• Title/Summary/Keyword: cyclooxygenase-1

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The Constituents Isolated from Peucedanum japonicum Thunb. and their Cyclooxygenase (COX) Inhibitory Activity

  • Zheng, Mingshan;Jin, Wenyi;Son, Kun-Ho;Chang, Hyeun-Wook;Kim, Hyun-Pyo;Bae, Ki-Hwan;Kang, Sam-Sik
    • Korean Journal of Medicinal Crop Science
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    • v.13 no.2
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    • pp.75-79
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    • 2005
  • Five coumarins, psoralen (1), scopoletin (2), isoimperatorin (4), (+)-marmesin (5) and xanthotoxin (6), three chromones, cimifugin (3), hamaudol (7) and sec-O-glucosylhamaudol (10), one sterol, daucosterol (8) and one aliphatic alcohol, galactitol (9) were isolated from the root of Peucedanum japonicum. Their chemical structures were identified by the physicochemical and spectroscopic data by comparing literature values. Among them, compounds 9 and 10 were isolated for the first time from this plant. The anti-inflammatory effects of isolated compounds were examined on cyclooxygenase (COX), compounds 1, 2 and 7 showed inhibitory activity on COX-1 with $IC_{50}$ values of 0.88, 0.27 and 0.30 mM, respectively. In the test for COX-2 activity, only compound 7 showed significant inhibitory activity with the $IC_{50}$ value of 0.57 mM. The other compounds exhibited weak inhibitory or no inhibitory activity.

Anti-tumor and Anti-inflammatory Activity of the Methanol Extracts from Adlay Bran

  • Lee, Ming-Yi;Tsai, Shu-Hsien;Kuo, Yueh-Hsiung;Chiang, Wenchang
    • Food Science and Biotechnology
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    • v.17 no.6
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    • pp.1265-1271
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    • 2008
  • Adlay bran is a waste product previously thought to have no commercial value, Its methanolic extract was fractionated using n-hexane (ABM-Hex), ethyl acetate (ABM-EtOAc), 1-butanol (ABM-BuOH), and water (ABM-$H_2O$). The ABM-EtOAc fraction exhibited a strongest inhibition against growth of human lung cancer cell A549 and human colorectal carcinoma cells HT-29 and COLO 205. Inhibition of cell cycle progression at $G_0/G_1$ transition, increase of cells at the sub-$G_1$ phase, and DNA ladders were observed in cells treated with ABM-EtOAc. The ABM-BuOH fraction showed the strongest inhibition of proinflammatory cytokines tumor necrosis factor (TNF)-$\alpha$ and interlukin (IL)-$1{\beta}$ in stimulated RAW 264.7 macrophages. Further, ABM-EtOAc and ABM-BuOH inhibited cyclooxygenase (COX)-2 expression in A549 and HT-29 carcinoma cells, while COX-l expression was not affected. These results reveal that both ABM-EtOAc and ABM-BuOH may aid the prevention of cancers and the applications in cancer chemotherapy.

(E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine inhibits Inducible Nitric Oxide Synthase Expression in RAW264.7 Macrophages Stimulated with Lipopolysaccharide

  • Gu, Gyo-Jeong;Eom, Sang-Hoon;Suh, Chang Won;Koh, Kwang Oh;Kim, Dae Young;Youn, Hyung-Sun
    • Biomedical Science Letters
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    • v.19 no.2
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    • pp.168-172
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    • 2013
  • Toll-like receptors (TLRs) play an important role for host defense against invading pathogens. TLR4 has been identified as the receptor for lipopolysaccharide (LPS), which is a cell wall component of gram-negative bacteria. The activation of TLR4 signaling by LPS leads to the activation of NF-${\kappa}B$ and the expression of pro-inflammatory gene products such as cytokines, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). To evaluate the therapeutic potential of (E)-1-(2-(2-nitrovinyl)phenyl)pyrrolidine (NVPP), previously synthesized in our laboratory, NF-${\kappa}B$ activation and iNOS and COX-2 expression induced by LPS were examined. NVPP inhibited the activation of NF-${\kappa}B$ induced by LPS. NVPP also suppressed the iNOS expression induced by LPS but it did not suppress COX-2 expression induced by LPS. These results suggest that NVPP has the specific mechanism for anti-inflammatory responses.

