNF-${\alpha}$, IL-6 and NO production at the concentration of $200{\mu}g/ml$. Conclusion : Both SSJ and GSJ have anti-inflammatory and antioxidant effects. And GSJ has better effects than SSJ.

• Journal of Applied Biological Chemistry
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• v.48 no.1
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• pp.1-6
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• 2005

Analysis of chlorophyll (Chl) fluorescence implicated treatment of 40 mM NaCl decreased maximal photochemical efficiency of photosystem II (PSII) (Fv/Fm), actual quantum yield of PSII (${\Phi}_{PSII}$), and photochemical quenching (qP) in rice, but increased non-photochemical quenching (NPQ). Decreases in Fv/Fm, ${\Phi}_{PSII}$, and qP were significantly alleviated by $30\;{\mu}M$ jasmonic acid (JA), while NPQ increase was enhanced. Transcription levels of antioxidant isoenzyme genes were differentially modulated by NaCl treatment. Expression of cCuZn-SOD2 gene increased, while those of cAPXb, CATb, and CATc genes decreased. JA prevented salt-induced decrease of pCuZn-SOD gene expression, but caused greater decrease in mRNA levels of cAPXa and Chl_tAPX genes. Investigation of vacuolar $Na^+/H^+$ exchanger (NHX2) and 1-pyrroline-5-carboxylate synthetase (P5CS) gene expressions revealed transcription level of NHX2 gene was increased by JA, regardless of NaCl presence, while that of P5CS gene slightly increased only in co-presence of JA and NaCl. Unlike JA, ${\gamma}$-radiation rarely affected expressions of antioxidant isoenzyme, NHX2, and P5CS genes, except for increase in mRNA level of Chl_tAPX and decrease in that of pCuZn-SOD. These results demonstrate enhanced salt-tolerance in JA-treated rice seedlings may be partly due to high transcription levels of pCuZn-SOD, NHX2, and P5CS genes under salt stress.