• Archives of Pharmacal Research
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• v.28 no.3
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• pp.249-268
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• 2005

Drug metabolizing enzymes (DMEs) play central roles in the metabolism, elimination and detoxification of xenobiotics and drugs introduced into the human body. Most of the tissues and organs in our body are well equipped with diverse and various DMEs including phase I, phase II metabolizing enzymes and phase III transporters, which are present in abundance either at the basal unstimulated level, and/or are inducible at elevated level after exposure to xenobiotics. Recently, many important advances have been made in the mechanisms that regulate the expression of these drug metabolism genes. Various nuclear receptors including the aryl hydrocarbon receptor (AhR), orphan nuclear receptors, and nuclear factor-erythoroid 2 p45-related factor 2 (Nrf2) have been shown to be the key mediators of drug-induced changes in phase I, phase II metabolizing enzymes as well as phase III transporters involved in efflux mechanisms. For instance, the expression of CYP1 genes can be induced by AhR, which dimerizes with the AhR nuclear translocator (Arnt) , in response to many polycyclic aromatic hydrocarbon (PAHs). Similarly, the steroid family of orphan nuclear receptors, the constitutive androstane receptor (CAR) and pregnane X receptor (PXR), both heterodimerize with the ret-inoid X receptor (RXR), are shown to transcriptionally activate the promoters of CYP2B and CYP3A gene expression by xenobiotics such as phenobarbital-like compounds (CAR) and dexamethasone and rifampin-type of agents (PXR). The peroxisome proliferator activated receptor (PPAR), which is one of the first characterized members of the nuclear hormone receptor, also dimerizes with RXR and has been shown to be activated by lipid lowering agent fib rate-type of compounds leading to transcriptional activation of the promoters on CYP4A gene. CYP7A was recognized as the first target gene of the liver X receptor (LXR), in which the elimination of cholesterol depends on CYP7A. Farnesoid X receptor (FXR) was identified as a bile acid receptor, and its activation results in the inhibition of hepatic acid biosynthesis and increased transport of bile acids from intestinal lumen to the liver, and CYP7A is one of its target genes. The transcriptional activation by these receptors upon binding to the promoters located at the 5-flanking region of these GYP genes generally leads to the induction of their mRNA gene expression. The physiological and the pharmacological implications of common partner of RXR for CAR, PXR, PPAR, LXR and FXR receptors largely remain unknown and are under intense investigations. For the phase II DMEs, phase II gene inducers such as the phenolic compounds butylated hydroxyanisol (BHA), tert-butylhydroquinone (tBHQ), green tea polyphenol (GTP), (-)-epigallocatechin-3-gallate (EGCG) and the isothiocyanates (PEITC, sul­foraphane) generally appear to be electrophiles. They generally possess electrophilic-medi­ated stress response, resulting in the activation of bZIP transcription factors Nrf2 which dimerizes with Mafs and binds to the antioxidant/electrophile response element (ARE/EpRE) promoter, which is located in many phase II DMEs as well as many cellular defensive enzymes such as heme oxygenase-1 (HO-1), with the subsequent induction of the expression of these genes. Phase III transporters, for example, P-glycoprotein (P-gp), multidrug resistance-associated proteins (MRPs), and organic anion transporting polypeptide 2 (OATP2) are expressed in many tissues such as the liver, intestine, kidney, and brain, and play crucial roles in drug absorption, distribution, and excretion. The orphan nuclear receptors PXR and GAR have been shown to be involved in the regulation of these transporters. Along with phase I and phase II enzyme induction, pretreatment with several kinds of inducers has been shown to alter the expression of phase III transporters, and alter the excretion of xenobiotics, which implies that phase III transporters may also be similarly regulated in a coordinated fashion, and provides an important mean to protect the body from xenobiotics insults. It appears that in general, exposure to phase I, phase II and phase III gene inducers may trigger cellular 'stress' response leading to the increase in their gene expression, which ultimately enhance the elimination and clearance of these xenobiotics and/or other 'cellular stresses' including harmful reactive intermediates such as reactive oxygen species (ROS), so that the body will remove the 'stress' expeditiously. Consequently, this homeostatic response of the body plays a central role in the protection of the body against 'environmental' insults such as those elicited by exposure to xenobiotics.

