• Nutrition Research and Practice
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• v.4 no.2
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• pp.93-98
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• 2010

Our previous study demonstrated that methanolic extract of Chrysanthemum zawadskii Herbich var. latilobum Kitamura (Compositae) has the potential to induce detoxifying enzymes such as NAD(P)H:(quinone acceptor) oxidoreductase 1 (EC 1.6.99.2) (NQO1, QR) and glutathione S-transferase (GST). In this study we further fractionated methanolic extract of Chrysanthemum zawadskii and investigated the detoxifying enzyme-inducing potential of each fraction. The fraction (CZ-6) shown the highest QR-inducing activity was found to contain (+)-(3S,4S,5R,8S)-(E)-8-acetoxy-4-hydroxy-3-isovaleroyloxy-2-(hexa-2,4-diynyliden)-1,6-dioxaspiro [4,5] decane and increased QR enzyme activity in a dose-dependent manner. Furthermore, CZ-6 fraction caused a dose-dependent enhancement of luciferase activity in HepG2-C8 cells generated by stably transfecting antioxidant response element-luciferase gene construct, suggesting that it induces antioxidant/detoxifying enzymes through antioxidant response element (ARE)-mediated transcriptional activation of the relevant genes. Although CZ-6 fraction failed to induce hepatic QR in mice over the control, it restored QR activity suppressed by $CCl_4$ treatment to the control level. Hepatic injury induced by $CCl_4$ was also slightly protected by pretreatment with CZ-6. In conclusion, although CZ-6 fractionated from methanolic extract of Chrysanthemum zawadskii did not cause a significant QR induction in mice organs such as liver, kidney, and stomach, it showed protective effect from liver damage caused by $CCl_4$.

• The Korean Journal of Mycology
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• v.30 no.2
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• pp.124-130
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• 2002

The inductions of phase II enzymes, such as NAD(P)H : quinone reductase (QR), glutathione S-transferase (GST), glutathione (GSH) level and the inhibition of polyamine metabolism were tested for the chemopreventive potentials of the extracts from the soybean fermented with Agrocybe cylindracea (AC) or Phellinus igniarius (PI). The soybean fermented with AC or PI was potent inducer of QR activity in murine hepatoma Hepa1c1c7 cells. GST activities of the extracts from soybean fermented with AC or PI were higher than that of the extract from soybean not fermented with basidiomycetes. In addition, GSH levels of the extracts from soybean fermented with AC or PI were increased about 1.2 fold or 1.4 fold, respectively. In addition, proliferation of Acanthamoeba castellanii in a broth medium was inhibited by the extracts from soybean fermented with AC or PI at the both concentration of 20 and 40 mg/3 ml. These results suggest that soybean fermented with AC or PI may have chemopreventive potentials by inducing QR activity, increasing GSH and GST levels and inhibiting polyamine metabolism.

• Journal of Nutrition and Health
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• v.29 no.1
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• pp.22-31
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• 1996

The purpose of this study was to investigate the effect of vitamin E and selenium on the antioxidative defense mechanism in the liver of streptozotocin(STZ)-induced diabetic rats. Sprague-Dawley male rats(120$\pm$10gm) were randomly assigned to one control and five STZ-diabetic groups. Diabetic groups were classified to STZ-0E (vitamin E free diet), STZ-40E(40mg vitamin E/kg of diet), STZ-400E(400mg vitamin E/kg of diet), STZ-S(0.5ppm Se/kg of diet) and STZ-400ES(400mg vitamin E and 0.5ppm Se/kg of diet) according to the level of vitamin E and selenium supplementation. Diabetes was experimentally induced by intravenous adminstration of 55mg/kg of STZ in citrate buffer(pH 4.3) after 4-weeks feedng of six experimental diets. Animals were sacrificed at the 4th day of diabetic states. Activities of the serum glutamic oxaloacetate transaminase(GOT) and the glutaminc pyruvate transaminase(GPT) in STZ-0E, STZ-40E and STZ-S rats were higher than those of control. Liver xanthine oxidase activities were similar to serum GOT and GPT. Liver superoxide dismutase(SOD) activities were higher in STZ-0E and STZ-40E groups by 33%, 22%, respectively than that of control. Glutathione S-transferase(GST) activities of liver were similar to GSH-Px activities. The contents of vitamin E in liver tissue were significantly lower STZ-0E, STZ-40E and STZ-S groups by 50%, 36%, 45% than that of control. Reduced glutathione(GSH) contents of liver were lower STZ-0E, STZ-40E, STZ-400E, STZ-S and STZ-400ES groups by 57%, 51%, 19%, 18%, 12% than that of control. Lipid peroxide values (LPO) in liver were higher 5.6, 2.3 and 2.3 times in STZ-0E, STZ-40E and STZ-S group than that of control. The present results indicate that STZ-induced diabetic rats are more sensitive to oxidative stress, leading to the acceleration of lipid peroxidation process, which can be more accelerated by feeding the low level of dietary vitamin E. In the coincident supplementation of high dietary vitamin E and selenium antioxidative enzymes activities and physiolosical antioxidants were increased more than those of the separate supplementation of vitamin E or selenium. Therefore, dietary vitamin E and selenium reduced peroxidative damage of tissue, promoting antioxidative defense mechanism against lipid peroxidation by diabetes.

