• Title/Summary/Keyword: Cyclooxygenase 2

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Lack of Association of the Cyclooxygenase-2 Gene 8473T>C Polymorphism with Breast Cancer Risk: a Meta-analysis

  • Yang, Xi;Zhao, Fen;Li, Yue-Hua;Huang, Min;Huang, Ying;Yi, Cheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9693-9698
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    • 2014
  • Background: Associations between the 8473T>C polymorphism (rs5275) in the cyclooxygenase-2 (COX-2) gene and breast cancer (BC) risk are still inconclusive and ambiguous. The aim of this meta-analysis was to comprehensively estimate the genetic risk of 8473T>C polymorphism in the COX-2 gene for BC. Materials and Methods: We searched PubMed, Web of Science, Medline, Chinese biomedical (CBM), Weipu, China national knowledge infrastructure (CNKI), and Wanfang databases, covering all publications (last search was updated on Aug 17, 2014). Statistical analyses were performed using Revman 5.3 and STATA 10.0 software. Results: A total of 6,720 cases and 9,794 controls in 12 studies were included in this study. The results indicated no significant associations between the 8473T>C polymorphism of the COX-2 gene and BC risk for the CC+TC vs TT model (pooled odds ratio (OR)=0.97, 95% confidence interval (CI)=0.90-1.03, and p=0.29). On subgroup analysis, we also found that subdivision on ethnicity among Caucasians, Asians and others also revealed no relationship with BC susceptibility. With the study design (CC+TC vs TT), no significant associations were found in either population-based case-control studies (PCC), or hospital-based case-control studies (HCC). Conclusions: This present meta-analysis suggests that the 8473T>C polymorphism in the COX-2 gene is not a conspicuous low-penetrant risk factor for developing BC.

Inhibition of Inducible Nitric Oxide Synthase and Cyclooxygenase-2 by Gamijihwang-tang Via Suppression of Nuclear Factor-B Activation in RAW 264.7 cells

  • Jang Du-Hyun;Kim Ji-Young;Han Eun-Hee;Park Hee-Ok;Kim Dong-Hee;Jeong Hye-Gwang;Yoo Dong-Yeol
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.19 no.5
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    • pp.1405-1410
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    • 2005
  • Asthma is recognized today as an inflammatory disease of the lung characterized by acute non-specific airway hypersensitiveness in association with chronic pulmonary inflammation. Gamijihwang-tang(GJT), a fortified prescription of YMJHT, is applied for the treatments of chronic coughing and asthma, and post-delivery coughing and asthma in the gynecology. Also in the clinical practice, GJT is known to be very effective for controlling coughing and asthma as a cold sequoia. In this study, we investigated the effects of GJT on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production, and on the level of inducible nitric oxide synthase (iNOS) and Cyclooxygenase-2 expression in murine macrophage RAW 264.7 cells. We found that GJT inhibited LPS-induced NO and $PGE_2$ production in a dose dependent manner. Furthermore, GJT inhibited the expression of LPS-induced iNOS and COX-2 protein and mRNA expression in RAW 264.7 macrophages. Treatment with GJT of RAW 264.7 cells transfected with a reporter construct indicated a reduced level of LPS-induced nuclear factor-KB (NF-kB) activity and effectively lowered NF-kB binding as measured by transient transfection assay. These results suggest that the main inhibitory mechanism of the GJT may be the reduction of iNOS and COX-2 gene expression through blocking of NF-kB activation.

Methanol Extracts of Stewartia koreana Inhibit Cyclooxygenase-2 (COX-2) and Inducible Nitric Oxide Synthase (iNOS) Gene Expression by Blocking NF-κB Transactivation in LPS-activated RAW 264.7 Cells

  • Lee, Tae Hoon;Kwak, Han Bok;Kim, Hong-Hee;Lee, Zang Hee;Chung, Dae Kyun;Baek, Nam-In;Kim, Jiyoung
    • Molecules and Cells
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    • v.23 no.3
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    • pp.398-404
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    • 2007
  • Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are involved in various pathophysiological processes such as inflammation and carcinogenesis. In a search for inhibitors of COX-2 and iNOS production we found that extracts of Stewartia koreana strongly inhibited NO and $PGE_2$ production in LPS-treated macrophage RAW 264.7 cells. We have now shown that the mRNA and protein levels of iNOS and COX-2 are reduced by the Stewartia koreana extract (SKE). SKE inhibited expression of an NF-${\kappa}B$ reporter gene in response to LPS, and gel mobility shift assays revealed that SKE reduced NF-${\kappa}B$ DNA-binding activity. The extract also inhibited LPS-induced phosphorylation of $I{\kappa}B-{\alpha}$ and nuclear translocation of p65. Administration of the extract reduced the symptoms of arthritis in a collagen-induced arthritic mouse model. These results indicate that Stewartia extracts contain potentially useful agents for preventing and treating inflammatory diseases.

