• 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.

• Korean Journal of Food Science and Technology
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• v.49 no.4
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• pp.430-437
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• 2017

The protective effect of Pteridium aquilinum on high glucose-induced cytotoxicity was examined in vitro to investigate the relationship between diabetic condition and neuronal dysfunction. The ethyl acetate fraction of P. aquilinum (EFPA), with total phenolic content of 265.08 mg gallic acid equivalent/g, showed higher 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)/2,2-diphenyl-1-picrylhydrazyl radical scavenging activities and lipid peroxidation inhibitory effect than any other fraction. In addition, EFPA showed a significant reduction in the inhibitory effect on ${\alpha}$-glucosidase activity ($IC_{50}$ value=$205.26{\mu}g/mL$) compared to the acarbose positive control. The anti-oxidative effect in PC12 cells, protective effects on high glucose-induced oxidative stress in neuronal cells, and neurotoxicity were measured using 2',7'-dichlorofluorescin diacetate, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide, and lactate dehydrogenase assays, respectively. EFPA showed conspicuous inhibitory effect on cellular reactive oxygen species production and neuronal cell apoptosis. Finally, kaempferol-3-glucoside was identified as the main phenolic compound of EFPA using high performance liquid chromatography.

• Korean Journal of Food Science and Technology
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• v.39 no.2
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• pp.209-216
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• 2007

The present study investigated anti-oxidative and anti-inflammatory activity of glycoprotein isolated from Morus Indica Linne (MIL glycoprotein). We found that MIL glycoprotein has a molecular weight of 32 kD and consists of carbohydrate (40.03%) and protein (59.97%), and that it has a strong scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical $({\cdot}OH)$, and superoxide anion $(O_2{\cdot}\;^-)$ radicals. In addition, MIL glycoprotein had a stable character and an optimal DPPH radical scavenging activity in the alkaline and neutral pH solution, and up to at 105. However, the results indicated that it has a minimal scavenging activity in the metal ionic solution ($Ca^{2+}$, $Mn^{2+}$, and $Mg^{2+}$) in the presence of EDTA. In addition, we further investigated whether MIL glycoprotein scavenges oxygen radicals and blocks inflammation-related signals in the bisphenol A (BPA)-stimulated Raw 264.7 cells. The results in this study showed that it has a character to scavenge the productions of reactive oxygen species (ROS) and nitric oxide (NO) dose-dependently. Also it blocked the activities of inflammation-related signals such as nuclear factor-kappa B ($NF-{\kappa}B$) and inducible nitric oxide synthase (iNOS). For example, it had an inhibitory effect on the activation of $NF-{\kappa}B$ (p50) and iNOS proteins at 200 ${\mu}g/mL$ MIL glycoprotein. Here, we speculate that MIL glycoprotein is one of natural antioxidants and of modulators of the BPA-induced inflammation.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.40 no.4
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• pp.423-430
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• 2014

In this study, the antioxidative effects for the extracts of purple sweet potato (Ipomoea batatas L. Lam.) were investigated. The purple sweet potato was extracted with 70% ethanol and the ethyl acetate fraction was obtained from the extracts. The yields of extract and ethyl acetate fraction were 39.2% and 3.49% per dried powder, respectively. To confirm the antioxidative effects of the extracts, free radical scavenging activities (1,1-diphenyl-2-picrylhydrazyl), total antioxidant capacity by luminol-dependent chemiluminescence assay and the protective effects against reactive oxygen species (ROS) in erythrocytes were measured. Free radical scavenging activities ($FSC_{50}$) of the 70% ethanol extract and ethyl acetate fraction were $90.16{\mu}g/mL$ and $7.69{\mu}g/mL$, respectively. The free radical scavenging activity of ethyl acetate fraction was higher than that of (+)-${\alpha}$-tocopherol ($8.98{\mu}g/mL$). Total antioxidant capacities ($OSC_{50}$) of the 70% ethanol extract and ethyl acetate fraction were $5.75{\mu}g/mL$ and $1.92{\mu}g/mL$, respectively. The capacity of ethyl acetate fraction was similar to L-ascorbic acid, known as a prominent water soluble antioxidant ($1.50{\mu}g/mL$). The cellular protective effects of the ethyl acetate fractions on the $^1O_2$-induced cellular damage of human erythrocytes were increased in a concentration dependent manner ($5{\sim}50{\mu}g/mL$). The ${\tau}_{50}$ value in $5{\mu}g/mL$ was 45.6 min which was higher than that of (+)-${\alpha}$-tocopherol in all concentrations. These results indicate that the ethyl acetate fraction of purple sweet potato (I. batatas) has the excellent antioxidative capacity and could be applicable to anti-aging cosmeceutical ingredients for skin aging inhibition.

