• Title/Summary/Keyword: cyclooxygenase-1

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New Insights in Arachidonate Cascade: Biochemical Characterization and Biological Significance of Three Distinct Prostaglandin E Synthases

  • Kudo, Ichiro
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.111-113
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    • 2003
  • Biosynthsis of prostaglandin E2 (PGE2), the most common prostanoid with potent and diverse bio-activities, is regulated by three sequential enzymatic steps composed of phospholipase A2, cyclooxygenase (COX), and prostaglandin E synthase (PGES). Recently, three distinct PGESs have been identified; two of them are membrane-bound enzymes, mPGES-1 and mPGES-2, and the third one is a cytosolic enzyme, cPGES. (omitted)

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CELECOXIB INHIBITS PHORBOL ESTER-INDUCED PGE$_2$ PRODUCTION AND COX-2 EXPRESSION BY TARGETING OF p38 MAP KINASE AND AP-1 IN MOUSE SKIN

  • Chun, Kyung-Soo;Surh, Young-Joon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.175-175
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    • 2002
  • Celecoxib, a selective COX-2 inhibitor, has been reported to prevent experimentally induced colon, breast, bladder, and skin carcinogenesis. Moreover, daily intake of celecoxib resulted in significant reduction of polyps in patients with familial adenomatous polyposis.(omitted)

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PROINFLAMMATORY DAMAGE INDUCED IN RAT STOMACH BY INTRAGASTRIC ETHANOL ADMINISTRATION

  • Lee, Jeong-Sang;Oh, Tae-young;Surh, Young-Joon
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.154-154
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    • 2002
  • Several lines of epidemiological and experimental evidence support that chronic ethanol consumption is implicated in pathophysiology of a variety of human disorders, including cancer. However, the association between chronic ethanol consumption and an increased risk of gastric cancer is not clearly defined.(omitted)

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Celecoxib Attenuates Nitric Oxide-Induced Apoptosis in PC12 Cells by Inhibiting AP-1 Activation and COX-2 Expression.

  • Li, Mei-Hua;Jang, Jung-Hee;Surh, Young-Joon
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.143.2-144
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    • 2003
  • Recent studies suggest that inflammatory events are implicated in a variety of ailments such as cancer and neurodegenerative diseases, and certain non-steroidal anti-inflammatory drugs have beneficial effects for the treatment or prevention of these disorders. Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the prostaglandin (PG) synthesis, is induced by various pro-inflammatory stimuli including nitric oxide (NO) and has been reported to cause and/or aggravate neuronal cell death. (omitted)

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Analgesic Action Mechanism of DA-5018, a New Capsaicin Derivative : Relationship to Opiate :Receptors and Prostanoids (새로운 캅사이신 유도체 DA-5018의 진통활성 기전연구: Opiate 수용체 및 :Prostanoid와의 상관성)

  • 손미원;손문호;배은주;김순희;김원배;양중의
    • Biomolecules & Therapeutics
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    • v.5 no.1
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    • pp.87-93
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    • 1997
  • DA-5018, a new capsaicin derivative, showed potent analgesic effect comparable to that of morphine in various experimental acute pain models. in this study, whether the analgesic mechanism of DA-5018 is related to opiate receptors or prostanoids was investigated. The affinity of DA-5018 for opiate receptor was determined by receptor binding assay. The Ki values of DA-5018 for nonspecific and specific $\mu$, $textsc{k}$, $\delta$-opiate receptor was 299$\pm$8.88, 735$\pm$215, 2930$\pm$ 163, 1550$\pm$813 nM, respectively and DA-5018 exhibited lower affinity than morphine. DA-5018 (10-"~3$\times$10-′M) inhibited electrically-evoked contractions of the guinea ply ileum and rat vas deferens, and these inhibition was not antagonized by naloxone(10 nM), an opiate receptor antagonist. Antagonism of analgesic effect of 7A-5018 by naloxone was examined by tail pinch test. Analgesic action of DA-5018(0.1 ~2 mg/kg, 5.c.) was not antagonized by naloxone(1 mg/rg, i.p.). These results indicate that pharmacological action of DA-5018 is not related with opiate receptor. Cyclooxygenase and 5-lipoxygenase activities in rat peritoneal neutrophil treated with A23187 and arachidonic acid were measured by radioimmunoassay. DA-5018 stimulated the cyclooxygenase activity and the concentration show-ing the two fold increase of activity was 124$\mu$M. DA-5018 slightly inhibited 5-lipoxygenase activity and these results together indicate that analgesic action of 3A-5018 is not mediated through inhibition of cyclooxy genase or lipoxygenase. These results suggest that the analgesic effect of DA-5018 is not due to blocking opiate receptor or to inhibiting the synthesis of prostanoids in the arachidonic acid metabolism pathway.

