• Title/Summary/Keyword: ROS level

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Protective Effect of Dendropanax morbifera Leaf Extract on CCl4-induced Oxidative Damage in HepG2 Cells (사염화탄소로 유발된 산화적 손상에 대한 황칠나무 잎 추출물의 간세포 보호 효과)

  • Park, Se-Ho;Lee, Jae-Yeul;Jhee, Kwang-Hwan;Yang, Seun-Ah
    • 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.

Induction of Phase I, II and III Drug Metabolism/Transport by Xenobiotics

  • Xu Chang Jiang;Li Christina YongTao;Kong AhNg Tony
    • 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.

Neuronal Cell Protective Effect of New Green Extract against H2O2-induced Oxidative Stress and Analysis of Bioactive Compounds (과산화수소(H2O2)로 유도된 산화 스트레스에 대한 뉴그린 추출물의 신경세포 보호효과 및 생리활성물질 분석)

  • Ha, Jeong Su;Park, Seon Kyeong;Park, Chang Hyeon;Seung, Tae Wan;Guo, Tian Jiao;Kang, Jin Young;Lee, Du Sang;Kim, Jong Min;Lee, Uk;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.47 no.5
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    • pp.673-679
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    • 2015
  • In vitro antioxidant activities and neuronal cell protective effects of the ethyl acetate fraction of a new green extract (Brassica oleracea var. botytis aut italiana) against $H_2O_2$-induced oxidative stress were investigated, and its industrial feasibility was evaluated. The extract showed the highest contents of total phenolic compounds among other extracts as well as a 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging activity and malondialdehyde (MDA) inhibitory effect. This extract not only decreased the intracellular reactive oxygen (ROS) level but also protected the neuronal cells against $H_2O_2$-induced oxidative stress. On analysis using gas chromatograph-mass spectrometry, the following phenolic compounds were identified: quinic acid, ferulic acid, and caffeic acid. Collectively, these results suggest that this new green extract could contain functional substances that would help prevent the risk of neurodegenerative disease.

Protective effects of Aruncus dioicus var. kamtschaticus extract against hyperglycemic-induced neurotoxicity (포도당 처리로 유도된 뇌신경세포 독성에 대한 눈개승마 추출물의 보호효과)

  • Park, Su Bin;Lee, Uk;Kang, Jin Yong;Kim, Jong Min;Park, Seon Kyeong;Park, Sang Hyun;Choi, Sung-Gil;Heo, Ho Jin
    • Korean Journal of Food Science and Technology
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    • v.49 no.6
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    • pp.668-675
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    • 2017
  • To assess the physiological effects of Aruncus dioicus var. kamtschaticus extract on cytoxicity of a neuronal cell line, antioxidant activity, and neuroprotection against intensive glucose-induced oxidative stress were quantitated. Compared to the other fractions, the ethyl acetate fraction of Aruncus dioicus var. kamtschaticus (EFAD) showed the highest total phenolics and flavonoids. The 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) assay and malondialdehyde inhibitory effect test confirmed the superior antioxidant activity of EFAD. Moreover, EFAD also decreased the intracellular ROS level and suppressed neuronal cell death against intensive glucose- or $H_2O_2$-induced oxidative stress. Additionally, assessment of ${\alpha}$-glucosidase and acetylcholinesterase inhibitory activities revealed that EFAD was an effective inhibitor of ${\alpha}$-glucosidase and acetylcholinesterase. Finally, high-performance liquid chromatography analysis identified caffeic acid as the main ingredient of EFAD. Overall, these results suggest that the EFAD is a good natural source of biological compounds that counteract hyperglycemic neuronal defects.

Antioxidant, Antiaging and Antimicrobial Effects of Ethanolic Extract and Ethyl Acetate Fraction from Eclipta prostrata (한련초 에탄올 추출물과 에틸아세테이트 분획물의 항산화, 항노화 및 항균 효과)

