• Natural Product Sciences
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• v.24 no.1
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• pp.59-65
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• 2018

An isoform of NADPH oxidase (NOX), NOX2 is a superoxide-generating enzyme involved in diverse pathophysiological events. Although its potential as a therapeutic target has been validated, there is no clinically available inhibitor. Herein, NOX2-inhibitory activity was screened with the constituents isolated from Schisandra chinensis, which has been reported to have antioxidant and reactive oxygen species (ROS)-scavenging effects. Among the partitions prepared from crude methanolic extract, a chloroform-soluble partition showed the highest NOX2-inhibitory activity in PLB-985 cell-based NOX2 assay. A total of twenty nine compounds (1 - 29) were identified from the chloroform fraction, including two first isolated compounds; dimethyl-malate (25) and 2-(2-hydroxyacetyl) furan (27) from this plants. Of these constituents, two compounds (gomisin T, and pregomisin) exhibited an NOX2-inhibitory effect with the $IC_{50}$ of $9.4{\pm}3.6$, and $62.9{\pm}11.3{\mu}M$, respectively. They are confirmed not to be nonspecific superoxide scavengers in a counter assay using a xanthine-xanthine oxidase system. These findings suggest the potential application of gomisin T (6) and other constituents of S. chinensis to inhibit NOX2.

• Biomedical Science Letters
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• v.22 no.3
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• pp.107-114
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• 2016

Maintenance of fasting blood glucose levels is important for glucose homeostasis. Disruption of feedback mechanisms are a major reason for elevations of glucose level in blood, which is a risk factor for type 2 diabetes mellitus that is mainly caused by malfunction of pancreatic beta-cell and insulin. The fasting blood glucose level has been known to be influenced by genetic and environmental factors. Mitochondria have many functions for cell survival and death: glucose metabolism, fatty acid oxidation, ATP generation, reactive oxygen species (ROS) metabolism, calcium handling, and apoptosis regulation. In addition to these functions, mitochondria change their morphology dynamically in response to multiple signals resulting in fusion and fission. In this study, we aimed to examine association between fasting blood glucose levels and variants of the genes that are reported to have functions in mitochondrial dynamics, fusion and fission, using a cohort study. A total 416 SNPs from 36 mitochondrial dynamics genes were selected to analyze the quantitative association with fasting glucose level. Among the 416 SNPs, 4 SNPs of PRKACB, 13 SNPs of PPP3CA, 6 SNPs of PARK2, and 3 SNPs of GDAP1 were significantly associated. In this study, we were able to confirm an association of mitochondrial dynamics genes with glucose levels. To our knowledge our study is the first to identify specific SNPs related to fasting blood glucose level.

• Toxicological Research
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• v.33 no.4
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• pp.315-323
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• 2017

Preconceptual sex selection is still a highly debatable process whereby X- and Y-chromosome-bearing spermatozoa are isolated prior to fertilization of the oocyte. Although various separation techniques are available, none can guarantee 100% accuracy. The aim of this study was to separate X- and Y-chromosome-bearing spermatozoa using methods based on the viability difference between the X- and Y-chromosome-bearing spermatozoa. A total of 18 experimental semen samples were used, written consent was obtained from all donors and results were analysed in a blinded fashion. Spermatozoa were exposed to different pH values (5.5, 6.5, 7.5, 8.5, and 9.5), increased temperatures ($37^{\circ}C$, $41^{\circ}C$, and $45^{\circ}C$) and ROS level ($50{\mu}M$, $750{\mu}M$, and $1,000{\mu}M$). The live and dead cell separation was done through a modified swim-up technique. Changes in the sex-chromosome ratio of samples were established by double-label fluorescent in situ hybridization (FISH) before and after processing. The results indicated successful enrichment of X-chromosome-bearing spermatozoa upon incubation in acidic media, increased temperatures, and elevated $H_2O_2$. This study demonstrated the potential role for exploring the physiological differences between X-and Y-chromosome-bearing spermatozoa in the development of preconceptual gender selection.

