• Title/Summary/Keyword: COX-1, COX-2

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The Experimental Study on Anti-inflammatory Effects of Eungapbang (EGB) (은갑방(銀甲方)이 염증 관련 cytokines의 유전자 발현과 생성량에 미치는 영향)

  • Lee, Bo-Ra;Yoo, Dong-Youl
    • The Journal of Korean Obstetrics and Gynecology
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    • v.22 no.3
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    • pp.83-98
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    • 2009
  • Purpose: This study was performed to evaluate the anti-inflammatory effect of Eungapbang extract (EGB). Methods: To evaluate the anti-inflammatory effects of EGB, we nourished RAW 264.7 cell lines in the laboratory dish. Next, inflammatory cytokine concentrations were analyzed. Then, sera were prepared from blood after lipopolysaccharide (LPS) injection in chemically induced mouse models of intestinal inflammation, and Interleukin-1${\beta}$ (IL-1${\beta}$), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-${\alpha}$) were measured using ELISA kits. Results: 1. EGB significantly suppressed the expression levels of IL-1${\beta}$ and NOS-II genes at 100, 50 and 10 ${\mu}g/m{\ell}$ concentrations, and IL-6, TNF-${\alpha}$ and COX-2 mRNAs at 100 and 50 ${\mu}g/m{\ell}$ concentrations. 2. EGB significantly reduced the production level of IL-1${\beta}$ and TNF-${\alpha}$ at 100${\mu}g/m{\ell}$ concentrations, and IL-6 at 100 and 50 ${\mu}g/m{\ell}$ concentrations. 3. EGB significantly decreased the production level of IL-1${\beta}$ and IL-6 in sera of acute inflammation induced mice. 4. EGB could suppress the expression level of IL-1${\beta}$ and IL-6 mRNA in spleen tissues in acute inflammation induced mice. Conclusion: On the basis of the above results, it is confirmed that the anti-inflammatory effects of EGB were recognized. Therefore, EGB is recommended as promising therapy for treatment of such ailments as pelvic inflammatory disease.

Association Between Plasma Homocysteine Level and Mortality: A Mendelian Randomization Study

  • Chang Kyun Choi ;Sun-Seog Kweon;Young-Hoon Lee;Hae-Sung Nam;Seong-Woo Choi;Hye-Yeon Kim;Min-Ho Shin
    • Korean Circulation Journal
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    • v.53 no.10
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    • pp.710-719
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    • 2023
  • Background and Objectives: In previous studies, high homocysteine levels were associated with high cardiovascular mortality. However, these results were inconsistent with those of randomized controlled trials. We aimed to evaluate the causal role of homocysteine on allcause and cardiovascular mortality using Mendelian randomization (MR) analysis. Methods: This study included the 10,005 participants in the Namwon Study. In conventional observational analysis, age, sex, survey years, lifestyles, body mass index, comorbidities, and serum folate level were adjusted using multivariate Cox proportional regression. MR using 2-stage least squares regression was used to evaluate the association between genetically predicted plasma homocysteine levels and mortality. Age, sex, and survey years were adjusted for each stage. The methylenetetrahydrofolate reductase (MTHFR) polymorphism was used as an instrumental variable for predicting plasma homocysteine levels. Results: Observed homocysteine levels were positively associated with all-cause (hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.26-1.54) and cardiovascular (HR, 1.62; 95% CI, 1.28-2.06) mortality when plasma homocysteine levels doubled. However, these associations were not significant in MR analysis. The HRs of doubling genetically predicted plasma homocysteine levels for all-cause and cardiovascular mortality were 0.99 (95% CI, 0.62-1.57) and 1.76 (95% CI, 0.54-5.77), respectively. Conclusions: This MR analysis did not support a causal role for elevated plasma homocysteine concentrations in premature deaths.