• Journal of the Korean Institute of Landscape Architecture
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• v.45 no.2
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• pp.51-59
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• 2017

This study evaluated the drought tolerance of Liriope platyphylla F.T.Wang & T.Tang, Dendranthema zawadskii var. lucidum (Nakai) J.H.Park, Hosta longipes (Franch. & Sav.) Matsum., Sedum sarmentosum Bunge and Zoysia japonica Steud. for an extensive green roof. In order to assess drought tolerance of green roof plants, several criteria were measured such as volumetric water content, leaf and soil moisture potential, chlorophyll a and b, chlorophyll fluorescence, photosynthesis, stomatal conductance, transpiration rate and antioxidants. The results of the drought tolerance measurement of green roof plants focused on the gradually withering of plants from lack of volumetric water content. D. zawadskii was the first to show an initial wilting point, followed by Z. japonica, H. longipes and L. platyphylla in order while S. sarmentosum showed no withering. It was concluded that H. longipes, L. platyphylla and S. sarmentosum were highly drought tolerant plants able to survive over three weeks. Furthermore, chlorophyll a and b were divided into two types: Type I, which kept regular content from the beginning to the middle of the period and suddenly declined, like H. longipes and Z. japonica; and Type II, which showed low content at the beginning, sharply increased at the middle stage and decreased, like D. zawadskii, L. platyphylla and S. sarmentosum. Volumetric water content and the amount of evapotranspiration consistently declined in all plant species. The analysis of chlorophyll fluorescence results that S. sarmentosum, which had relatively high drought tolerance, was the last to decline, while Z. japonica and S. sarmentosum withered after rapid reduction. At first, photosynthesis, stomatal conductance and transpiration rate showed high activity, but they lowered as the plant body closed stomata owing to the decrease in volumetric water content. Measuring antioxidants showed that when drought stress increased, the amount of antioxidants grew as well. However, when high moisture stress was maintained, this compound was continuously consumed. Therefore, the variation of antioxidants was considered possible for use as one of the indicators of drought tolerance evaluation.

• Journal of Preventive Medicine and Public Health
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• v.39 no.2
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• pp.130-134
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• 2006

Objectives : Oxidative DNA damage is a known risk factor of lung cancer. The glutathione peroxidase (GPX) antioxidant enzyme that reduces hydrogen peroxide and lipid peroxides plays a significant role in protecting cells from the oxidative stress induced by reactive oxygen species. The aim of this case-control study was to investigate effects of oxidative stress and genetic polymorphisms of the GPX1 genes and the interaction between them in the carcinogenesis of lung cancer. Methods : Two hundreds patients with lung cancer and 200 age- and sex-matched controls were enrolled in this study. Every subject was asked to complete a questionnaire concerning their smoking habits and their environmental exposure to PAHs. The genotypes of the GPX1 and 8-oxoguanine glycosylase 1 (hOGG1) genes were examined and the concentrations of urinary hydroxypyrene (1-OHP), 2-naphthol and 8-hydroxydeoxyguanosine (8-OH-dG) were measured. Results : Cigarette smoking was a significant risk factor for lung cancer. The levels of urinary 8-OH-dG were higher in the patients (p<0.001), whereas the urinary 1-OHP and 2-naphthol levels were higher in the controls. The GPX1 codon 198 polymorphism was associated with an increased risk of lung cancer. Individuals carrying the Pro/Leu or Leu/Leu genotype of GPX1 were at a higher risk for lung cancer (adjusted OR=2.29). In addition, these individuals were shown to have high urinary 8-OH-dG concentrations compared to the individuals with the GPX1 Pro/Pro genotype. On the other hand, the polymorphism of the hOGG1 gene did not affect the lung cancer risk and the oxidative DNA damage. Conclusions : These results lead to a conclusion that individuals with the GPX1 Pro/Leu or Leu/Leu genotype would be more susceptible to the lung cancer induced by oxidative stress than those individuals with the Pro/Pro genotype.

