• Journal of Acupuncture Research
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• 제20권4호
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• pp.1-10
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• 2003

Objective: The purpose of this study was to determine the effects of Puerariae radix(PR) herb-acupuncture on nitric oxide synthase(NOS) expression in hippocampus of alcohol-intoxicated Sprague-Dawley(SD) rats. Methods: SD rats were randomly assigned into 6 groups; normal group, control group, alcohol with herb-acupuncture group(0.3, 3, 30 and 300mg/kg PR). Normal groups were received with NaCl, while alcohol intoxication groups were injected intraperitoneally with alcohol(2g/kg) twice per day for 3 days. Herb-acupuncture groups were injected on Zhongwan(CV12) for 5 consecutive days. For the detection of NADPH-d-positive cells in hippocampus, immunohistochemistry was performed. Results: n control group, a significant decrease in NADPH-d-positive cells was observed compared to normal group. In alcohol with herb-acupuncture group, NADPH-d-positive cells increased significantly compared to control group. Conclusions: The present results revealed that NOS expression is enhanced in the hippocampus of SD rats through PR herb-acupuncture in an acute alcoholic intoxication condition.

• Tuberculosis and Respiratory Diseases
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• 제70권6호
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• pp.482-489
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• 2011

Background: Based on the assertion that apocynin diminishes acute lung injury (ALI) by inhibition of NADPH oxidase, the effect of apocynin was tested in interleukin-$1{\alpha}$ (IL-1)-induced ALI in rats. Methods: IL-1 was insufflated into the trachea of Sprague-Dawley rats to induce ALI, and apocynin (8 mg/kg) was given intravenously for inhibition of NADPH oxidase. In addition, we determined whether apocynin inhibited generation of superoxide anions from isolated human neutrophils. Five hours after IL-1 instillation, lung injury parameters, expression of cytosolic phospholipase A2 (cPLA2) by cells from bronchoalveolar lavage (BAL), an index of oxidative stress in lung tissues (${\gamma}$-glutamyltranspeptidase, activity), and ultrastructure of alveolar type II (AT II) cells were evaluated. Results: Apocynin decreased the generation of free radicals from phorbol myristate (PMA)-activated neutrophils in vitro, but did not ameliorate ALI. IL-1 induced enhancement of the expression of cPLA2 on neutrophils was not altered by apocynin. Conclusion: Apocynin induced suppression of the generation of superoxide anions from neutrophils by inhibition of NADPH oxidase does not attenuate IL-1-induced ALI in rats.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.5-7
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• 2003

NADPH is an essential co-factor for fat and cholesterol biosynthesis. However, the role of cytosolic NADP$\^$＋/-dependent isocitrate dehydrogenase (IDPc), a putative NADPH producer, in the control of the fat and cholesterol metabolism has not been assessed. Here we report that increased or decreased IDPc expression in 3T3-Ll fat cells promoted or retarded adipogenesis, respectively. Furthermore, overexpression of IDPc in transgenic mice exhibited fatty liver, hypertriglyceridemia, hypercholesterolemia and obesity by increasing NADPH production leading to subsequent stimulation of acetyl-coenzyme A and malonyl-coenzyme A consumption. In contrast, administrations of a synthetic IDPc inhibitor, DAl1004, to ob/ob mice effectively reduced body weight with lowering cholesterol and triglyceride levels. In addition, a positive relationship (${\gamma}$ = 0.69, $\rho$<0.0l) between plasma IDPc activity and body mass indexes was observed in 98 randomly-selected human volunteers. Our findings strongly indicate that NADPH produced by IDPc plays an important role in controlling body fat and lipid biosynthesis.

• Toxicological Research
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• 제13권3호
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• pp.251-256
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• 1997

Toluene inhalation increases glutamate level and its receptor in various brain regions. In this study, nitric oxide synthase (NOS) activities were investigated in various rat brain regions using NADPH diaphorase staining method which examined histochemical changes of NOS in the neural cells. Also, in vitro LDH leakage assay and MTT test were performed to investigate the toxic influences of toluene in cultured granule cell of rat cerebellum which was significantly affected with toluene in vivo. Rats were exposed to toluene of 10000 ppm for 3 days. 7 days and 14 days by 20 min $\times$ 2 times a day. NADPH diaphorase staining was processed in the different brain regions after inhalation. NADPH diaphorase staining density was not significantly changed at 3 days inhalation group, but the density decreased in proportion to the duration of toluene inhalation. Over 30% of staining density was decreased at 14 days group which was maximum duration of inhalation in this study. The tendency of staining density decrease was significant in granule cell of cerebellum. Cell death by toluene exposure was observed in cultured cerebellar granule cell. $EC_{50}$ measured with LDH leakage assay and MTT test were 43 mM and 72 mM respectively.