Korean Red Ginseng suppresses bisphenol A-induced expression of cyclooxygenase-2 and cellular migration of A549 human lung cancer cell through inhibition of reactive oxygen species

  • Song, Heewon;Lee, Yong Yook;Park, Joonwoo;Lee, YoungJoo
    • Journal of Ginseng Research
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    • v.45 no.1
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    • pp.119-125
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    • 2021
  • Background: Korean Red Ginseng (KRG) is a natural product with antiinflammatory and anticarcinogenic effects. We have previously reported that the endocrine-disrupting compound bisphenol A (BPA)-induced cyclooxygenase-2 (COX-2) via nuclear translocation of nuclear factor-kappa B (NF-κB) and activation of mitogen-activated protein kinase and promoted the migration of A549. Here, in this study, we assessed the protective effect of KRG on the BPA-induced reactive oxygen species (ROS) and expression of COX-2 and matrix metalloproteinase-9 (MMP-9) in A549 cells. Methods: The effects of KRG on the upregulation of ROS production and COX-2 and MMP-9 expression by BPA were evaluated by fluorescence-activated cell sorting (FACs) analysis, quantitative reverse transcription polymerase chain reaction, and western blotting. Antimigration ability by KRG was evaluated by migration assay in A549 cells. Results: KRG significantly suppressed the BPA-induced COX-2, the activity of NF-κB, the production of ROS, and the migration of A549 cells. These effects led to the downregulation of the expression of MMP-9. Conclusions: Overall, our results suggest that KRG exerts an antiinflammatory effect on BPA-treated A549 cells via the suppression of ROS and downregulation of NF-κB activation and COX-2 expression which leads to a decrease in cellular migration and MMP-9 expression. These results provide a new possible therapeutic application of KRG to protect BPA-induced possible inflammatory disorders.

A Study of the Antioxidant and Anti-Inflammatory Effects of Dusokohwaeum

  • Yun-Gwon Seon;Jae Min Jeong;Jin-Sol Yoon;Joonyong Noh;Seung Kyu Im;Sung-Pil Bang;Jeong Cheol Shin;Jae-Hong Kim
    • Journal of Acupuncture Research
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    • v.40 no.4
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    • pp.356-367
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    • 2023
  • Background: The aim of this study is to determine the antioxidant and anti-inflammatory effects of Dusokohwaeum (DOE). Methods: To measure the antioxidant and anti-inflammatory effects of DOE, the total flavonoid and polyphenol contents and radical scavenging activity were measured. Furthermore, reactive oxygen species (ROS), nitric oxide, and cytokine production were measured by treating lipopolysaccharide-induced RAW264.7 cells with DOE, and gene expression levels of inducible cyclooxygenase-2, nitric oxide synthase, and cytokines were evaluated. Results: Radical scavenging experiments revealed a significant concentration-dependent increase in scavenging capacity. The production of ROS, nitric oxide, and cytokines in the cells showed a significant concentration-dependent decrease when compared with the control group. The gene expression levels of inducible cyclooxygenase-2, nitric oxide synthase, and cytokines also showed a significant concentration-dependent decrease when compared with the control group. Conclusion: Interestingly, the antioxidant and anti-inflammatory effects of DOE were 23.42 ± 0.64 mg GAE/g and 20.83 ± 0.98 mg QE/g, respectively. The administration of DOE resulted in a concentration-dependent increase in scavenging ability in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging ability experiments. The production of intracellular ROS and nitric oxide was significantly reduced in the presence of DOE. The production of inflammatory cytokines (prostaglandin E2, tumor necrosis factor-alpha [TNF-α], interleukin-1 beta [IL-1β], and IL-6) was significantly reduced in the presence of DOE. Finally, the expression levels of inducible nitric oxide synthase, cyclooxygenase-2, TNF-α, IL-1β, and IL-6 were significantly decreased in the presence of DOE.