Inhibitory Effect of Ginkgolide B on Platelet Aggregation in a cAMP- and cGMP-dependent Manner by Activated MMP-9

  • Cho, Hyun-Jeong;Nam, Kyung-Soo
    • BMB Reports
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    • v.40 no.5
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    • pp.678-683
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    • 2007
  • Extracts from the leaves of the Ginkgo biloba are becoming increasingly popular as a treatment that is claimed to reduce atherosclerosis, coronary artery disease, and thrombosis. In this study, the effect of ginkgolide B (GB) from Ginkgo biloba leaves in collagen (10 ${\mu}g/ml$)-stimulated platelet aggregation was investigated. It has been known that human platelets release matrix metallo-proteinase-9 (MMP-9), and that it significantly inhibited platelet aggregation stimulated by collagen. Zymographic analysis confirmed that pro-MMP-9 (92-kDa) was activated by GB to form an MMP-9 (86-kDa) on gelatinolytic activities. And then, activated MMP-9 by GB dose-dependently inhibited platelet aggregation, intracellular $Ca^{2+}$ mobilization, and thromboxane $A_2$ ($TXA_2$) formation in collagen-stimulated platelets. Activated MMP-9 by GB directly affects down-regulations of cyclooxygenase-1 (COX-1) or $TXA_2$ synthase in a cell free system. In addition, activated MMP-9 significantly increased the formation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which have the anti-platelet function in resting and collagen-stimulated platelets. Therefore, we suggest that activated MMP-9 by GB may increase the intracellular cAMP and cGMP production, inhibit the intracellular $Ca^{2+}$ mobilization and $TXA_2$ production, thereby leading to inhibition of platelet aggregation. These results strongly indicate that activated MMP-9 is a potent inhibitor of collagen-stimulated platelet aggregation. It may act a crucial role as a negative regulator during platelet activation.

The Association of Hospital Volume of Percutaneous Coronary Intervention with Cardiac Mortality

  • Kim, Jae-Hyun;Kim, Jang-Mook;Park, Eun-Cheol
    • Health Policy and Management
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    • v.28 no.2
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    • pp.168-177
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    • 2018
  • Background: This study investigates the potential volume and outcome association of coronary heart disease (CHD) patients who have undergone percutaneous coronary intervention (PCI) using a large and representative sample. Methods: We used a National Health Insurance Service-Cohort Sample Database from 2002 to 2013 released by the Korean National Health Insurance Service. A total of 8,908 subjects were analyzed. The primary analysis was based on Cox proportional hazards models to examine our hypothesis. Results: After adjusting for confounders, the hazard ratio of thirty-day and 1-year mortality in hospitals with a low volume of CHD patients with PCI was 2.8 and 2.2 times higher (p=0.00) compared to hospitals with a high volume of CHD patients with PCI, respectively. Thirty-day and 1-year mortality of CHD patients with PCI in low-volume hospitals admitted through the emergency room were 3.101 (p=0.00) and 2.8 times higher (p=0.01) than those in high-volume hospitals, respectively. Only 30-day mortality in low-volume hospitals of angina pectoris and myocardial infarction patients with PCI was 5.3 and 2.4 times those in high-volume hospitals with PCI, respectively. Conclusion: Mortality was significantly lower when PCI was performed in a high-volume hospital than in a low-volume hospital. Among patients admitted through the emergency room and diagnosed with angina pectoris, total PCI volume (low vs. high) was associated with significantly greater cardiac mortality risk of CHD patients. Thus, There is a need for better strategic approaches from both clinical and health policy standpoints for treatment of CHD patients.

Gintonin regulates inflammation in human IL-1β-stimulated fibroblast-like synoviocytes and carrageenan/kaolin-induced arthritis in rats through LPAR2