• 약학회지
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• 제25권4호
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• pp.145-151
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• 1981

The effect of ginseng methanol extract on hepatic drug metabolizing enzyme in rat was investigated. The ginseng methanol extract (100mg/kg) was administered orally to Sprague Dawley rats for 7days and the contents of cytochrome $P_{450}$ and NADPH cytochrome c reductase in liver were measured by the method of Stanton et al. and Mazel respectively. The content of liver cytochrome $P_{450}$ and NADPH cytochrome c reductase in the rats treated with ginseng methanol extract (100mg/kg) were increased by 21.9% and l6.6% respectively and their increases were statistically significant. Single i.p. injection of phenobarbital (100mg/kg) to the rats produced approximately 25% increase in cytochrome $P_{450}$ content in this investigation and further stimulation was produced in the rats pretreated with ginseng methanol extract (100mg/kg). On the other hand, single i.p. injection of 95% $CCl_{4}$ (0.5ml/kg) showed 29% decrease in cytochrome $P_{450}$ content and 10.5% decrease in NADPH cytochrome c reductase activity. The degree of inhibition of cytochrome $P_{450}$ content in the rats pretreated with ginseng methanol extract (100mg/kg) was similar to that observed in the $CCl_{4}$ alone treated group, but NADPH cytochrome c reductase activity was increased by 65% in the rats pretreated with ginseng methanol extract (100mg/kg). These results suggest that ginseng is the hepatic drug metabolizing enzyme inducing agent in the rat and the effect is similar to phenobarbital.

• Biomolecules & Therapeutics
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• 제28권1호
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• pp.25-33
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• 2020

Several recent studies have reported that reactive oxygen species (ROS), superoxide anion and hydrogen peroxide (H₂O₂), play important roles in various cellular signaling networks. NADPH oxidase (Nox) isozymes have been shown to mediate receptor-mediated ROS generation for physiological signaling processes involved in cell growth, differentiation, apoptosis, and fibrosis. Detectable intracellular levels of ROS can be induced by the electron leakage from mitochondrial respiratory chain as well as by activation of cytochrome p450, glucose oxidase and xanthine oxidase, leading to oxidative stress. The up-regulation and the hyper-activation of NADPH oxidases (Nox) also likely contribute to oxidative stress in pathophysiologic stages. Elevation of the renal ROS level through hyperglycemia-mediated Nox activation results in the oxidative stress which induces a damage to kidney tissues, causing to diabetic nephropathy (DN). Nox inhibitors are currently being developed as the therapeutics of DN. In this review, we summarize Nox-mediated ROS generation and development of Nox inhibitors for therapeutics of DN treatment.

• Journal of Microbiology and Biotechnology
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• 제33권10호
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• pp.1361-1369
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• 2023

Corynebacterium glutamicum (C. glutamicum) has been considered a very important and meaningful industrial microorganism for the production of amino acids worldwide. To produce amino acids, cells require nicotinamide adenine dinucleotide phosphate (NADPH), which is a biological reducing agent. The pentose phosphate pathway (PPP) can supply NADPH in cells via the 6-phosphogluconate dehydrogenase (6PGD) enzyme, which is an oxidoreductase that converts 6-phosphogluconate (6PG) to ribulose 5-phosphate (Ru5P), to produce NADPH. In this study, we identified the crystal structure of 6PGD_apo and 6PGD_NADP from C. glutamicum ATCC 13032 (Cg6PGD) and reported our biological research based on this structure. We identified the substrate binding site and co-factor binding site of Cg6PGD, which are crucial for understanding this enzyme. Based on the findings of our research, Cg6PGD is expected to be used as a NADPH resource in the food industry and as a drug target in the pharmaceutical industry.

