• 제목/요약/키워드: xanthine oxidase inhibitor

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

  • 김용식
    • 대한약리학회지
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    • 제20권1호
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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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    • 제7권3호
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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.

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

  • ;김민경;서건식;이영욱;이종수
    • 한국균학회지
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    • 제39권3호
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    • pp.185-188
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    • 2011
  • 버섯으로부터 생리 기능성이 우수한 건강 소재나 대체의약을 개발하기 위하여 백색 느티만가닥버섯의 자실체의 물추출물과 에탄올추출물을 제조한 후 이들의 생리기능성을 측정하였다. 시료 버섯 자실체의 물 추출물의 ACE 저해활성이 60.5%로 에탄올 추출물의 저해활성 보다 높았다. 또한 SOD 유사활성과 Xanthine oxidase 저해 활성도 물추출물에서 각각 24.1%와 23.0%을 보였다. 백색 느티만가닥버섯 자실체에 함유되어있는 ACE 저해 물질은 자실체 분말을 물에 1 : 40으로 현탁 시킨 후 $50^{\circ}C$에서 12시간 추출했을 때 가장 많이 추출되었고 이때 ACE 저해활성은 80.5% 이었다.

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

  • 김은경;이혜선;하홍구;윤성지;하정민;김영환;진인혜;신화경;배순식
    • 생명과학회지
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    • 제22권12호
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    • pp.1621-1627
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    • 2012
  • 세포의 이동은 성장, 면역 작용, 그리고 혈관 신생 등 많은 생리현상에 중요한 역할을 한다. 또한 염증 및 종양 세포 침윤 등의 다양한 병리적 현상과도 밀접한 연관이 있다. 본 연구에서는 lysophosphatidic acid (LPA)는 활성산소의 생성을 통해 SKOV-3 난소암세포의 이동을 조절한다는 것을 관찰하였다. 먼저, 난소 암세포인 SKOV-3에서 LPA에 의한 세포의 이동이 강하게 일어남을 확인하였다. LPA에 의한 SKOV-3 세포의 이동은 phosphatidylinositol 3-kinase (PI3K)/Akt 신호전달체계를 저해시키는 약물에 의해서 완벽히 억제됨을 확인하였으나 ERK 신호전달체계를 저해시키는 약물에 의해서는 전혀 영향을 받지 않았다. 그리고 SKOV-3 세포에서 LPA에 의한 활성산소 형성이 시간에 따라 강하게 일어남을 확인하였다. 더욱이 LPA에 의한 활성산소 형성도 PI3K 또는 Akt의 저해제에 의해서 완벽히 억제됨을 확인하였으나 ERK 신호전달을 억제하였을 때는 거의 영향을 받지 않았다. SKOV-3 세포에서 LPA에 의해 생성된 활성산소는 diphenylene idonium (DPI, $10{\mu}M$), apocyanin (Apo, $10{\mu}M$)과 같은 NADPH oxidase 억제제를 전 처리하였을 때 활성산소가 형성되지 못함을 관찰하였다. 그러나 xanthine oxidase (allopurinol, Allo, $10{\mu}M$), cyclooxygenase (indomethacin, Indo, $10{\mu}M$), 또는 mitochondrial respiratory chain complex I (rotenone, Rot, $10{\mu}M$)를 억제하였을 때는 LPA에 의한 활성산소 형성에 영향을 주지 못함을 확인하였다. 마지막으로 활성산소 억제제인 N-acetylcysteine (NAC, $10{\mu}M$)에 의해서 LPA에 의한 암세포의 이동이 억제됨을 관찰하였다. 이와 더불어 LPA에 의한 SKOV-3 세포의 이동도 NADPH oxidase 억제에 의해 저해가 됨을 확인하였다. 이러한 연구결과로 보아 LPA에 의한 활성산소의 형성에는 PI3K/Akt/NADPH oxidase 신호전달체계가 중추적인 역할을 하며 이를 통해 암세포의 이동을 조절한다는 것을 알 수 있었다.