Mechanism of antiulceric effect of eupatilin, a biological active component of Arternisia extract

  • Miwon Son;Oh, Tae-Young;Ryu, Byung-Kweon;Moohi Yoo;Kim, Won-Bae;Junnick Yang;Lee, Eun-Bang
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1996.04a
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    • pp.198-198
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    • 1996
  • Eupatilin은 급성위궤양 모델인 HCl-EtOH model에서 0.3mg/kg에서 50% 억제하였으며 10mg/kg에서 95% 최대효과를 나타내었고, indomethacin model에서는 0.8mg/kg에서 50% 억제하였으며, 10mg/kg에서 97% 최대억제효과를 나타내었다. Cyclooxygenase-1의 활성은 1.7, 5.8$\mu\textrm{g}$/$m\ell$에서 prostaglandin E$_2$와 prostacyclin의 생성을 각각 2배 촉진시켰으나, cyclooxygenase-2에 대한 활성에는 영향을 주지 않았다. FMLP로 활성화시킨 호중구에 대한 활성은 0.6$\mu\textrm{g}$/kg에서 50% 억제하여 oxygen free radical 소거활성을 나타내었고, 반면 xanthine oxidase 및 iron-dependant lipid peroxidation 활성에 대해서는 78.8, 26.9$\mu\textrm{g}$/$m\ell$에서50% 억제를 보였다. 5-lipooxygenase 활성은 2.1$\mu\textrm{g}$/$m\ell$ 에서 염증매개인자인 leukotriene B$_4$ 생성을 50% 억제하였다. 이상의 결과로부터 애엽추출의 항궤양 효과는 prostaglandin의 생성촉진 및 oxygen free radical 과 leukotriene B4와 같은 공격인자의 생성억제 등의 복합적인 작용에 기인하는 것으로 생각된다.

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Signal Transduction Network Leading to COX-2 Induction: A Road Map in Search of Cancer Chemopreventives

  • Surh Young-Joon;Kundu Joydeb Kumar
    • Archives of Pharmacal Research
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    • v.28 no.1
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    • pp.1-15
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    • 2005
  • Cancer is still a major global health concern even after an everlasting strive in conquering this dread disease. Emphasis is now given to chemoprevention to reduce the risk of cancer and also to improve the quality of life among cancer afflicted individuals. Recent progress in molecular biology of cancer has identified key components of the cellular signaling network, whose functional abnormality results in undesired alterations in cellular homeostasis, creating a cellular microenvironment that favors premalignant and malignant transformation. Multiple lines of evidence suggest an elevated expression of cyclooxygenase-2 (COX-2) is causally linked to cancer. In response to oxidative/pro-inflammatory stimuli, turning on unusual signaling arrays mediated through diverse classes of kinases and transcription factors results in aberrant expression of COX-2. Population-based as well as laboratory studies have explored a broad spectrum of chemopreventive agents including selective COX-2 inhibitors and a wide variety of anti-inflammatory phytochemicals, which have been shown to target cellular signaling molecules as underlying mechanisms of chemoprevention. Thus, unraveling signaling pathways regulating aberrant COX-2 expression and targeted blocking of one or more components of those signal cascades may be exploited in searching chemopreventive agents in the future.

Chemopreventive effects of polysaccharides extract from Asterina pectinifera on HT-29 human colon adenocarcinoma cells

  • Nam, Kyung-Soo;Shon, Yun-Hee
    • BMB Reports
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    • v.42 no.5
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    • pp.277-280
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    • 2009
  • We examined the effects of polysaccharides extracted from Asterina pectinifera on the activities of quinone reductase (QR), glutathione S-transferase (GST), ornithine decarboxylase (ODC), cyclooxygenase (COX)-2 and glutathione (GSH) levels in HT-29 human colon adenocarcinoma cells. We found that the polysaccharides extract induced QR activity in a dose-dependent manner over a concentration range of $20-60\;{\mu}g/ml$ and increased GST activity as much as 1.4-fold over controls. GSH levels were increased 1.3- and 1.5-fold with the extract at 40 and $60\;{\mu}g/ml$, respectively. The activity and protein expression of ODC in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced colon cancer cells was inhibited by the extract. The polysaccharides suppressed TPA-induced prostaglandin (PG) production. These data indicate that polysaccharides from A. pectinifera increase phase II detoxification enzyme activity and inhibit ODC and COX-2 activities in HT-29 human colon adenocarcinoma cells. Consequently, this effect may contribute to the protective effect of polysaccharides from A. pectinifera against colon cancer.

