• Title/Summary/Keyword: xanthine oxidase inhibitor

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Effect of Ascorbic Acid on the Activities of Ethanol Metabolizing Enzymes (Ascorbic acid가 에탄올 대사효소에 미치는 영향)

  • Kim Yong-Sik
    • The Korean Journal of Pharmacology
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    • v.20 no.1 s.34
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    • pp.47-54
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    • 1984
  • Effect of ascorbic acid on various hepatic ethanol metabolizing enzymes including alcohol dehydrogenase(ADH), the microsomal . ethanol oxidizing system(MEOS), and catalase was quantitatively evaluated in liver microsomal and cytosolic preparation from Sprague-Dowley rats. In present study, ADH activities were no changed significantly by ascorbic acid. The MEOS activity, dependent on NADPH and $O_2$, was affected by azide (inhibitor of catalase) or exogenous catalase. In the presence of ascorbic acid, ethanol oxidation by rat liver microsomal preparation reacted with NADPH-generating system was increased by up to 22.5%, but decreased when liver microsome was reacted with $H_2O_2$ generated by xanthine and xanthine oxidase. Increase in the activity of the MEOS in the presence of ascorbic acid was greater in liver microsomal preparation pretreated with azide. Also ascorbic acid oxidized ethanol nonenzymatically. This ethanol oxidation induced by ascorbic acid was inhibited by OH radical scavengers (thiourea, sodium benzoate), but was not much affected by superoxide dismutase. From these results it was suggested that ascorbic acidcould interact directly with the MEOS, then promote the oxidation of ethanol. And, to some extent, ${\cdot}OH$-radicals or other radicals generated during the spontaneous autooxidation of ascorbic acid may be responsible for the production of acetaldehyde from ethanol.

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Physiological and Functional Properties of Salicornia herbacea (Tungtungmadi) Leaf Extracts

  • Min, Jin-Gi;Son, Kwang-Tae;Kim, Ji-Hoe;Kim, Tae-Jin;Park, Jeong-Heum
    • Preventive Nutrition and Food Science
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    • v.7 no.3
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    • pp.261-264
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    • 2002
  • The physiologically relevant functional properties of various solvent extracts from Salicornia herbacea leaves were investigated by measuring lipid peroxidation, DPPH radical scavenging, nitrite scavenging, and xanthine oxidase inhibition. Ethyl ether, chloroform, ethyl acetate and n-butanol fractions obtained from the 80% aqueous ethanol extracts of Salicornia herbacea leaves showed strong antioxidative activities in linoleic acid methyl esters. Peroxide values (POV) were not significantly different among the samples treated with the different fractions; the incubation time required to reach a peroxide value of 80 meq/kg was about 40 hrs. However, control linoleic acid methyl esters had POV of more than 480 meq/kg after 40 hrs. The DPPH radical scavenging activity of the ethyl acetate fraction was much more effective than diethyl ether, n-butanol, chloroform and water fractions, with an $IC_{50}$/ of 279 $\mu\textrm{g}$/mL, but less effective than ascorbic acid ($IC_{50}$/ : 67 $\mu\textrm{g}$/mL). The nitrite scavenging activities of all fractions increased as pH decreased. Among the fractions, nitrite scavenging activities of diethyl ether and ethyl acetate fractions at pH 1.2 were highest at 59.0 and 56.2%, respectively. The diethyl ether fraction obtained from the 80% aqueous ethanol extract of Salicornia herbacea loaves was the most effective inhibitor of xanthine oxidase of all the solvent extracts at 84% inhibition for a 1 mg/mL concentration. These results suggest that Salicornia herbacea leaf extracts may be effective antioxidants, not only in food stability, but also in human health.

Screening and Physiological Functionality of Hypsizygus marmoreus (White Cultivar) Fruiting Body (백색 느티만가닥버섯 자실체의 생리기능성 탐색)

  • Bolormaa, Zanabaatar;Kim, Min-Kyung;Seo, Geon-Sik;Lee, Young-Wook;Lee, Jong-Soo
    • The Korean Journal of Mycology
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    • v.39 no.3
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    • pp.185-188
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    • 2011
  • To develop health food and alternative medicine, water and ethanol extracts from Hypsizygus marmoreus (white cultivar) fruiting body were prepared, and its physiological functionalities were investigated. Antihypertensive angiotensin I-converting enzyme (ACE) inhibitor activity from water extract was showed higher of 60.5% than ethanol extract and SOD-like activity and xanthine oxidase inhibitory activity were also showed 24.1% and 23.0%, respectively. The other functionalities were very low or not detected. The maximal ACE inhibitory activity (80.5%) was obtained when the fruiting body of Hypsizygus marmoreus was extracted with distilled water (dilution 1 : 30) at $50^{\circ}C$ for 12 h.