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The Effects of Perpendicular Needling Laogong ($PC_8$) on the Improvement of Cerebral Hemodynamics in Rats (노궁(勞宮)($PC_8$) 직자(直刺)가 백서(白鼠)의 뇌혈류력학(腦血流力學)에 미치는 영향)

  • Heo, Jin;Kim, Jung-Ho;Kim, Young-Il
    • Journal of Acupuncture Research
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    • v.28 no.4
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    • pp.19-35
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    • 2011
  • Objectives : This study was designed to investigate the effects of acupuncturing $PC_8$ used perpendicular needling method determine the mechanism of action of acupuncturing $PC_8$ by measuring the changes of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in normal rats. Methods : This study also investigated the effects of acupuncturing $PC_8$ on the change of rCBF in cerebral ischemic rats, and revealed the mechanism of its action. In addition, the effects of acupuncturing $PC_8$ on focal ischemic brain injury was studied in cerebral ischemic rats. Results : 1. Acupuncturing $PC_8$ significantly increase rCBF but decreased MABP in normal rats. 2. Acupuncturing $PC_8$ increased of rCBF was significantly inhibited by pretreatment with indomethacin (1mg/kg, i.p.), an inhibitor of cyclooxygenase in normal rats. 3. Acupuncturing $PC_8$ increased of rCBF was significantly inhibited by pretreatment methylene blue (10 ${\mu}g$/kg, i.p.), an inhibitor of guanylate cyclase in normal rats. 4. Acupuncturing $PC_8$ was significantly improved the rCBF than control group increased unstable in cerebral ischemic rats. 5. Acupuncturing $PC_8$ was not significantly improved the rCBF than control group by pretreatment with indomethacin (1mg/kg, i.p.), an inhibitor of cyclooxygenase in cerebral ischemic rats. 6. Acupuncturing $PC_8$ was significantly increased the rCBF than control group by pretreatment methylene blue ($10{\mu}g$/kg, i.p.), an inhibitor of guanylate cyclase in cerebral ischemic rats. Conclusions : In conclusion, our study suggested that acupuncturing $PC_8$ can increase rCBF in normal state, and improve stability of rCBF in ischemic state. In addition, we suggested that mechanisms related with acupuncturing $PC_8$ was involved in the guanylate cyclase pathway.

Antiplatelet Effects of Cordycepin-Enriched WIB-801CE from Cordyceps militaris: Involvement of Thromboxane A2, Serotonin, Cyclooxygenase-1, Thromboxane A2 Synthase, Cytosolic Phospholipase A2

  • Ok, Woo Jeong;Nam, Gi Suk;Kim, Min Ji;Kwon, Hyuk-Woo;Kim, Hyun-Hong;Shin, Jung-Hae;Lim, Deok Hwi;Kwon, Ho-Kyun;Lee, Chang-Hwan;Chung, Soo-Hak;Kim, Jong-Lae;Park, Hwa-Jin
    • Biomedical Science Letters
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    • v.22 no.4
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    • pp.127-139
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    • 2016
  • A species of the fungal genus Cordyceps has been used as an ingredient of traditional Chinese medicine. In this study, we prepared cordycepin-enriched WIB-801CE, an ethanol extract from culture solution of Cordyceps militaris-hypha, and evaluated its antiplatelet effects on human platelet aggregation. WIB-801CE dose-dependently inhibited ADP-, collagen-, and thrombin-induced platelet aggregation. These antiplatelet effects by WIB-801CE were associated with the attenuation of thromboxane $A_2$ ($TXA_2$) production and serotonin release by ADP, collagen, and thrombin. The inhibition of $TXA_2$ production by WIB-801CE was due to the inhibition of cyclooxygenase-1, $TXA_2$ synthase, and cytosolic phospholipase $A_2$ activity. Therefore, these data suggest that WIB-801CE may be a beneficial component against protection from platelet aggregation-mediated thrombotic disease.