• Korean Journal of Food Science and Technology
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• v.46 no.5
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• pp.641-647
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• 2014

In this study, we evaluated the effect of Capsosiphon fulvescens extract (CFE) and its active compound, pheophorbide A (PhA), on diabetic kidney failure. Diabetes mellitus (DM) was induced by a single intraperitoneal injection of streptozotocin (STZ; 40 mg/kg body weight (BW)). After a week, the rats were orally administered CFE (4 and 20 mg/kg BW) or PhA (0.2 mg/kg BW) once a day for 9 weeks. After scarification, renal tissue samples were collected for biochemical and histochemical analyses. Our study showed that the treatment with CFE and PhA significantly decreased lipid peroxidation level and the activities of glutathione peroxidase and glutathione-S-transferase (p<0.05), but it increased glutathione level and the activities of glutathione reductase, superoxide dismutase, and catalase in the renal tissues (p<0.05). The CFE- and PhA-treated rats with DM showed improved histochemical appearance and decreased abnormal glycogen accumulation. Therefore, we suggest that PhA-containing CFE could exert renal protective effects against STZ-induced oxidative stress.

• Journal of Life Science
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• v.31 no.9
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• pp.818-826
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• 2021

5-Aminolevulinic acid phosphate (5-ALA-p) is a substance obtained by eluting 5-ALA (a natural delta amino acid) with aqueous ammonia, adding phosphoric acid to the eluate, and then adding acetone to confer properties suitable for use in photodynamic therapy applications. However, its pharmacological efficacy, including potential mechanisms of antioxidant and anti-inflammatory reactions, remains unclear. This study aimed to investigate the effects of 5-ALA-p on oxidative and inflammatory stresses in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our data showed that 5-ALA-p significantly inhibited excessive phagocytic activity via LPS and attenuated oxidative stress in LPS-treated RAW 264.7 cells. Furthermore, 5-ALA-p improved mitochondrial biogenesis reduced by LPS, suggesting that 5-ALA-p restores mitochondrial damage caused by LPS. Additionally, 5-ALA-p significantly suppressed the release of nitric oxide (NO) and pro-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, which are associated with the inhibition of inducible NO synthase and respective cytokine expression. Furthermore, 5-ALA-p reduced the nuclear translocation of nuclear factor-kappa B (NF-κB) and inhibited phosphorylation of mitogen-activated protein kinases (MAPKs), indicating that the anti-inflammatory effect of 5-ALA-p is mediated through the suppression of NF-κB and MAPK signaling pathways. Based on these results, 5-ALA-p may serve as a potential candidate to reduce inflammation and oxidative stress.

• Korean Journal of Ecology and Environment
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• v.56 no.4
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• pp.320-329
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• 2023