Cyclic Expression of Cyclooxygenase-l and -2 in Human Endometrium (인간 자궁내막에서 Cyclooxygenase-1과 -2의 주기적 발현 양상)

  • Park, Dong-Wook;Yang, Hyun-Won;Kwon, Hyuek-Chan;Hwang, Kyung-Joo;Yoo, Jung-Hyun;Lee, Chi-Hyeong;Kim, Sei-Kwang;Cho, Dong-Jea;Oh, Kie-Suk
    • Clinical and Experimental Reproductive Medicine
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    • v.25 no.1
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    • pp.25-33
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    • 1998
  • Cyclooxygenase (COX) is an enzyme involved in the conversion of arachidonic acid to prostaglandins (PGs), and exists in two forms, COX-1 and COX-2. COX has been reported to be involved in early implantation by secretion of PGs which causes permeability of vessels and reaction of decidual cells around the implantation site. Recently, in mice and sheep studies, COX-1 and COX-2 expression in the endometrium has been reported to be different according to implantation and stages of the estrous cycle, but expression of COX-1 and COX-2 in human endometrium during the menstrual cycle has not yet been established. The purpose of this study was to observe the variances of COX-1 and COX-2 expression by immunohistochemical staining in endometrial samples obtained from human hysterectomy specimens and biopsies of women of reproductive age according to different stages of the menstrual cycle. Also, we attempted to observe COX-1 and COX-2 expression in the epithelial and stromal cells of the endometrium obtained during the mid-secretory phase, which were cultured separately. COX-2 showed a cyclic pattern of expression according to the different stages of the menstrual cycle and was strongly expressed particularly at the mid-secretory phase which corresponds to the time of implantation. However, COX-1 tended to be increased in the early proliferative, and mid- and late secretory phases, but was also expressed in the whole menstrual cycle showing no particular pattern. In the separately cultured cells COX-1 was expressed in epithilial cells and COX-2 in the stromal cells. The above results suggest that since COX-2 is expressed at the same time as implantation and cultured cells display a specific secretory pattern, COX-2 has inductive endocrine enzyme properties and has an important effect on endometrial cells during implantation. Also, COX-2 expression in endometrial cells may be utilized as a useful marker of endometrial maturation.

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Protective Mechanism of Bismuth Nitrate Against Gentamicin Nephrotoxicity (질산비스마스의 겐타마이신 신독성 경감기전)

  • Kim, Jung-Sun;Chung, Hae-Young;Rho, Young-Jae;Lee, Sang-Rok
    • YAKHAK HOEJI
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    • v.36 no.6
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    • pp.570-576
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    • 1992
  • The treatment with gentamicin in the presence of pretreatment with bismuth nitrate significantly reduced blood urea nitrogen compared with given gentamicin alone. But the amelioration of gentamicin-induced nephrotoxicity by bismuth nitrate was abolished by pretreatment with indomethacin that is cyclooxygenase inhibitor, which significantly decreased renal glutathione S-transferase activity and thiobarbituric acid reactive substance compared with mice of given gentamicin and bismuth nitrate. On the other hand, treatment with bismuth nitrate significantly increased prostaglandin $E_2$ production in rat kidney slice. These results suggest that bismuth nitrate might ameliorate the nephrotoxicity of gentamicin via prostaglandin $E_2$ production.

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Inhibitory Effects of Complex of Mulberry Extract on Degenerative Arthritis (상심자추출물 등 복합물의 퇴행성관절염 억제효과)

  • Seo, Hyeong Ho;Jeong, Jong Moon
    • Korean Journal of Medicinal Crop Science
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    • v.22 no.4
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    • pp.262-269
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    • 2014
  • Complex of mulberry extract (CME) is composed of extracts of mulberry (Morus alba L.) fruit, mulberry leaves and black beans (Glycine max (L.) Merr.). In this study, we investigated prevention effects of CME on degenerative arthritis. The $SC_{50}$ value of DPPH radical scavenging by CME was $158.49{\pm}11.35{\mu}/mL$. We found that CME significantly reduced the production of nitric oxide (NO) and protein expression of cyclooxygenase-2 (COX-2) in RAW 264.7 cells which were activated by LPS. Experiments using animal model of degenerative arthritis showed that CME (400 mg/kg body weight) inhibited the production of TNF-${\alpha}$ (77.5%) and IL-$1{\beta}$ (95.0%). Furthermore, it was observed that CME reduced to 85.9% of paw edema induced by carrageenan. These results suggest that CME could improve degenerative arthritis.

Cyclooxgenase Inhibitory Components from Portulaca oleracea

  • Kim, Jeong-Ah;Yang, Seo-Young;Kang, Sang-Jin;Kim, Young-Ho
    • Natural Product Sciences
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    • v.18 no.1
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    • pp.22-25
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    • 2012
  • Five triterpenoids, epifriedelanol (1), friedelin (2), lupeol (3), ${\beta}$-sitosterol (4), daucosterol (5), and one phenyl propanoids ester, trans-docosanoyl ferulate (6) were isolated from the whole parts of Portulaca oleracea. They were determined using a combination of spectroscopic analyses ($^1H-$, $^{13}C$-NMR, and MS data) and evaluated for their cyclooxygenase inhibitory activity. Compound 6 exhibited inhibitory effect with $IC_{50}$ values of $40.2{\mu}M$ and 1.6 mM on COX-1 and COX-2 activities, respectively.