• Parasites, Hosts and Diseases
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• v.56 no.2
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• pp.135-145
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• 2018

Due to the critical location and physiological activities of the retinal pigment epithelial (RPE) cell, it is constantly subjected to contact with various infectious agents and inflammatory mediators. However, little is known about the signaling events in RPE involved in Toxoplasma gondii infection and development. The aim of the study is to screen the host mRNA transcriptional change of 3 inflammation-related gene categories, PI3K/Akt pathway regulatory components, blood vessel development factors and ROS regulators, to prove that PI3K/Akt or mTOR signaling pathway play an essential role in regulating the selected inflammation-related genes. The selected genes include PH domain and leucine- rich-repeat protein phosphatases (PHLPP), casein kinase2 (CK2), vascular endothelial growth factor (VEGF), pigment epithelium-derived factor (PEDF), glutamate-cysteine ligase (GCL), glutathione S-transferase (GST), and NAD(P)H: quinone oxidoreductase (NQO1). Using reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), we found that T. gondii up-regulates PHLPP2, $CK2{\beta}$, VEGF, GCL, GST and NQO1 gene expression levels, but down-regulates PHLPP1 and PEDF mRNA transcription levels. PI3K inhibition and mTOR inhibition by specific inhibitors showed that most of these host gene expression patterns were due to activation of PI3K/Akt or mTOR pathways with some exceptional cases. Taken together, our results reveal a new molecular mechanism of these gene expression change dependent on PI3K/Akt or mTOR pathways and highlight more systematical insight of how an intracellular T. gondii can manipulate host genes to avoid host defense.

• Asian-Australasian Journal of Animal Sciences
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• v.33 no.7
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• pp.1167-1179
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• 2020

Objective: This study was conducted to fathom the underlying mechanisms of nutrition intervention and redox sensitive transcription factors regulated by Antrodia cinnamomea fermented product (FAC) dietary supplementation in broiler chickens. Methods: Four hundreds d-old broilers (41±0.5 g/bird) assigned to 5 groups were examined after consuming control diet, or control diet replaced with 5% wheat bran (WB), 10% WB, 5% FAC, and 10% FAC. Liver mRNA expression of antioxidant, inflammatory and lipid metabolism pathways were analyzed. Prostaglandin E2 (PGE₂) concentration in each group were tested in the chicken peripheral blood mononuclear cells (cPBMCs) of 35-d old broilers to represent the stress level of the chickens. Furthermore, these cells were stimulated with 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) and lipopolysaccharide (LPS) to evaluate the cell stress tolerance by measuring cell viability and oxidative species. Results: Heme oxygenase-1, glutathione S-transferase, glutamate-cysteine ligase, catalytic subunit, and superoxide dismutase, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that regulates the above antioxidant genes were all up-regulated significantly in FAC groups. Reactive oxygen species modulator protein 1 and NADPH oxygenase 1 were both rather down-regulated in 10% FAC group as comparison with two WB groups. Despite expressing higher level than control group, birds receiving diet containing FAC had significantly lower expression level in nuclear factor-kappa B (NF-κB) and other genes (inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1β, nucleotide-binding domain, leucine-richcontaining family, pyrin domain-containing-3, and cyclooxygenase 2) involving in inflammatory pathways. Additionally, except for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that showed relatively higher in both groups, the WB, lipoprotein lipase, Acetyl-CoA carboxylase, fatty acid synthase, fatty acid binding protein, fatty acid desaturase 2 and peroxisome proliferator-activated receptor alpha genes were expressed at higher levels in 10% FAC group. In support of above results, promoted Nrf2 and inhibited NF-κB nuclear translocation in chicken liver were found in FAC containing groups. H₂O₂ and NO levels induced by LPS and AAPH in cPBMCs were compromised in FAC containing diet. In 35-d-old birds, PGE₂ production in cPBMCs was also suppressed by the FAC diet. Conclusion: FAC may promote Nrf2 antioxidant pathway and positively regulate lipid metabolism, both are potential inhibitor of NF-κB inflammatory pathway.