• Molecules and Cells
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• 제27권5호
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• pp.557-562
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• 2009

We examined the effects of the NADPH oxidase p22phox C242T polymorphism on endurance exercise performance and oxidative DNA damage in response to acute and chronic exercises. One hundred three subjects were recruited, among which 26 healthy subjects (CC: 12, TC: 12, and TT: 2) were studied during rest, exercise at 85% $VO_2max$, and recovery before and after 8 weeks of treadmill running. Lymphocyte DNA damage increased significantly in response to exercise (p < 0.05). There were no significant differences in plasma MDA, SOD concentrations and lymphocyte DNA damage between CC genotype and T allele group, but significant endurance training differences were observed. Endurance training increased exercise time to exhaustion in both the CC genotype and T allele groups (p < 0.05) but no significant difference was found between groups. The results of the current study with young, healthy, Korean men are interpreted to mean that 1) the majority had the CC genotype of the NADPH oxidase p22phox C242T polymorphism (82.5%: CC, 15.5%: TC, 1.9%: TT), 2) acute exercise increased lymphocyte DNA damage, 3) endurance training significantly increased exercise time to exhaustion, and alleviated lymphocyte DNA damage, and 4) The NADPH oxidase p22phox C242T polymorphism, however, did not alter lymphocyte DNA damage or exercise performance at rest, immediately after exercise, or during recovery.

• 대한약침학회지
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• 제6권2호
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• pp.57-65
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• 2003

Objective : This study was carried out to systemically investigate the effect of Joongwan(中脘; CV12) acupuncture in cerebrum and cerebellum of indomethacin-induced gastrointestinal disease in SD-rats. Method : 1. We induced gastrointestinal disease by indomethacin oral administration in SD-rats. 2. We selected Joongwan(中脘; CV12) acupuncture point that generally have been used to treat gastrointestinal disease. 3. We categorized SD-rats into three groups as followings. (1) Normal group : The group without any management (2) Control group : The group with indomethacin-induced gastrointestinal disease (3) Treated group : The group that Joongwan(中脘; CV12) acupuncture was performed after inducing gastrointestinal disease 4. We figured out the effect of acupuncture by analyzing staining degree of NADPH-diaphorase in cerebrum and cerebellum. Results : 1. Cerebrum (1) Normal group : The degree of staining was very low. (2) Control group : NADPH-diaphorase was mainly stained in cerebral cortex and the stained region was wider than Normal group. (3) Treated group : The degree and region of staining was higher and wider than the other goups. Sometimes the intensively stained regions were observed. 2. Cerebellum In both cases of Control group and Treated group, the regions in cortex were stained mainly. But, between Control group and Treated group, there was no remarkable difference. Conclusion : In case of cerebellum, there was no remarkable result. On the other hand, in case of cerebrum, there were certain differences among three groups. Through those results, we could conclude that Joongwan(中脘; CV12) acupuncture treatment was able to affect NADPH-diaphorase expression in the cerebrum of SD-rats that have gastrointestinal disease with indomethacin-inducing.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.191-200
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• 2018

Chalcone, (2E)-1,3-Diphenylprop-2-en-1-one, and its synthetic derivatives are known to possess anti-oxidative and anti-inflammatory properties. In the present study, we prepared a novel synthetic chalcone compound, (E)-1-(4-hydroxyphenyl)-3-(2-(trifluoromethoxy)phenyl)prop-2-en-1-one name (YJI-7), and investigated its inhibitory effects on endotoxin-stimulated production of reactive oxygen species (ROS) and expression of inflammatory mediators in macrophages. We demonstrated that treatment of RAW 264.7 macrophages with YJI-7 significantly suppressed lipopolysaccharide (LPS)-stimulated ROS production. We also found that YJI-7 substantially decreased NADPH oxidase activity stimulated by LPS, indicating that YJI-7 regulates ROS production via modulation of NADPH oxidase in macrophages. Furthermore, YJI-7 strongly inhibited the expression of a number of inflammatory mediators in a gene-selective manner, suggesting that YJI-7 possesses potent anti-inflammatory properties, as well as anti-oxidative activity. In continuing experiments to investigate the mechanisms that could underlie such biological effects, we revealed that YJI-7 suppressed phosphorylation of p38MAPK and JNK stimulated by LPS, whereas no significant effect on ERK was observed. Furthermore, LPS-stimulated production of ROS, activation of NADPH oxidase and expression of inflammatory mediators were markedly suppressed by treatment with selective inhibitor of p38MAPK (SB203580) and JNK (SP600125). Taken together, these results demonstrated that YJI-7, a novel synthetic chalcone derivative, suppressed LPS-stimulated ROS production via modulation of NADPH oxidase and diminished expression of inflammatory mediators, at least in part, via down-regulation of p38MAPK and JNK signaling in macrophages.