  • Kim, Mijin;Sur, Bongjun;Villa, Thea;Yun, Jaesuk;Nah, Seung Yeol;Oh, Seikwan
    • Journal of Ginseng Research
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    • v.45 no.5
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    • pp.575-582
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    • 2021
  • Background: In ginseng, there exists a glycolipoprotein complex with a special form of lipid LPAs called Gintonin. The purpose of this study is to show that Gintonin has a therapeutic effect on rheumatoid arthritis through LPA2 receptors. Methods: Fibroblast-like synoviocytes (FLS) were treated with Gintonin and stimulated with interleukin (IL)-1β. The antioxidant effect of Gintonin was measured using MitoSOX and H2DCFDA experiments. The anti-arthritic efficacy of Gintonin was examined by analyzing the expression levels of inflammatory mediators, phosphorylation of mitogen-activated protein kinase (MAPK) pathways, and translocation of nuclear factor kappa B (NF-κB)/p65 into the nucleus through western blot. Next, after treatment with LPAR2 antagonist, western blot analysis was performed to measure inflammatory mediator expression levels, and NF-κB signaling pathway. Carrageenan/kaolin-induced arthritis rat model was used. Rats were orally administered with Gintonin (25, 50, and 100 mg/kg) every day for 6 days. The knee joint thickness, squeaking score, and weight distribution ratio (WDR) were measured as the behavioral parameters. After sacrifice, H&E staining was performed for histological analysis. Results: Gintonin significantly inhibited the expression of iNOS, TNF-α, IL-6 and COX-2. Gintonin prevented NF-κB/p65 from moving into the nucleus through the JNK and ERK MAPK phosphorylation in FLS cells. However, pretreatment with an LPA2 antagonist significantly reversed these effects of Gintonin. In the arthritis rat model, Gintonin suppressed all parameters that were measured. Conclusion: This study suggests that LPA2 receptor plays a key role in mediating the anti-arthritic effects of Gintonin by modulating inflammatory mediators, the MAPK and NF-κB signaling pathways.

A Newly Synthesized Flavone from Luteolin Escapes from COMT-Catalyzed Methylation and Inhibits Lipopolysaccharide-Induced Inflammation in RAW264.7 Macrophages via JNK, p38 and NF-κB Signaling Pathways

  • Ye, Lin;Xin, Yang;Wu, Zhi-yuan;Sun, Hai-jian;Huang, De-jian;Sun, Zhi-qin
    • Journal of Microbiology and Biotechnology
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    • v.32 no.1
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    • pp.15-26
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    • 2022
  • Luteolin is a common dietary flavone possessing potent anti-inflammatory activities. However, when administrated in vivo, luteolin becomes methylated by catechol-O-methyltransferases (COMT) owing to the catechol ring in the chemical structure, which largely diminishes its anti-inflammatory effect. In this study, we made a modification on luteolin, named LUA, which was generated by the chemical reaction between luteolin and 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH). Without a catechol ring in the chemical structure, this new flavone could escape from the COMT-catalyzed methylation, thus affording the potential to exert its functions in the original form when administrated in the organism. Moreover, an LPS-stimulated RAW cell model was applied to detect the anti-inflammatory properties. LUA showed much more superior inhibitory effect on LPS-induced production of NO than diosmetin (a major methylated form of luteolin) and significantly suppressed upregulation of iNOS and COX-2 in macrophages. LUA treatment dramatically reduced LPS-stimulated reactive oxygen species (ROS) and mRNA levels of pro-inflammatory mediators such as IL-1β, IL-6, IL-8 and IFN-β. Furthermore, LUA significantly reduced the phosphorylation of JNK and p38 without affecting that of ERK. LUA also inhibited the activation of NF-κB through suppression of p65 phosphorylation and nuclear translocation.

Orostachydis Herba and Fermented Orostachydis Herba Enhances Anti-Inflammatory and Anti-oxidant Effect against Lipopolysaccharide-Induced Acute Liver Injury in Mice (Lipopolysaccharide로 유발한 급성 간손상 마우스 모델에서 와송과 발효 와송의 항산화 조절과 염증 예방 효과 비교 연구)