• BMB Reports
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• v.32 no.6
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• pp.585-593
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• 1999

The water and methanol extracts of Artemisia argyi showed significant cytotoxicities against J774A.1 cells but not so much against normal leukocytes. The cytotoxicities were found to be dependent on the extract concentration and the incubation time. The concentration of water and methanol extracts inhibiting 50% of cell proliferation ($IC_{50}$) were estimated to be 44.2 mg/ml and 71.6 mg/ml, respectively. In the presence of Artemisia argyi water extract, total superoxide dismutase (CuZnSOD and MnSOD) activities of media, cytoplasmic and mitochondrial fractions of J774A.1 cells increased in accordance with cytotoxicity. MnSOD was found to be the main component of enhanced total SOD activities, particulary in the mitochondrial fraction. In contrast to SOD, catalase and glutathione peroxidase (GPx) were not found in any instance of the current investigation. In addition, substantial amount of $O_2^-$ appeared to be generated in the mitochondrial fraction under the influence of Artemisia argyi. All data put together, it is postulated that Artemisia argyi extracts seem to stimulate $O_2^-$ generation in mitochondria of J774A.1 cells with concomitant increases of SODs. Since $H_2O_2$, the reaction product of SOD on $O_2^-$, is known to be readily converted to very toxic $OH{\cdot}$ in the absence of catalase and/or GPx cooperation, toxicity derived from ROS such as $O_2^-$, $H_2O_2$, and $OH{\cdot}$ may be the main cause of necrosis and/or apoptosis of J774A.1 cells.

• Environmental Analysis Health and Toxicology
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• v.21 no.2 s.53
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• pp.127-138
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• 2006

In urban areas, diesel exhaust particles (DEP) are probably a major component of particulate matters, especially in Korea where drive many diesel vehicles. The aim of this study was to investigate genotoxic effects of DEP using single ceil gel electrophoresis. In order to evaluate the mechanisms of DEP genotoxicity, the rat microsome mediated and DNA repair enzyme treated comet assays together with conventional comet assay were performed. Total diesel particles (DEPT) was collected without site fractionation from diesel engine bus and dichloromethane extract was obtained. The organic extract of DEPT revealed DNA damage itself in NIH/3T3 cells. The level of DNA breaks plus oxidative DNA lesions and microsome mediated DNA damage was assessed by modified single cell gel eletrophoresis. DEPT was able to induce oxidative DNA damage as well as microsome mediated DNA damage. Vitamin C as an model antioxidant reduced DNA damage in endonuclase III treated comet assay. One of flavonoid, galangin as a CYP1A1 inhibitor. reduced DNA damage in the presence of S-9 mixture. $DEP_T$ is the sources of oxidative stress, but antioxidants can significantly reduce oxidative DNA dmage. And $DEP_T$ may contain indirect mutagens which can be inhibited by CYP1A1 inhibitors. The ethanol extracts of the mixed vegetables (BV) or the mixed fruits (BF) were evaluated for their in vitro antigenotoxic effects. BV and BF showed potent Inhibitory effects against DEPT induced DNA damage with oxidative DNA lesions and in the prescence of S-9 mixture. These results indicate that BV and BF could prevent cellular DNA damage by inhibiting oxidative stress and suppressing cytochrome P4501A1 in cell culture.