Cadmium (Cd), a heavy metal found in the aquatic environment, accumulates in organisms through the food chain. In the study, we investigated the survival rates, measurement of body Cd levels, and expression analysis of the stress response genes (Heat shock protein 70: HSP70 and Heat shock protein 60: HSP60) and antioxidant enzyme Glutathione S-Transferases (GST) on benthic oligochaete worm Tubifex tubifex exposed three concentrations of Cd, to analyze the bioaccumulation and changes of stress gene expressions to exposure toxicity of the Cd-spiked sediment. Survival rates of T. tubifex exposed to the Cdspiked sediment were 93% at 0.4 mg kg^-1 Cd, 96% at 1.87 mg kg^-1 Cd, and 93% at 6.09 mg kg^-1 Cd for 10 days. Cd concentration in the body of T. tubifex was higher than that in the sediment. After Cd exposures for 10 days, the body Cd levels were 18.4 mg kg^-1, 13.06 mg kg^-1, and 79.11 mg kg^-1 at exposed three concentrations of Cd, respectively. Upregulation of HSP70 gene expression was observed at all concentrations of exposed Cd as a time-dependent manner, whereas transcriptional expression of the HSP60 gene increased as a timedependent manner in T. tubifex exposed to the relative high concentration (6.09 mg kg^-1) of Cd. However, GST gene expression increased on day 1 at all concentrations after Cd exposures, and then downregulated until 10 days. These results indicate to ecotoxicological and molecular effects in benthic oligochaete worm T. tubifex to Cd-spiked sediment and provide the basic information for the utilization of environmental toxicity assessment using the T. tubifex as a aquatic pollution indicator species.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.1
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• pp.42-56
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• 2005

Hyperlipidemia is one of the risk factors for coronary artery disease. Despite of epidemiological evidence that tea consumption is associated with the reduced risk of coronary heart disease, experimental studies designed to show that drinking tea affects blood lipid concentration or oxidative stress have been unsuccessful. The purpose of this study was to investigate whether functional tea (three servings/day) supplement with medical nutrition therapy (MNT) lead to a beneficial outcomes in mildly hyperlipidemic adults. From February to October, 2003, the 43 hyperlipidemic (23 men, 20 women) subjects (total cholesterol$\geq$200 mg/dL or triglyceride$\geq$150 mg/dL) admitted to K Medical Center were studied. Subjects were randomly divided into 3 groups; placebo tea (PT), half dose of functional tea (HFT), full dose of functional tea (FFT). During 12 weeks of study period, the subjects were given placebo or functional tea daily with MNT. Anthropometric measurements, blood chemical analysis including lipid levels, total superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, and dietary assessment were carried out at the beginning and end of experiment. The effects of functional tea were compared with the placebo in randomized clinical trial study. The placebo was prepared to match with the functional tea in color and taste. After the 12 weeks of MNT, the subjects had regular and balanced meal pattern. Consumption of foods high in cholesterol and saturated fat, salty foods, fried foods, and instant foods decreased significantly in all three groups (p<0.05). Intake of energy and cholesterol also decreased (p<0.05). Drinking three servings per day (390 mL/day) of functional tea significantly reduced the levels of blood triglyceride (HFT, 42.5%; FFT, 29.4%), total cholesterol (HFT, 8.5%; FFT, 13.7%), and atherogenic index (HFT, 14.6%; FFT, 21.7%). Whereas no changes were found in the LDL-, HDL-cholesterollevels, and LDL/HDL ratio. Plasma homocysteine (Hcy) concentration decreased significantly (p<0.05) in functional tea groups (HFT, 14.9%; FFT, 14.1%). SOD increased significantly (p<0.05) in HFT (8.3%). GSH-Px increased significantly (p<0.05) in FFT (12.8%). In conclusion, the MNT improved the dietary habits, in addition, functional tea supplement decreased blood lipid levels and Hcy, and increased SOD and GSH-Px levels. These results indicate that functional tea consumption may decrease the risk of cardiovascular disease via improving blood lipid levels and antioxidant status.

• Journal of Food Hygiene and Safety
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• v.26 no.3
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• pp.260-265
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• 2011