• Korean Journal of Environmental Biology
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• v.38 no.2
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• pp.271-277
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• 2020

Toxicities to many organs caused by humidifier disinfectants have been reported. Recently, humidifier disinfectants have been reported to cause cardiovascular, embryonic, and hepatic toxicities. This study was designed to investigate the toxic mechanism of humidifier disinfectants and compare toxicity in a cellular model and a zebrafish animal model. Because brain toxicity and skin toxicity have been less studied than other organs, we evaluated toxicity in a human dermal cell line and zebrafish under various concentrations of humidifier disinfectants that included polyhexamethyleneguanidine phosphate (PHMG), oligo-[2-(2-ethoxy)-ethoxyethyl-guanidinium-chloride] (PGH) and methylchloroisothiazolinone/methylisothiazolinone (CMIT/MIT). A human dermal fibroblast cell line was treated with disinfectants (0, 2, 4, 6, 8, and 16 mg L^-1) to compare their cytotoxicity. The fewest PHMG-treated cells survived (up to 33%), while 49% and 40% of the PGH- and CMIT/MIT-treated cells, respectively, survived. The quantification of oxidized species in the media revealed that the PHMG-treated cells had the highest MDA content of around 28 nM, while the PGH- and CMIT/MIT-treated cells had 13 and 21 nM MDA, respectively. As for brain toxicity, treatment of the zebrafish tank water with CMIT/MIT (final 40 mg L^-1) for 30 min resulted in a 17-fold higher production of reactive oxygen species (ROS) than in the control. Treatment with PGH or PHMG (final 40 mg L^-1) resulted in 15- and 11-fold higher production, respectively. The humidifier disinfectants (PHMG, PGH, and CMIT/MIT) showed severe dermal cell toxicity and brain toxicity. These toxicities may be relevant factors in understanding why some children have language disorders, motor delays, and developmental delays from exposure to humidifier disinfectants.

• Journal of Life Science
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• v.30 no.4
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• pp.370-378
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• 2020

This study aimed to investigate the hepatoprotective effect of Dendropanax morbifera (D. morbifera) leaf hot-water extract on carbon tetrachloride (CCl₄)-treated HepG2 cells. Treatment with D. morbifera leaf hot-water extract increased the cell viability of CCl₄-treated HepG2 cells without inducing cytotoxicity. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) released by CCl₄-treated cells were 27.6 U/L and 52.4 U/L, respectively, and were significantly higher than those in untreated control cells (10.0 U/L and 15.2 U/L, respectively). Moreover, the level of γ-glutamyl transpeptidase (GGT) was 5.4 times higher, while that of glutathione was 44.0% lower in CCl₄-treated cells than in control cells. However, treatment with D. morbifera leaf hot-water extract resulted in a dose-dependent decrease in the levels of ALT, AST, and GGT, and an increase in the level of glutathione. Moreover, the malondialdehyde (MDA) content in CCl₄-treated HepG2 cells was effectively reduced after treatment with D. morbifera leaf hot-water extract. Additionally, overproduction of intracellular lipids induced by CCl₄ treatment was effectively inhibited by D. morbifera leaf hot-water extract treatment. Furthermore, DCFDA staining showed that overproduction of reactive oxygen species (ROS) induced by CCl₄ treatment was effectively reduced by treatment with D. morbifera leaf hot-water extract. Our results indicate that owing to its beneficial effects, D. morbifera leaf extract has considerable potential as a functional food material for liver protection.

• Journal of Applied Biological Chemistry
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• v.54 no.3
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• pp.206-213
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• 2011