Reactive Oxygen Species Mediates Lysophosphatidic Acid-induced Migration of SKOV-3 Ovarian Cancer Cells (SKOV-3 난소암 세포주에서 lysophosphatidic acid 유도 세포의 이동에 있어 활성산소의 역할)

  • Kim, Eun Kyoung;Lee, Hye Sun;Ha, Hong Koo;Yun, Sung Ji;Ha, Jung Min;Kim, Young Whan;Jin, In Hye;Shin, Hwa Kyoung;Bae, Sun Sik
    • Journal of Life Science
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    • v.22 no.12
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    • pp.1621-1627
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    • 2012
  • Cell motility plays an essential role in many physiological responses, such as development, immune reaction, and angiogenesis. In the present study, we showed that lysophosphatidic acid (LPA) modulates cancer cell migration by regulation of generation of reactive oxygen species (ROS). Stimulation of SKOV-3 ovarian cancer cells with LPA strongly promoted migration. but this migration was completely blocked by pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Inhibition of the ERK pathway had no effect on migration. Stimulation of SKOV-3 ovarian cancer cells with LPA significantly induced the generation of ROS in a time-dependent manner. LPA-induced generation of ROS was significantly blocked by pharmacological inhibition of PI3K or Akt, but inhibition of the ERK signaling pathway had little effect. LPA-induced generation of ROS was blocked by pretreatment of SKOV-3 ovarian cancer cells with an NADPH oxidase inhibitor, whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I had no effect. Scavenging of ROS by N-acetylcysteine completely blocked LPA-induced migration of SKOV-3 ovarian cancer cells. Inhibition of NADPH oxidase blocked LPA-induced migration whereas inhibition of xanthine oxidase, cyclooxygenase, or mitochondrial respiratory chain complex I did not affect LPA-induced migration of SKOV-3 ovarian cancer cells. Given these results, we suggest that LPA induces ROS generation through the PI3K/Akt/NADPH oxidase signaling axis, thereby regulating cancer cell migration.

Antioxidants and Inhibitor of Matrix Metalloproteinase-1 Expression from Leaves of Zostera marina L

  • Kim, Jin-Hui;Cho, Young-Ho;Park, Sung-Min;Lee, Kyung-Eun;Lee, Jeong-Jae;Lee, Bum-Chun;Pyo, Hyeong-Bae;Song, Kyung-Sik;Park, Hum-Dai;Yun, Yeo-Pyo
    • Archives of Pharmacal Research
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    • v.27 no.2
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    • pp.177-183
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    • 2004
  • In order to develop new anti-photoaging agents, we examined the antioxidative activity and the inhibition effect of matrix metalloproteinase-1 (MMP-1) on the extracts of a marine product, Zostera marina L., which is known for its potent activity. Three compounds (compounds 1, 2, and 3) were isolated from an ethyl acetate (EtOAc) soluble fraction of the product; they were identified as apigenin-7 -O-$\beta$-D-glucoside (1), chrysoeriol (2), and luteolin (3). These compounds were found to scavenge radicals and reactive oxygen species (ROS) and were measured to have $SC_{50}$/ values of 0.18 mM, 0.68 mM, and 0.01 mM against the 1, 1-diphenyl-2-picrylhydrazyl (DPPH) radical and 0.04 mM, 0.03 mM, and 0.01 mM against the superoxide radical in the xanthine/xanthine oxidase system, respectively. Compound 3 suppressed the expression of MMP-1 by up to 44% at 4.0 $\mu$M and inhibited the production of interleukin 6 (IL-6), which is known as a cytokine that induces MMP-1 expression. From these results, compound 3 and the other compounds were determined to have antioxidative activity and to inhibit MMP-1 expression. Thus, the three compounds are expected to be useful for preventing the photoaging of skin.

