• Biomedical Science Letters
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• v.20 no.2
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• pp.56-61
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• 2014

This study attempted to confirm the antioxidative potential of luteolin against tert-butyl hydroperoxide (t-BHP) induced oxidative damage and to investigate its molecular mechanism related to glutathione (GSH)-dependent enzymes in HepG2 cells. Treatment with luteolin resulted in attenuation of t-BHP induced generation of reactive oxygen species (ROS) and oxidative stress-mediated cell death. In addition, accelerated expression of GSH-dependent antioxidative enzymes, glutathione peroxidase (GPx) and glutathione reductase (GR), and heme oxygenase (HO)-1, as well as strengthened GSH content was induced by treatment with luteolin, which was in accordance with increased nuclear translocation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), a transcription factor for phase 2 enzymes, in a dose-dependent manner. These results suggest that the cytoprotective potential of luteolin against oxidative damage can be attributed to fortified GSH-mediated antioxidative pathway and HO-1 expression through regulation of Nrf2 in HepG2 cells.

• Environmental Analysis Health and Toxicology
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• v.21 no.2 s.53
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• pp.103-113
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• 2006

This study examined effects of crude oil on the phase II drug-metabolizing enzymes UDP-glucuronosyl transferase (UDPGT) and glutathione S-transferase (GST) in mussel Mytilus edulis and rockfish Sebastes schlegeli, a representative bivalve and a culture fish, respectively. This work also intended indirectly to evaluate the post impact recovery from the massive oil tanker spillage accidents occurred during the summer of 1995 in the sea area off Yosu City, Chonnam. For these, enzyme activities of UDPGT and GST were examined in the fish and mussel following laboratory exposure to fresh crude oil, weathered oil, field-obtained oil residues, or in the field biota samples. Decreased GST activity was observed in rock fish following exposure to oil-soluble fraction (OSF) of fresh oil. A similar diminished GST activity was also observed after OSF of artificially weathered oil. OSF of field oil residues retrieved from the spillage area approximately 1 year later also exerted a slight inhibition of GST to rockfish. There was neither a change in UDPGT in rockfish, nor were there changes in mussel in both enzymes to any oil fractions. We could not observe any difference in the two enzymes either in rockfish or mussel sampled from the field during $1.5{\sim}2.0$ years post spillage, indicating that their enzyme systems might had been recovered by the sampling time. In conclusion, it seems that the inhibition of GST activity in rockfish is a biomarker response to crude oil exposure. The results, however, must be interpreted with care, as the inhibition nay reflect various factors such as oil concentration, duration and water temperature.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.83-84
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• 2001

Results from laboratory experiments indicate that induction of phase II enzymes by dietary constituents leads to inactivation of genotoxins. In animal studies glutathione S-transferase (GST) induction was paralleled by a reduction of chemically induced tumours. However data on induction of phase II enzymes in humans is scarce. Therefore we carried out intervention studies in which we investigated the effect of cruciferous vegetables on GST induction, and studied the effects of these vegetables on meat derived urinary mutagenicity.(omitted)

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.386.2-386.2
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• 2002

We investigated the effect of tectorigenin (1) with hypoglycemic and hypolipidemic effects on Phase I and II enzymes and TF activity to elucidate the action of an immunosuppressive compound (1) in the diabetic rat. Compound 1 was obtained from the hydrolysis of tectoridin easily isolated from the flower of Pueraria thunbergiana(Leguminosae). Puerariae Flos has been used as therapeutics for diabetes mellitus in traditional medicine of Korea. (omitted)

• Proceedings of the Korean Society of Life Science Conference
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• 2001.02a
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• pp.38-38
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• 2001

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.05a
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• pp.96-106
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• 2001

The phase II detoxifying enzymes are inducible by a variety of compounds and play an essential role for the protection of cells. Many of chemoprotective agents trigger cellular signals for the phase II enzyme induction, which subsequently activate gene transcription through ARE activation.(omitted)

• Journal of Life Science
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• v.27 no.3
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• pp.310-317
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• 2017