Screening of Arachidonic acid Cascade Related Enzymes Inhibitors from Korean Indigenous Plants(1) (한국 자생식물로부터 아라키돈산 대사계 효소 저해제 검색(1))

  • Moon, Tae-Chul;Jung, Hye-Jin;Lee, Eun-Kyung;Park, Hae-Young;Jeon, Su-Jin;Son, Kun-Ho;Kim, Hyun-Pyo;Bae, Ki-Hwan;Kang, Sam-Sik;Kwon, Dong-Yeul;Chang, Hyeun-Wook
    • Korean Journal of Pharmacognosy
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    • v.34 no.1 s.132
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    • pp.109-117
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    • 2003
  • Arachidonic acid(AA), which is stored in membrane glycerophospholipids, is liberated by phospholipase $A_2(PLA_2)$ enzymes and is sequentially converted to cyclooxygenase (COX) and lipoxygenase (LOX) then to various bioactive prostaglandins (PGs,) and leukotrienes (LTs). In order to find the specific inhibitors of AA metabolism enzymes such as $PLA_2$, COX-2, 5-LO and lyso PAF acetyltransferase. 195 Korean indigenous plant extracts were evaluated for their inhibitory activity on $PGD_2,\;LTC_4$ production from cytokine-induced mouse bone marrow-derived mast cells (BMMC) and arachidonic acid released from phospholipid and PAF production from lyso PAF. From this screening procedure, methanol extract of eight plants such as Saururus chinensis, Aster tataricus, Chrysanthemum cinerariaefolium, Reynoutria japonica, Disocorea nipponica, Epimedium koreanum, impatiens textori, Veronica rotunda var. subintegra were found to inhibit production of inflammatory mediators in vitro assay system.

The Regulatory Effect of Zhengan Xifeng-tang on Pro-inflammatory Cytokine in Human Brain Astrocytes (인간 뇌 성상세포에서 진간식풍탕의 사이토카인 조절 효과)

  • Ryu Hyun Hee;Lee Seoung Geun;Lee Key Sang
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.2
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    • pp.490-495
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    • 2004
  • Brain cells produce cytokines and chemokines during the inflammatory process of many neuronal diseases both in animal models and in patients. Inflammatory cytokines are the main responsible for the onset of inflammatory cascade. During the past decade, a growing corpus of evidence has indicated an important role of these cytokines in the development of brain damage. ZhenganXifeng-tang (ZGXFT) is a Korean herbal prescription, which has been successfully applied for the treatment of various neuronal diseases. However, its effect in experimental models remains unknown. Astrocytes are predominant neuroglial cells of the central nervous system and are actively involved in cytokine-mediated events in inflammatory disease. An inflammatory response associated with β-amyloid (Aβ) and interleukin (IL)-1β is responsible for the pathology of inflammation disease. To investigate the biological effect of ZGXFT, the author examined cytotoxicity, effect of cytokines (IL-6 and IL-8) secretion and expression of cyclooxygenase-2 (COX-2) on human astrocytoma cell line U373MG stimulated with IL-1β plus M fragment 25-35 (Aβ [25-35]). ZGXFT by itself had no effect on cell viability on human astrocytoma cells. The secretion of IL-6 and IL-8 was inhibited by pre-treatment with ZGXFT in human astrocytoma cells. In addition, the expression of COX-2 was induced by IL-1β plus AB[25-35] and was partially inhibited by treatment with ZGXFT. The author demonstrates the regulatory effects of inflammatory reactions by ZGXFT in human astrocytes for the first time and suggest the anti-inflammatory effect of ZGXFT may reduce and delay pathologic events of inflammatory disease.