Hepatoprotective effects of Monascus pilosus mycelial ethanol extract (MPME) were examined in high-fat diet induced-obese rats. The rats were randomly divided into 2 groups; normal control (NC) and a high-fat and high cholesterol diet group (HFC). The HFC diet group was fed a 5L79 diet supplemented with 15% lard and 1% cholesterol for 3 weeks for induction of obesity. And then, the rats were divided into 4 groups (n=5); the NC, a HFC diet obesity control group (HF), 0.5% MPME supplemented HFC diet group (MPM), and 2% conjugated linoleic acid (CLA) supplemented HFC diet group for 7 weeks. Whereas the daily weight gain of NC and HFC groups were 3.48 g and 4.48 g, respectively, those of MPM and CLA were 3.09 g and 4.38 g, respectively. Furthermore, activity of serum alanine and aspartic aminotransferase in HF was markedly higher than those of NC group, but, the activity in MPM and CLA was significantly lower than HF. Hepatic reduced glutathione content in MPM and CLA was higher than HF. On the contrary, hepatic lipid peroxide content in MPM and CLA was significantly lower than HF. In conclusion, although the precise mechanisms of the hepatoprotective effects of the MPME in this study are unknown, our study provides experimental evidence that MPME may prevent obesity and hepatic damage by high-fat and high cholesterol diet via inhibition of lipid absorption and induction of reactive oxygen spices scavenging enzyme such as superoxide dismutase.

• Journal of Food Hygiene and Safety
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• v.34 no.4
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• pp.404-411
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• 2019

This study was carried out to investigate the antioxidant effects of extracts from 9 species of forest plants in Korea. DPPH, ABTS, $NaNO_2$, hydrogen peroxide radical scavenging activity and reducing power activity were evaluated to measure the antioxidant activities of plant extracts. As a result, Geranium thunbergii has been identified as the most effective antioxidant resource. Also, total phenolic content was highest in Geranium thunbergii ($303.94{\pm}0.63mg\;GAE/g$) among 9 species extracts. Total flavonoid content was highest in Rosa multiflora ($24.32{\pm}0.22mg\;QE/g$) and proanthocyanidin content was highest in Vitis ficifolia ($279.00{\pm}4.58mg\;CE/g$) among 9 species extracts. In addition, the protective effect of plant extracts in $H_2O_2-induced$ human dermal fibroblast (HDF) cell systems were also assessed. Significant protective effects in $H_2O_2-induced$ human dermal fibroblast (HDF) cell systems were found in all plant extracts, especially in Geranium thunbergii. These results suggest that Geranium thunbergii could be a potential natural resource for antioxidant activity.

• Korean Journal of Food Science and Technology
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• v.49 no.5
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• pp.524-531
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• 2017

The study aimed to investigate the antioxidant activity and neuroprotective effect of the ethyl acetate fraction from Orostachys japonicus A. Berger extract (EFOJ) and its main constituent compounds. Among all fractions, the highest content of total phenolics was found in EFOJ. The antioxidant activity of EFOJ was confirmed through the 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 1-1-diphenyl-2-picryl-hydrazyl (DPPH), ferric reducing antioxidant power (FRAP) assays and the inhibitory effect of malondialdehyde (MDA). In addition, we ascertained that EFOJ not only decreased the intracellular ROS level, but also protected the neuronal cells against $H_2O_2$-induced oxidative stress. In liquid chromatography-mass spectrometry analysis, the following were found to be the main compounds of EFOJ: quercetin-3-O-glucoside, kaempferol-3-O-rutinoside, kaempferol-3-O-glucoside, and kaempferol-3-O-rhamnoside. Consequently, these results suggested that the protective effect on neuronal cells was based on the antioxidant activities of the physiologically active compounds of Orostachys japonicus A. Berger extract, which could therefore help to mitigate neurodegenerative diseases.

• Journal of Life Science
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• v.19 no.5
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• pp.633-638
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• 2009

We investigated the inhibitory effects of solvent extracts from dried tuna on the growth of cancer cell lines (HT1080 human fibrosarcoma and HT-29 human colon cancer cells) and $H_2O_2$-induced oxidative stress. Inhibitory effects of acetone with methylene chloride (A+M) and methanol (MeOH) extracts on the growth of HT1080 and HT-29 cancer cells increased in a dose dependent manner (p<0.05). The inhibitory effect was more significant on the growth of HT1080 cells, and A+M extracts had a higher inhibitory effect compared to MeOH extracts. The treatments of hexane, 85% aq. methanol, butanol and water fractions significantly inhibited the growth of both cancer cells (p<0.05). Among the fractions, hexane and 85% aq. methanol fractions showed higher inhibitory effects. In order to determine the protective effect on $H_2O_2$-induced oxidative stress, a DCHF-DA (dichlorodihydrofluorescin diacetate) assay was conducted. All fractions, including crude extracts of dried tuna, appeared to significantly reduce the levels of intracellular reactive oxygen species (ROS) with dose responses (p<0.05). Among the fractions, BuOH and 85% methanol fractions showed a higher protective effect on the production of lipid peroxides. These results indicate that the consumption of tuna may be recommended as a potent functional food for preventing cellular oxidation and cancer.