  • Lee, Sang Lae;Song, Ba Reum;Shin, Hyuk Soo;Lee, Yun Ju;Park, Soo Nam
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.44 no.3
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    • pp.349-362
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    • 2018
  • An annual plant, Eclipta prostrata (Linn) is a member of the Asteraceae plant family and inhabited in tropical or subtropical regions of the world. Through many previous researches, E. prostrata has been extensively studied for its hepatoprotective effect, antivenom potential against viper venom, antioxidant, hair-growth, wound-healing efficacy and so on. In this study, for better understanding of the potential of E. prostrata as skin protectant, we conducted the experiments evaluating the antioxidant and antiaging efficacy. To this end, 50% ethanolic extract of E. prostrata and its ethyl acetate fraction were prepared and investigated. For the evaluation of antioxidant capacity of the samples, $FSC_{50}$ and $OSC_{50}$ were estimated. As a result, $OSC_{50}$ of ethyl acetate fraction was 2.7 times superior to $OSC_{50}$ of L-ascorbic acid, a well known antioxidant agent. Futhermore E. prostrata showed notable reactive oxygen species (ROS) scavenging effect and protective effect against $H_2O_2$ in the celluar level as well. Especially, in the $^1O_2$ induced hemolysis test, $64{\mu}g/mL$ of ethyl acetate fraction showed greater than 6 times increased retardation effect compare to control which means E. prostrata has remarkable antioxidant capacity. To validate the antiaging effect of the samples, we conducted elastase inhibition assay using elastase solution extracted from human skin fibroblasts, Hs68. As a result, $16{\mu}g/mL$ of each sample showed 6.8% and 14.0% of elastase inhibition respectively. Finally, antimicrobial activity of E. prostrata was assessed to validate the possibility as alternative preservative. From the result, ethyl acetate fraction showed oustanding antimicrobial activity as of methyl paraben, a well known chemical preservative. In conclusion, these results suggest that E. prostrata can be used as natural skin protectant or preservative as natural ingredient in food or cosmetics industry.

Alcohol Fermentation at High Temperature and the Strain-specific Characteristics Required to Endow the Thermotolerance of Sacchromyces cerevisiae KNU5377

  • Paik, Sang-Kyoo;Park, In-Su;Kim, Il-Sup;Kang, Kyung-Hee;Yu, Choon-Bal;Rhee, In-Koo;Jin, In-Gnyol
    • Proceedings of the Korean Society for Applied Microbiology Conference
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    • 2005.06a
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    • pp.154-164
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    • 2005
  • Saccharomyces cerevisiae KNU5377 is a thermotolerant strain, which can ferment ethanol from wasted papers and starch at 40$^{\circ}C$ with the almost same rate as at 30$^{\circ}C$. This strain showed alcohol fermentation ability to convert wasted papers 200 g (w/v) to ethanol 8.4% (v/v) at 40$^{\circ}C$, meaning that 8.4% ethanol is acceptable enough to ferment in the industrial economy. As well, all kinds of starch that are using in the industry were converted into ethanol at 40$^{\circ}C$ with the almost same rate as at 30$^{\circ}C$. Hyperthermic cell killing kinetics and differential scanning calorimetry (DSC) revealed that exponentially growing cells of this yeast strain KNU5377 were more thermotolerant than those of S. cerevisiae ATCC24858 used as a control. This intrinsic thermotolernace did not result from the stability of entire cellular components but possibly from that of a particular target. Heat shock induced similar results in whole cell DSC profiles of both strains and the accumulation of trehalose in the cells of both strains, but the trehalose contents in the strain KNU5377 were 2.6 fold higher than that in the control strain. On the contrary to the trehalose level, the neutral trehalase activity in the KNU5377 cells was not changed after the heat shock. This result made a conclusion that though the trehalose may stabilize cellular components, the surplus of trehalose in KNU5377 strain was not essential for stabilization of whole cellular components. A constitutively thermotolerant yeast, S. cerevisiae KNU5377, was compared with a relatively thermosensitive control, S. cerevisiae ATCC24858, by assaying the fluidity and proton ATPase on the plasma membrane. Anisotropic values (r) of both strains were slightly increased by elevating the incubation temperatures from 25$^{\circ}C$ to 37$^{\circ}C$ when they were aerobically cultured for 12 hours in the YPD media, implying the membrane fluidity was decreased. While the temperature was elevated up to 40$^{\circ}C$, the fluidity was not changed in the KNU5377 cell, but rather increased in the control. This result implies that the plasma membrane of the KNU5377 cell can be characterized into the more stabilized state than control. Besides, heat shock decreased the fluidity in the control strain, but not in the KNU5377 strain. This means also there's a stabilization of the plasma membrane in the KNU5377 cell. Furthermore, the proton ATPase assay indicated the KNU5377 cell kept a relatively more stabilized glucose metabolism at high temperature than the control cell. Therefore, the results were concluded that the stabilization of plasma membrane and growth at high temperature for the KNU5377 cell. Genome wide transcription analysis showed that the heat shock responses were very complex and combinatory in the KNU5377 cell. Induced by the heat shock, a number of genes were related with the ubiquitin mediated proteolysis, metallothionein (prevent ROS production from copper), hsp27 (88-fold induced remarkably, preventing the protein aggregation and denaturation), oxidative stress response (to remove the hydrogen peroxide), and etc.