• Journal of Microbiology and Biotechnology
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• v.20 no.9
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• pp.1331-1338
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• 2010

This study was designed to investigate the potentially protective effects of Curcuma longa Linn. extract (CLE) on carbon tetrachloride ($CCl_4$)-induced hepatotoxicity in rats. Male Sprague-Dawley rats were pretreated with 50 or 100mg/kg of CLE or 100mg/kg of butylated hydroxytoluene(BHT) for 14 days before $CCl_4$ administration. In addition, the CLE control group was pretreated with 100mg/kg CLE for only 14 days. Three hours after the final treatment, a single dose of $CCl_4$ (20mg/kg) was administrated intraperitoneally to each group. After the completion of this phase of the experiment, food and water were removed 12 h prior to the next step. The rats were then anesthetized by urethane and their blood and liver were collected. It was observed that the aspartate aminotransferase and alanine aminotransferase activities of the serum, and the hepatic malondialdehyde levels had significantly decreased in the CLE group when compared with the $CCl_4$-treated group. The antioxidant activities, such as superoxide dismutase, catalase, and glutathione peroxidase activities, in addition to glutathione content, had increased considerably in the CLE group compared with the $CCl_4$-treated group. Phase II detoxifying enzymes, such as glutathione S-transferase, were found to have significantly increased in the CLE group as opposed to the $CCl_4$-treated group. The content of Nrf2 was determined by Western blot analysis. Pretreated CLE increased the level of nuclear translocated Nrf2, and the Nrf2 then increased the activity of the antioxidant and phase II detoxifying enzymes. These results indicate that CLE has protective effects against $CCl_4$-induced hepatotoxicity in rats, via activities of antioxidant and phase II detoxifying enzymes, and through the activation of nuclear translocated Nrf2.

• BMB Reports
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• v.49 no.7
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• pp.382-387
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• 2016

Reactive oxygen species generated under oxidative stress are involved in neuronal diseases, including ischemia. Glutathione S-transferase pi (GSTpi) is a member of the GST family and is known to play important roles in cell survival. We investigated the effect of GSTpi against oxidative stress-induced hippocampal HT-22 cell death, and its effects in an animal model of ischemic injury, using a cell-permeable PEP-1-GSTpi protein. PEP-1-GSTpi was transduced into HT-22 cells and significantly protected against H2O2-treated cell death by reducing the intracellular toxicity and regulating the signal pathways, including MAPK, Akt, Bax, and Bcl-2. PEP-1-GSTpi transduced into the hippocampus in animal brains, and markedly protected against neuronal cell death in an ischemic injury animal model. These results indicate that PEP-1-GSTpi acts as a regulator or an antioxidant to protect against oxidative stress-induced cell death. Our study suggests that PEP-1-GSTpi may have potential as a therapeutic agent for the treatment of ischemia and a variety of oxidative stress-related neuronal diseases.

• Journal of Life Science
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• v.15 no.1 s.68
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• pp.118-123
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• 2005

For the expression in Saccharomyces cerevisiae, Bacillus stearothermophilus cyclodextrin glucano­transferase gene (cgtS) in pCGTS (4.8 kb) was subcloned into the surface expression vector, pYD1 (GALl promoter). The constructed plasmid, pYDCGT (7.2 kb) was introduced into S. cerevisiae EBY100 cells, and then yeast transformants were selected on the synthetic defined media lacking tryptophan. The formation of cyclodextrin (CD) was confirmed with active staining of culture broth of transformant grown on starch medium. Enzymatic reaction products with respect to the culture time and the reaction time were examined by TLC analysis. The results indicated that the enzyme activity was exhibited after 12 h cultivation and CD was produced after 10min of enzymatic reaction. When the surface-engineered yeast cells were cultured on galactose medium, maximum activities of CGTase were about 21.3 unit/l and 16.5 unit/l at $25^{\circ}C\;and\;30^{\circ}C$, respectively. The plasmids stability showed about $80\%\;even\;at\;25^{\circ}C\;and\;30^{\circ}C$.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3687-3693
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• 2012