• The Journal of Internal Korean Medicine
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• v.37 no.3
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• pp.467-483
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• 2016

Objective: This study was performed to investigate the effect of IUS (Inulsan, an extract of Artemisiae capillaris (茵蔯), Curcumae longae (鬱金), and Crataegi fructus (山査)) on anti-hyperlipidemia, anti-oxidation, and anti-inflammation.Method: We administered water extracts of Artemisiae capillaris, Curcumae longae, and Crataegi fructus for three weeks to db/db mice (C57BL/Ks), animal models induced with type 2 diabetes mellitus. Mice were divided into three groups: normal (C57BL/6J mice group), control group (db/db mice without administration of IUS) and IUS group (db/db mice treated with IUS). Then we measured total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride in the serum after the oral administration of IUS.Results: 1. IUS did not show any cytotoxicity in RAW 264.7 cells. 2. IUS decreased AST, ALP, and creatinine levelsand did not show any liver or renal toxicity in the db/db mice. 3. IUS increased DPPH and ABTS radical scavenging activity and decreased ROS production in RAW 264.7 cells. 4. IUS significantly decreased IL-1β, IL-6, and TNF-α production in RAW 264.7 cells. 5. IUS increased HDL cholesterol and significantly decreased total cholesterol and triglyceride in db/db mice. 6. IUS significantly decreased the atherogenic index and cardiac risk factor. 7. In contrast with the control group, fat infiltration in the liver and aorta decreased in IUS treated mice. The cell nucleus was located in the central area in H&E staining of liver. And endomembranes also were more thinner than the control group in H&E staining of aorta.Conclusions: These results suggest that IUS might be effective in the prevention and treatment of dyslipidemia.

• Toxicological Research
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• v.26 no.4
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• pp.321-327
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• 2010

The ability of 80% ethanol extracts from five medicinal plants, Aralia continentalis, Paeonia suffruticosa, Magnolia denudata, Anemarrhena asphodeloides, and Schizonepeta tenuifolia, to neutralize hydroxyl radical, peroxyl radical and peroxynitrite was examined using the total oxyradical scavenging capacity (TOSC) assay. Peroxyl radical was generated from thermal homolysis of 2,2'-azobis(2-methylpropionamidine) dihydrochloride (ABAP); hydroxyl radical by an iron-ascorbate Fenton reaction; peroxynitrite by spontaneous decomposition of 3-morpholinosydnonimine N-ethylcarbamide (SIN-1). The oxidants generated react with $\alpha$-keto-$\gamma$-methiolbutyric acid (KMBA) to yield ethylene, and the TOSC of the substances tested is quantified from their ability to inhibit ethylene formation. Extracts from P. suffruticosa, M. denudata, and S. tenuifolia were determined to be potent peroxyl radical scavenging agents with a specific TOSC (sTOSC) being at least six-fold greater than that of glutathione (GSH). These three plants also showed sTOSCs toward peroxynitrite markedly greater than sTOSC of GSH, however, only P. suffruticosa revealed a significant hydroxyl radical scavenging capacity. Seven major active constituents isolated from P. suffruticosa, quercetin, (+)-catechin, methyl gallate, gallic acid, benzoic acid, benzoyl paeoniflorin and paeoniflorin, were determined for their antioxidant potential toward peroxynitrite, peroxyl and hydroxyl radicals. Quercetin, (+)-catechin, methyl gallate, and gallic acid exhibited sTOSCs 40~85 times greater than sTOSC of GSH. These four components also showed a peroxynitrite scavenging capacity higher than at least 10-fold of GSH. For antioxidant activity against hydroxyl radical, methyl gallate was greatest followed by gallic acid and quercetin. Further studies need to be conducted to substantiate the significance of scavenging a specific oxidant in the prevention of cellular injury and disease states caused by the reactive free radical species.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5059-5062
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• 2015