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Protective effect on neuronal cells of Orostachys japonicus A. Berger extract against reactive oxygen species-induced neuronal cytotoxicity and active compounds (활성 산소종으로 야기된 산화스트레스에 대한 와송 추출물의 신경세포 보호효과 및 주요 생리활성물질)

  • Park, Su Bin;Lee, Du Sang;Kang, Jin Yong;Kim, Jong Min;Park, Seon Kyeong;Kang, Jeong Eun;Kwon, Bong Seok;Park, Sang Hyun;Lee, Chang Jun;Lee, Uk;Heo, Ho Jin
    • 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.

Effects of Supplemental Feather Digests on the Growth of Broiler Chicks and Taurine Content in the Broiler Meat (우모 가수분해물 첨가가 육계의 증체 및 계육 내 타우린 함량에 미치는 영향)

  • 홍성진;남궁환;김우연;백인기
    • Korean Journal of Poultry Science
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    • v.29 no.2
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    • pp.141-148
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    • 2002
  • Two experiments were conducted to investigate the effects of supplemental feather digests on the growth of broiler chicks and taurine content in the broiler meat. In experiment 1, a total of 40 broiler chickens(Ros $s_{R}$) were assigned to four dietary treatments: control(T1), regular feather meal(FM) diet(R-FM,T2), NaOH treated FM diet(NaOH-FM,T3), HNO) treated FM diet($HNO_{3}$ -FM, T4). In experiment 2, a total of 70 broiler chickens were assigned to seven dietary treatments: T1 to t4(same as those of Exp. 1), modified $HNO_{3}$ treated FM diet(M- $HNO_{3}$-FM, T5), hair meal diet(HM, T6) and 0.22% cystine supplemented diet(CYS, T7). Feather meals and hair meal were supplemented at the level of 5% in the diet. In experiment 1 and 2, weight gain of chicks frd with R-FM or NaOH-FM tended to be higher than control or $HNO_{3}$ -FM. In experiment 2, weight gain of chicks frd with CYS was the highest followed by R-FM, M-HN $O_3$-FM, NaOH-FM, control, HM and $HNO_{3}$ -FM. In experiment 1, taurine content in breast muscle of chicks fed NaOH-FM was sogmofocamtly higher(P<0.05) than control. In experiment 2, taurine content in breast muscle of chicks fed NaOH-FM and CYS tended to be higher than other groups. Taurine content in leg muscle was significantly different among treatments as NaOH-FM and R-FM being highest followed by M- $HNO_{3}$-FM, CYS, control, $HNO_{3}$ -FM and HM. Taurine content in the liver(Exp. 1 and 2) and heart(Exp. 2) were not significantly affected by the supplemental feather digests. These results indicated that 5% NaOH-FM in the diet was effective in increasing taurine content in breast and leg muscle of broiler chicks.s.

Antioxidative Effects of Tenebrio molitor Larvae Extract Against Oxidative Stress in ARPE-19 Cells (ARPE-19 세포에서 산화적 스트레스에 대한 갈색거저리 추출물의 항산화 효과)

  • Bong Sun, Kim;Ra-Yeong, Choi;Eu-Jin, Ban;Joon Ha, Lee;In-Woo, Kim;Minchul, Seo
    • Journal of Life Science
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    • v.32 no.11
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    • pp.865-871
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    • 2022
  • Tenebrio molitor larvae is well known as edible insect. Then, although it has been widely studied that Tenebrio molitor larvae has various bioactive functions such as antioxidant, anti-wrinkle, and anticancer. Nevertheless, antioxidant effects of Tenebrio molitor larvae water extract (TMH) has not been well described in Adult Retina Pigment Epithelial cell line (ARPE-19). In this study, we demonstrated that antioxidant effects of TMH against H2O2-induced oxidative stress in ARPE-19. Thus, we selected for our studies and performed a series of dose-response assay to determine the working concentration that lead to a consistent and high degree of cytotoxicity, which we defined as the level of H2O2 that killed 40% of the ARPE-19 cells. ARPE-19 cells were pre-treated with various concentrations of TMH (0.1 up to 2 mg/ml) before exposure to 300 µM H2O2. As we expected, TMH effectively prevented ARPE-19 cells from 300 µM H2O2-induced cell death in a dose-dependent manner. Furthermore, TMH inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) such as extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. Overall, the inhibitory effects of TMH on H2O2-induced apoptosis and oxidative stress were associated with the protection cleaved caspase-3, Bax, Bcl-2, and HO-1. The TMH suppressed H2O2-induced cell membrane leakage and oxidative stress in ARPE-19 cells. Thus, these results suggest that the TMH plays an important role in antioxidant effect in ARPE-19.