Objective: The current meta-analysis was performed to address a more accurate estimation of the association between glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and risk of gastric cancer (GC), which has been widely reported with conflicting results. Methods: A comprehensive literature search was conducted to identify all the relevant studies. Fixed or random effect models were selected based on the heterogeneity test. Publication bias was estimated using Begg's funnel plots and Egger's regression test. Results: A total of 20 studies containing 2,821 GC cases and 6,240 controls were finally included in the analyses. Overall, no significant association between GSTP1 polymorphism and GC risk was observed in worldwide populations. However, subgroup analysis stratified by ethnicity showed that GSTP1 polymorphism was significantly associated with increased risk of GC in Asians (G vs. A, OR = 1.273, 95%CI=1.011-1.605; GG vs. AA, OR=2.103, 95%CI=1.197-3.387; GG vs. AA+AG, OR =2.103, 95%CI=1.186-3.414). In contrast, no significant association was found in Caucasians in any genetic models, except for with AG vs. AA (OR=0.791, 95%CI=0.669-0.936). Furthermore, the GSTP1 polymorphism was found to be significantly associated with GC in patients with H. pylori infection and in those with a cardiac GC. Subgroup analysis stratified by Lauren's classification and smoking status showed no significant association with any genetic model. No studies were found to significantly influence the pooled effects in each genetic mode, and no potential publication bias was detected. Conclusion: This meta-analysis suggested that the GSTP1 polymorphism might be associated with increased risk of GC in Asians, while GSTP1 heterozygote genotype seemed to be associated with reduced risk of GC. Since potential confounders could not be ruled out completely, further studies are needed to confirm these results.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.167-167
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• 2017

Our previous study for developing seeds of Iksan 526 (I.526), an inbred line of resveratrol-producing transgenic rice line, showed that, in 20 days after heading (DAH) seeds, resveratrol was almost saturated and accumulation of piceid was highest though the expression of Arachis hypogaea resveratrol synthase 3 (AhRS3, GenBank DQ124938) was highest in 31 DAH seeds. In this study, it was investigated how the overexpression of AhRS3 affects phenylpropanoid pathway genes. p-Coumaroyl-CoA is derived from phenylpropanoid pathway and used as a substrate of AhRS3 reaction for resveratrol production. In 6, 13, 20, 31 and 41 (45 for Dongjin) DAH seeds of I526 and Dongjin, a wild type of I.526, respectively, the expression pattern of phenylpropanoid pathway genes, including phenylalanine ammonia-lyase (PAL: LOC_Os02g41630.2, LOC_Os04g43760.1), cinnamate 4-hydroxylase (C4H: LOC_Os05g25640.1), 4-coumarate-CoA ligase (4CL: LOC_Os02g08100.1), cinnamoyl-CoA reductase (CCR: LOC_ Os09g25150.1, LOC_Os08g34280.1), hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyl transferase (HCT: LOC_Os04g42250.2, LOC_Os02g39850.1) and cinnamyl alcohol dehydrogenase (CAD: LOC_Os02g09490.1), was examined using real time (RT)-PCR. Compared to developing seeds of Dongjin, RT-PCR results showed that the expression pattern of phenylpropanoid pathway genes was modified in developing seeds of I.526. In most genes, except for CAD, of I.526 developing seeds, the gene expression was highest in 20 DAH corresponding to biosynthesis of resveratrol and piceid, i.e. the expression of phenylpropanoid pathway genes was gradually increased by 20 DAH and decreased as seeds develop. Especially, in Dongjin, the highest expression of PALs and 4CL was in 6 DAH and their expression was gradually decreased as seeds develop. These genes expression data also exhibited that, in developing seeds of I.526, phenylpropanoid pathway genes were slightly or significantly (in some genes) upregulated compared to Dongjin. Therefore, the overexpression of AhRS3 changed the expression pattern of phenylpropanoid pathway genes in I.526 developing seeds and this modification for gene expression is closely related to biosynthesis of resveratrol and piceid.