Plantago asiatica L. (P. asiatica) has been used as one of the popular folk medicines in Asia for human health care practices. Various activities of P. asiatica have been reported, such as anti-oxidant, anti-glycation, anti-inflammatory and hepatoprotective activity. Therefore, the potential of P. asiatica to reduce oxidative stress has been studied in several ways for over 20 years, especially at liver and kidney. However no investigation has been reported revealing its protective effect on prostate. Method: Treatment of P. asiatica leaf ethanolic extract (PLE) (1 g/kg body weight (b.w.), 2 g/kg b.w., or 4 g/kg b.w.) were given separately to animals for pretreatment once per day for 7 days, and on the seventh day ferric nitrilotriacetate (Fe-NTA; 0.24 mmol Fe/kg b.w.), which is known as an oxidative stress-inducer at prostate, was administrated by i.p to negative control group. At the end of the study period, dissection was carried out for detecting the prostate protective effect of PLE. Result: Fe-NTA-treated animals produced reactive oxygen species (ROS) resulting in depletion of antioxidant biomaker, such as glutathione (GSH), glutathione reductase (GR), and glutathione s-transferase (GST) and increase of lipid peroxidation in prostate. However, PLE pretreatment resulted in an increase in the GSH, GST and GR levels concentration dependent manner and in an significant decrease in the levels of lipid peroxidation. Conclusion: Our data suggest that PLE may be effective in protecting oxidative stress-induced damage of prostate, and PLE may be an chemopreventive agent against Fe-NTA-mediated prostate oxidative damage.

• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.2
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• pp.321-326
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• 2011

The aim of the present study was to investigate antihyperglycemic effect of Gleditschiae Spina (GS) in streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic rats. The rats were divided into four groups: normal control (NC), diabetic control (DC), diabetic rats supplemented with acarbose (AC, 4 mg/kg), and with GS ethanol extracts (GSE, 50 mg/kg). Weekly fasting blood glucose (FBG) for 10 weeks and oral glucose tolerance test (OGTT) at 10th week were monitored using glucose oxidase-peroxidase reactive strips. The FBG level was significantly reduced in AC group after 8 weeks and in GSE group at the end of period. The AUCs for the glucose response from OGTT and blood glucose level after sacrifice were significantly lower in the AC and GSE groups than the DC group. GSE supplementation significantly increased plasma total radical-trapping antioxidant potential (TRAP) in STZ-NA-induced diabetic rats, compared with DC group. The present study indicates that GSE could ameliorate type 2 diabetes and be comparable to acarbose, a standard hypoglycemic drug. Also, we suggest that GSE may possess antioxidant activity against the STZ-NA-induced oxidative stress.

• Journal of the Korean Society of Food Science and Nutrition
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• v.42 no.6
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• pp.869-876
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• 2013

To develop functional products based on black garlic, a black garlic extract (BG) of 7 brix, a gaeddongssuk extract (GS) of 0.7 brix and two types of mixtures (MBS-I, black garlic 7 brix : gaeddongssuk 0.7 brix; MBS-II, black garlic 14 brix : gaeddongssuk 1.4 brix, 93:7, v/v) were supplemented to rats training on a treadmill for 4 weeks. Body weight from the training did not decrease during the experimental period. Serum albumin content significantly increased in the groups fed an experimental diet compared to the control. The BUN content significantly decreased in BG and MBS-II groups compared to the control. AST and ALP activities significantly decreased in the groups fed an experimental diet compared to the control. Serum triglyceride and total cholesterol levels in MBS-I and MBS-II groups significantly decreased compared to the control. Lipid levels in the serum and liver tissue were not significantly different between the MBS-I and MBS-II groups. The lipid peroxide content in the serum and liver tissue was significantly reduced in the groups fed all extracts compared to the control; the serum and liver lipid contents was lowest in the MBS-I and MBS-II groups, respectively. Hepatic catalase activity in the GS and MBS groups increased by 1.8~2.3 times compared to the control. SOD and GSH-px activities significantly increased from treatment with the extracts by 1.3~1.5 times and 1.2~1.7 times, respectively. These results indicate that a mixture of BG and GS extracts has higher biological activity than a single supplementation of BG or GS extract. Therefore, the addition of gaeddongssuk to black garlic (MBS-I and MBS-II) is effective as a defense material against oxidative stress. MBS-I may be especially effective for its biological activities.