Effect of Allopurinol on the Ethanol-induced Oxidative Stress : Mechanism of Allopurinol Action

  • Park, Min-Kyung
    • Preventive Nutrition and Food Science
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    • v.3 no.1
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    • pp.48-55
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    • 1998
  • An acute ethanol load(50mmol/kg , i.p) resulted in an increase in peroxidation and a decrease in the levels of $\alpha$-tocopherol and ascorbate in rat cerebellum. Pretreatement with allopurinol(146$\mu$mol/kg, i.p) prevented the ethnol-induced increment in lipid peroxidation and decrease in $\alpha$-tocopherol content. However, the decrease of ascorbate was of greater magnitude when allopurinol was associated with ethanol. These results suggested that allopurinol. besides its action as a radical scavenger and xanthine oxidase inhibitor, might favor the regeneration of $\alpha$-tocopherol antioxidant acitviity was studied using ${\gamma}$-radiolysis in aerated ethanolic solutions. Even though allopurinol did not react by itself with $\alpha$-hydroxyethyl-peroxyl radicals [H3C-CH(OH)OO] , it enhance the $\alpha$-hydroxyethyl-peroxyl radical scavenging properties of $\alpha$tocopherol. The regeneration of $\alpha$-tocopherol from the $\alpha$-hydroxyethyl-peroxyl radical scavenging properties of $\alpha$-tocophero. The regeneration of $\alpha$-tocopherol from the $\alpha$-tocopherol radical by ascorbate remained as efficient in the presence of allopurinol as in its absence. The effects of allopurinol on the Vitamin E oxidation-reduction mechanism could be involoved in the beneficial effectof allopurinol on the biological cellular damages linked to free radical reactions.

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CD38 Inhibition Protects Fructose-Induced Toxicity in Primary Hepatocytes

  • Soo-Jin Lee;Sung-E Choi;Seokho Park;Yoonjung Hwang;Youngho Son;Yup Kang
    • Molecules and Cells
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    • v.46 no.8
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    • pp.496-512
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    • 2023
  • A fructose-enriched diet is thought to contribute to hepatic injury in developing non-alcoholic steatohepatitis (NASH). However, the cellular mechanism of fructose-induced hepatic damage remains poorly understood. This study aimed to determine whether fructose induces cell death in primary hepatocytes, and if so, to establish the underlying cellular mechanisms. Our results revealed that treatment with high fructose concentrations for 48 h induced mitochondria-mediated apoptotic death in mouse primary hepatocytes (MPHs). Endoplasmic reticulum stress responses were involved in fructose-induced death as the levels of phosho-eIF2α, phospho-C-Jun-N-terminal kinase (JNK), and C/EBP homologous protein (CHOP) increased, and a chemical chaperone tauroursodeoxycholic acid (TUDCA) prevented cell death. The impaired oxidation metabolism of fatty acids was also possibly involved in the fructose-induced toxicity as treatment with an AMP-activated kinase (AMPK) activator and a PPAR-α agonist significantly protected against fructose-induced death, while carnitine palmitoyl transferase I inhibitor exacerbated the toxicity. However, uric acid-mediated toxicity was not involved in fructose-induced death as uric acid was not toxic to MPHs, and the inhibition of xanthine oxidase (a key enzyme in uric acid synthesis) did not affect cell death. On the other hand, treatment with inhibitors of the nicotinamide adenine dinucleotide (NAD)+-consuming enzyme CD38 or CD38 gene knockdown significantly protected against fructose-induced toxicity in MPHs, and fructose treatment increased CD38 levels. These data suggest that CD38 upregulation plays a role in hepatic injury in the fructose-enriched diet-mediated NASH. Thus, CD38 inhibition may be a promising therapeutic strategy to prevent fructose-enriched diet-mediated NASH.

Effects of Cumulus Cells and Reactive Oxygen Species (ROS) on Plasminogen Activator Activity during In Vitro Maturation of Porcine Oocytes

  • Sa, Soo-Jin;Park, Chun-Keun;Kim, In-Cheul;Lee, Seung-Hoon;Kwon, Oh-Sub;Kim, Myung-Jick;Cho, Kyu-Ho;Kim, Du-Wan;So, Kyoung-Min;Cheong, Hee-Tae;Webb, Bob
    • Journal of Embryo Transfer
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    • v.25 no.3
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    • pp.171-177
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    • 2010
  • Plasminogen activators (PAs) are serine proteases that convert plasminogen to plasmin. The PA/plasmin system has been associated with a number of physiological processes such as fibrinolysis, ovulation and fertilization. Although correlations have been reported between reactive oxygen species (ROS) and oocyte maturation, the relationship between PA activity and ROS is unknown. The present study was undertaken to determine the effects of cumulus cells on PA activity in matured porcine oocytes under xanthine (X)-xanthine oxidase (XO) system. When oocytes were matured under the X-XO system, the proportion of oocytes remaining GV stage was higher (p<0.05) in oocytes without cumulus cells. The incidence of degenerated oocytes was higher (p<0.05) in the X+XO ($11.1{\pm}6.1$ and $21.6{\pm}3.4%$) than in the control group ($2.9{\pm}1.8$ and $4.0{\pm}1.6%$). The proportion of TUNEL-positive oocytes and activity of caspase-3 were higher (p<0.05) in cumulus-free oocytes and oocytes exposed to ROS. Tissue-type plasminogen activator-plasminogen activator inhibitor (tPA-PAI) and tissue-type plasminogen activator (tPA) activity were detected in oocytes that were separated from cumulus-oocytes complexs (COCs) at 44 h of maturation culture, and only tPA was produced in oocytes that were denuded before the onset of maturation culture. On the other hand, the activities of PA were increased (p<0.05) when oocytes were cultured under the X-XO system. The higher activity of tPA was observed in denuded oocytes (DOs) underwent apoptotic changes by oxidative stress. In COCs, however, tPA-PAI as well as tPA activity was detected and apoptotic changes such as DNA cleavage or caspase-3 activation were not observed. These results suggest that tP A may be relevant to apoptotic cell death in porcine oocytes by oxidative stress.