Ethanol extract of Synurus deltoides (Aiton) Nakai suppresses in vitro LPS-induced cytokine production in RAW 264.7 macrophages and in vivo acute inflammatory symptoms

  • Jiang, Yunyao;Wang, Myeong-Hyeon
    • Nutrition Research and Practice
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    • v.8 no.1
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    • pp.11-19
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    • 2014
  • Synurus deltoides (Aiton) Nakai, belonging to the Compositae family, is an edible plant widely distributed in Northeast Asia. In this study, we examined the mechanisms underlying the immunomodulative effects of the ethanol extract of S. deltoides (SDE). The SDE extract strongly down-regulated the mRNA expression of the inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumour necrosis factor (TNF)-${\alpha}$, thereby inhibiting the production of nitric oxide (NO), prostaglandin E2 (PGE2), and TNF-${\alpha}$ in the lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Furthermore, SDE also suppressed the nuclear translocation of the activation protein (AP)-1 and the nuclear factor-${\kappa}B$ (NF-${\kappa}B$), and simultaneously decreased the phosphorylation of extracellular signal-regulated protein kinases (ERK), p38, and Akt. In agreement with the in vitro observations, the orally administered SDE ameliorated the acute inflammatory symptoms in the arachidonic acid-induced ear edema and the EtOH/HCl-induced gastritis in mice. Therefore, S. deltoides have a potential anti-inflammatory capacity in vitro and in vivo, suggesting the potential therapeutic use in the inflammation-associated disorders.

Diphlorethohydroxycarmalol, Isolated from Ishige okamurae, Increases Prostaglandin E2 through the Expression of Cyclooxygenase-1 and -2 in HaCaT Human Keratinocytes

  • Kang, Gyeoung-Jin;Han, Sang-Chul;Koh, Young-Sang;Kang, Hee-Kyoung;Jeon, You-Jin;Yoo, Eun-Sook
    • Biomolecules & Therapeutics
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    • v.20 no.6
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    • pp.520-525
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    • 2012
  • Prostaglandin (PG) $E_2$, the most abundant prostaglandin in the human body, is synthesized from arachidonic acid via the actions of cyclooxygenase (COX) enzymes. $PGE_2$ exerts homeostatic, cytoprotective, inflammatory, and in some cases anti-inflammatory effects. Also, it has been reported that $PGE_2$ is involved in hair growth. Diphlorethohydroxycarmalol (DPHC) is a phlorotannin compound isolated from the brown algae Ishige okamurae, with various biological activities in vitro and in vivo. In this study, the biological effect and mechanism of action of DPHC on prostaglandin synthesis in HaCaT human keratinocytes was examined. The results showed that, in these cells, DPHC significantly and dose-dependently induced $PGE_2$ synthesis by increasing the protein and mRNA levels of COX-1 and COX-2. Interestingly, DPHC-induced COX-1 expression preceded that of COX-2. Also, while both rofecoxib and indomethacin inhibited $PGE_2$ production, the latter was seems to be the more potent. From above results, we can expect that DPHC has some beneficial effects via increasing of $PGE_2$ production.

Deep Vein Thrombosis in Advanced Cervical Cancer Patient after Taking Cyclooxygenase-2 Selective Inhibitors (Cyclooxygenase-2 선택적 억제제를 복용 중 자궁암 환자에 발생한 심부정맥혈전증 1예)

  • Ko, Byung-Joon;Kim, Su-Hyun;Kim, Jeong-A;Hong, Jeong-Ik;Yoon, Do-Kyoung;Kim, Jung-Hwan;Sohn, Keun-Ju;Choi, Youn-Seon
    • Journal of Hospice and Palliative Care
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    • v.8 no.1
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    • pp.57-64
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    • 2005
  • Cyclooxygenase-2 (COX-2) selective inhibitors were specifically developed to reduce the risks of gastrointestinal bleeding associated with other NSAID drugs. However, the APPROVe (Adenomatous Polyp Prevention on VIOXX) trials revealed that rofecoxib sometimes exerts prothrombotic effects. Meanwhile, cancer patients, who also carry a risk of thrombosis due to a variety of mechanisms, are often treated with COX-2 selective inhibitors, due to their relative gastrointestinal safety. This report concerns the case of a 46-year old woman with advanced cervical cancer, who had been treated with opioids and a COX-2 selective inhibitor (celecoxib) for 2 months, for the relief of pain associated with her cancer. The patient was admitted due to swelling of the left leg, which was also accompanied by pain. A computerized tomography scan revealed deep vein thrombosis occurring in multiple veins of both legs. After the administration of low-molecular weight heparin and oral warfarin, the patient's symptoms were relieved initially. However, her prothrombin time was found to be prolonged, necessitating the discontinuation of anticoagulation therapy. The patient's dyspnea worsened, ultimately resulting in her death. In conclusion, the administration of cox-2 selective inhibitors should be carefully considered in patients with a number of different risk factors, and assessed on a case-by-case basis.

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