Mammalian cells control cellular homeostasis using a variety of defensive enzymes in order to combat against environmental oxidants and electrophiles. NF-E2-related factor-2 (NRF2) is a transcription factor that, in response to an exposure to oxidative stress, translocates into the nucleus and modulates the inducible expression of various phase II cytoprotective enzymes by binding to the antioxidant response element (ARE). In the present study, we have acquired 400 ethanol extracts of traditional medicinal plants and attempted to find out possible extract(s) that can increase the NRF2/ARE-dependent gene expression in human keratinocytes. As a result, we have identified that ethanol extracts of Rheum undulatum and Inula japonica strongly activated the ARE-dependent luciferase activity in HaCaT- ARE-luciferase cells. Exposure of ethanol extracts of Rheum undulatum and Inula japonica increased the viability and activated transcription and translation of NRF2-dependent phase II cytoprotective enzymes in HaCaT cells, such as heme oxygenase-1 (HO-1) and NAD[P]H:quinone oxidorecutase-1 (NQO1). In addition, ethanol extracts of Rheum undulatum and Inula japonica suppressed 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced generation of intracellular reactive oxygen species (ROS), thereby inhibiting the formation of 8-hydroxyguanosine (8-OHG) and 4-hydroxynonenal (4-HNE) in HaCaT cells. Together, our results demonstrate that ethanol extracts of Rheum undulatum and Inula japonica exert anti-oxidant effects via the induction of NRF2/ARE-dependent gene expression in human keratinocytes.

• Journal of Society of Preventive Korean Medicine
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• v.12 no.1
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• pp.73-87
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• 2008

In recent years, there has been a globally increasing application of herbal medicines and dietary supplements to treat various chronic diseases and to promote health. However, there are increasing clinical reports on the organ toxicities associated with consumption of herbal medicines. In general, most xenobiotics are metabolized by Phase I reaction(the main enzyme : cytochrome P450) and Phase II reaction. However, reactive oxygen species, free radicals and electrophils are produced inevitably during xenobiotics metabolism. These toxic species and metabolites are increased whenever the endogenous substances and enzymes for Phase II reaction not available. In addition, herbal-drug interactions are pharmacokinetic, with most actually or theoretically affecting the metabolism of the affected product by way of the cytochrome P450 enzymes. This review updated the knowledge on metabolic activation of herbal components and its clinical and toxicological implications. Also, the possible way for preventing the side-effects by herbal-medicine use was suggested.

• Biomolecules & Therapeutics
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• v.20 no.2
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• pp.144-151
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• 2012

The molecular mechanisms by which a variety of naturally-occurring dietary compounds exert chemopreventive effects have been a subject of intense scientific investigations. Induction of phase II detoxification and anti-oxidant enzymes through activation of Nrf2/ARE-dependent gene is recognized as one of the major cellular defense mechanisms against oxidative or xenobiotic stresses and currently represents a critical chemopreventive mechanism of action. In the present review, the functional significance of Keap1/Nrf2 protein module in regulating ARE-dependent phase II detoxification and anti-oxidant gene expression is discussed. The biochemical mechanisms underlying the phosphorylation and expression of Keap1/Nrf2 proteins that are controlled by the intracellular signaling kinases and ubiquitin-mediated E3 ligase system as well as control of nucleocytoplasmic translocation of Nrf2 by its innate nuclear export signal (NES) are described.

• Natural Product Sciences
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• v.9 no.4
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• pp.235-240
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• 2003

Tectorigenin has an apoptosis-inducing ability and immunosuppressive activity. We investigated the effect of tectorigenin on Phase I and II enzyme activities to elucidate the pharmacological action of the immunosuppressive tectorigenin in the diabetic rat. This compound was obtained from the hydrolysis of tetoridin isolated from the flower of Pueraria thumbergiana (Leguminosae). This crude drug (Puerariae Flos) has been used as a therapeutic for diabetes mellitus in traditional Korean medicine. Tecotrigenin inhibited the formation of malondialdehyde (MDA) and hydroxy radicals in serum and liver but promoted superoxide dismutase (SOD) activity. Low MDA contents and low xanthine oxidase and aldehyde oxidase activities were observed in the tectorigenin-treated rats, suggesting that such Phase I enzyme activities are the major source of lipid peroxidation. However, tectorigenin increased Phase II enzyme activities such as SOD, glutathione peroxidase and catalase, suggesting the activation of free radical-scavenging enzymes. The activities of tectorigenin were comparable to those of glibenclamide, which was employed as a positive control. These results suggest that tectorigenin may share some biological properties with glibenclamide in insulin-dependent-diabetes mellitus (IDDM).