Screening of Bioactive Compounds from Edible Mushroom and Production of Anti-osteoporosis Osteoclast Differentiation Inhibitor (몇 가지 주요 식용버섯의 생리기능성 물질 탐색과 파골세포 분화 저해물질의 생산)

  • Jang, In-Taek;Kim, Young-Hun;Kim, Jeong-Han;Lee, Yun-Hae;Ju, Young-Cheoul;Lee, Jong-Soo
    • The Korean Journal of Mycology
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    • v.40 no.2
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    • pp.114-117
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    • 2012
  • For development of new bioactive compounds from main edible mushrooms, we determined some physiological functionalities of water extracts from mushrooms. Among water extracts from some mushroom fruiting bodies, water extracts from Pleurotus ostreatus showed 73.2% of anti-hypertensive angiotensin I-converting enzyme inhibitory activity and 73.3% of anti-gout xanthine oxidase inhibitory activity, respectively. Fibrinolytic activity was also showed 21.5 mm of clear zone in water extract of Lyophyllum cinerascens. However, the other physiological functionalities were very weaked except 40.3% of antioxidant activity in Lentinus lepideus. Furthermore, the water extracts of Pleurotus eryngii and Lyophyllum cinerascens showed high anti-osteoporosis osteoclast differentiation inhibitory activity. However, the water extract from Lentinus lepideus and Pleurotus ostreatus were not detected any osteoclast differentiation inhibitory activity.

Biological Activities of Extracts from Cornus kousa Fruit (산딸나무(Cornus kousa) 열매 추출물의 생리활성)

  • Lee, Eun-Ho;Lee, Seon-Ho;Cho, Young-Je
    • Journal of Applied Biological Chemistry
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    • v.58 no.4
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    • pp.317-323
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    • 2015
  • The extracted phenolic compounds from Cornus kousa fruit for biological activities as functional resources were examined. The phenolic compounds which were extracted with water and 40% ethanol from Cornus kousa fruit were $7.04{\pm}0.27$ and $4.47{\pm}0.18mg/g$, respectively. The 1,1-diphenyl-2-picrylhydrazyl free radical scavenging activity of water and ethanol extracts were 84% and 86% at $50{\mu}g/mL$phenolics, respectively. The 2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid radical decolorization activity of water and ethanol extracts were 84 and 95% at $100{\mu}g/mL$ phenolics, respectively. Antioxidant protection factor in water and ethanol extracts at $50{\mu}g/mL$ phenolics were 1.93 and 1.82 PF, respectively. Thiobarbituric acid reactive substance were 69% in water extracts and 89% in ethanol extracts at $150{\mu}g/mL$ phenolics. The inhibition activity on xanthine oxidase in water and ethanol extracts was 34 and 60%, respectively. The inhibition activity on ${\alpha}$-glucosidase was 29% in water extracts and 87% in ethanol extracts. The tyrosinase inhibitory activity was 19% in ethanol extracts. The collagenase inhibition activity of anti-wrinkle effect showed an excellent wrinkle improvement effect as 53% in water extracts and 77% in ethanol extracts at $200{\mu}g/mL$ phenolics. The hyaluronidase inhibition activity as antiinflammation effect of water extracts was confirmed to 34% of inhibition at $200{\mu}g/mL$ phenolic. The results can be expected extracts from Cornus kousa fruit to use as functional resource for antioxidant, antigout, inhibitor of carbohydrate degradation, antiwrinkle activity and antiinflammation activity.