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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    • 제27권2호
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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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    • 제3권1호
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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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    • 제46권8호
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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
    • 한국수정란이식학회지
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    • 제25권3호
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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.

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

  • 장인택;김영헌;김정한;이윤혜;주영철;이종수
    • 한국균학회지
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    • 제40권2호
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    • pp.114-117
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    • 2012
  • 버섯으로부터 새로운 생리기능성 물질을 개발을 위해 몇가지 식용 버섯들의 물 추출물들을 제조한 후 이들 추출물들의 파골세포 분화 저해활성등의 생리기능성을 측정하였다. 시료 버섯자실체들의 물 추출물 중, 느타리버섯의 물 추출물은 73.2%, 만가닥버섯은 65.3%의 비교적 높은 항고혈압성 안지오텐신 전환효소 저해활성을 보였고 느타리버섯의 물 추출물은 73.3%의 높은 항통풍성 잔틴 산화효소 저해활성을 나타내었다. 또한 만가닥버섯의 물 추출물이 21.5 mm투명환의 높은 혈전용해 활성을 보였고 잣버섯 물 추출물 역시 40.3%의 항산화 활성을 보였으나 여타의 생리기능성은 매우 미약 하였다. 또한 큰느타리버섯과 만가닥버섯의 물 추출물들은 파골세포 분화 저해활성이 높았으나, 잣버섯과 느타리버섯의 물 추출물에서는 파골세포 분화 저해활성이 없었다.

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

  • 이은호;이선호;조영제
    • Journal of Applied Biological Chemistry
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    • 제58권4호
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    • pp.317-323
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    • 2015
  • 산딸나무 열매로부터 phenolic compounds를 추출 후 생리활성을 검정하여 기능성 소재로 활용가능성을 살펴보았다. 산딸나무 열매에 함유된 페놀성 물질은 물과 40% ethanol을 용매로 하여 추출하였을 때 각각 7.04, 4.47 mg/g 함량을 나타내었다. 추출물의 phenolic 농도를 $50-200{\mu}g/mL$로 조절하여 1,1-diphenyl-2-picrylhydrazyl를 측정한 결과, 물 추출물과 ethanol 추출물 $50{\mu}g/mL$ phenolics 농도에서 각각 84, 86%였고, 2,2'-Azinobis-(3-ethylbenzothiazoline-6-sulfonic acid radical decolorization은 $100{\mu}g/mL$ phenolics 농도의 물 추출물과 ethanol 추출물에서 각각 84%, 95%였다. Antioxidant protection factor는 $50{\mu}g/mL$ phenolics 농도에서 물 추출물과 ethanol 추출물에서 각각 1.93와 1.82 PF로 측정되었으며, TBARs값은 $150{\mu}g/mL$ phenolics 농도에서 물 추출물이 69%, ethanol 추출물에서 89%를 나타내었다. Xanthine oxidase 저해능은 물 추출물과 ethanol 추출물에서 각각 34, 60%로 측정되었으며, ${\alpha}$-glucosidase 저해능은 물 추출물과 ethanol 추출물에서 각각 29, 87%의 높은 효능을 보였다. Tyrosinase 저해능을 측정한 결과 ethanol 추출물에서만 19%의 효능을 나타내었다. Collagenase 저해능 측정 결과 $200{\mu}g/mL$ phenolics 농도에서 물 추출물과 ethanol 추출물이 각각 53, 77%의 높은 저해력을 나타내어 주름개선효과가 높았다. 염증억제효과로서 hyaluronidae 저해활성을 측정한 결과, $200{\mu}g/mL$ phenolic 농도의 물 추출물에서 34%의 염증억제효과를 나타내었다. 이러한 결과로 보아 산딸나무 열매추출물은 항산화, 통풍억제, 당분해 억제, 주름개선효과, 염증억제 등의 기능성 소재로서 활용이 가능할 것으로 판단되었다.