Background: ALL is an irredeemable disease due to the resistance to treatment. There are several influences which are involved in such resistance to chemotherapy, including oxidative stress as a result of the generation of reactive oxygen species (ROS) and presence of hypodiploid cells. Cluster of differentiation 26 (CD26), also known as dipeptidyl peptidase-4, is a 110 kDa, multifunctional, membrane-bound glycoprotein. Aim and objectives: The aim of this study was to evaluate the clinical significance of serum CD26 in patients with acute lymphoblastic leukaemia patients in the post remission induction phase, as well as the relationship between CD26 activity and the oxidative stress status. Materials and Methods: CD26, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI), in addition to activity of related enzymes myeloperoxidase, glutathione-s-transferase and xanthine oxidase, were analysed in sixty children with acute lymphoblastic leukaemia in the post remission induction phase. Results: The study showed significant elevation in CD26, TOS and OSI levels in patients with acute lymphoblastic leukaemia in the post remission induction phase in comparison to healthy control samples. In contrast, myeloperoxidase, glutathione-s-transferase and xanthine oxidase activities were decreased significantly. A significant correlation between CD26 concentration and some oxidative stress parameters was evident in ALL patients. Conclusions: Serum levels of CD26 appear to be useful as a new biomarker of oxidative stress in children with acute lymphoblastic leukaemia in the post remission induction phase, and levels of antioxidants must be regularly estimated during the treatment of children with ALL.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.5
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• pp.588-597
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• 2010

We investigated the effect of quercetin on growth and plasma cholesterol level and the effects of quercetin pretreatment (Diet 1, 0%; Diet 2, 0.25%; and Diet 3, 0.5% quercetin) for 30 and 60 days on oxidative stress induced by hypo-osmotic conditions (17.5, 8.75, and 4 psu) in olive flounder. The weights of flounder were higher with Diet 3 than with Diet 1 and 2, which indicated that a high concentration (Diet 3) of quercetin was very effective in growth. Total cholesterol levels were lower with Diets 2 and 3 than with Diet 1, leading us to hypothesize that quercetin removed low-density lipoproteins from circulation and thereby reduced total cholesterol. To understand the antioxidant role of quercetin, we measured the mRNA expression and activities of superoxide dismutase (SOD) and catalase (CAT) and the $H_2O_2$ concentration in quercetin-treated flounder exposed to osmotic stress. The $H_2O_2$ concentration and the SOD and CAT expression and activity levels were lower in flounder fed with Diets 2 and 3 than with Diet 1, suggesting that quercetin directly scavenges reactive oxygen species to reduce oxidative stress. Furthermore, the plasma lysozyme activity and osmolality were higher with Diets 2 and 3 than with Diet 1, indicating that quercetin increases immune function and helps to maintain physiological homeostasis. Plasma cortisol was lower with Diets 2 and 3 than with Diet 1, suggesting the quercetin protects against stress. These results indicate that quercetin has hypocholesterolemic and antioxidant effects, increases immune function, and acts to maintain physiological homeostasis.

• Journal of the Korean Society of Food Culture
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• v.24 no.6
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• pp.749-755
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• 2009

We investigated the chemical components of red onion powder dried using the low temperature vacuum method and the inhibitory effects of solvent extracts of the dried red onion powder on the growth of HT-1080 human fibrosarcoma and HT-29 human colon cancer cells and $H_2O_2$-induced oxidative stress. The moisture content of the dried red onion powder was 17.95%, while the vitamin C content was 96 mg/100 g and the total phenols content was 39.1 mg/mL. The inhibitory effects of acetone with methylene chloride (A+M) and methanol (MeOH) extracts of the red onion powder on the growth of HT-1080 and HT-29 cancer cells increased in a dose dependent manner (p<0.05). The inhibitory effect was greater on the growth of HT-29 cells, while the A+M extracts had a higher inhibitory effect than the MeOH extracts. Treatment with the hexane, 85% aq. methanol, butanol and water fractions of the extract led to significant inhibition of the growth of both cancer cell lines (p<0.05). Among the fractions, the hexane and 85% aq. methanol fractions showed a greater inhibitory effect. To determine the protective effect on $H_2O_2$-induced oxidative stress, a DCFH-DA (dichlorodihydrofluorescin diacetate) assay was conducted. All fractions, including the crude extracts of dried red onion, appeared to lead to a significant reduction in the levels of intracellular reactive oxygen species (ROS), and these reductions occurred in a dose dependent fashion (p<0.05). Among the fractions, the 85% methanol fraction showed the greatest protective effect on the production of lipid peroxides.