  • Kang, HanEun;Lee, AhReum;Roh, Seong-Soo;Seo, Young-Bae
    • The Korea Journal of Herbology
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    • v.32 no.2
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    • pp.65-75
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    • 2017
  • Objectives : This study aimed to evaluate the protective effect of Orostachydis Herba (OH) and Fermented OH (OHF) against the acute liver injury by lipopolysaccharide (LPS). Methods : OHF by 4 lactic bacteria such as (Lactobacillus hilgardii (OHF1), Leuconostoc mesenteroides (OHF2), Pediococcus acidilactici (OHF3), Saccharomyces cerevisiae (OHF4)) were prepared. Samples were selected to OHF0, OHF2, OHF3 based on UPLC analysis, DPPH, ABTS radical scavenging activities. To evaluate the protective effect of OHF on liver injury mice, ICR mice were divided into 5 groups: Normal mice (Nor), LPS (20 mg/kg) treated mice (Veh), administrated OHF0, OHF2 OHF3 200 mg/kg body weight during 8 days before LPS injection. Serum and liver were collected 24 hours after LPS injection. Results : The activity was high in order of OHF0 and OHF3 in DPPH and ABTS radical scavenging activities. The quercetin contents for bioactive ingredient of OH was 5.39, kaempferol contents was 9.94 by UPLC analysis. The LPS-treated vehicle group significantly increased liver weight, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in serum. In contrast, administrated OHF3 group decreased liver weight, AST, ALT. In addition, OHF3 groups reduced the elevated levels of reactive oxygen species (ROS) in serum and tissues. Moreover, AP-1, iNOS and COX-2 were significantly decreased in OHF2 and OHF3. But $NF-{\kappa}B$ p65 and $TNF-{\alpha}$ only showed a significant reduction in OHF3. Conclusions : Therefore, these results suggest that fermented Orostachydis Herba might be protective effect on liver injury through anti-oxidant effect.

Synergistic Effects of Exemestane and Aspirin on MCF-7 Human Breast Cancer Cells

  • Hu, Li-Xia;Du, Ying-Ying;Zhang, Ying;Pan, Yue-Yin
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5903-5908
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    • 2012
  • Objective: The purpose of this study is to investigate the combined effects of exemestane and aspirin on MCF-7 human breast cancer cells. Methods: Antiproliferative effects of exemestane and aspirin, alone and in combination, on growth of MCF-7 human breast cancer cells were assessed using the MTT assay. Synergistic interaction between the two drugs was evaluated in vitro using the combination index (CI) method. The cell cycle distribution was analyzed by flow cytometry and Western blotting was used to investigate the expression of cyclooxygenase-1, cyclooxygenase-2 and Bcl-2. Results: MTT assays indicated that combination treatment obviously decreased the viability of MCF-7 human breast cancer cells compared to individual drug treatment (CI<1). In addition, the combination of exemestane and aspirin exhibited a synergistic inhibition of cell proliferation, significantly arrested the cell cycle in the $G_0/G_1$ phase and produced a stronger inhibitory effect on COX-1 and Bcl-2 expression than control or individual drug treatment. Conclusion: These results indicate that the combination of exemestane and aspirin might become a useful method to the treatment of hormone-dependent breast cancer. The combination of the two inhibitors significantly increased the response as compared to single agent treatment, suggesting that combination treatment could become a highly effective approach for breast cancer.

Relation between the Total Diet Quality based on Korean Healthy Eating Index and the Incidence of Metabolic Syndrome Constituents and Metabolic Syndrome among a Prospective Cohort of Korean Adults (한국 성인의 식생활평가지수에 기반한 전체 식사의 질과 대사증후군 구성요소 및 대사증후군 발생의 연관성)

  • Shin, Saerom;Lee, Seungmin
    • Korean Journal of Community Nutrition
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    • v.25 no.1
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    • pp.61-70
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    • 2020
  • Objectives: This study examined the association of the total diet quality with the incidence risk of metabolic syndrome constituents and metabolic syndrome among Korean adults. Methods: Based on a community-based cohort of the Korean Genome and Epidemiology Study (KoGES) from 2001 to 2014, data from a total of 5,549 subjects (2,805 men & 2,744 women) aged 40~69 years at the baseline with a total follow-up period of 38,166 person-years were analyzed. The criteria of the National Cholesterol Education Program Adult Treatment Panel was employed to define metabolic syndrome. The total diet quality was estimated using the Korean Healthy Eating Index (KHEI). Hazard ratios (HR) and 95% confidence intervals (CI) for risk of metabolic syndrome constituents and metabolic syndrome in relation to KHEI quintile groups was calculated by multivariate Cox proportional hazards regression model. Results: After adjusting for age, energy intake, income, education, physical activity, smoking, and drinking, the incidence of abdominal obesity and high blood pressure was significantly lower, by approximately 29.7% (P < 0.01) and 25.2% (P < 0.01), respectively, in the fifth KHEI quintile compared to the first quintile in men. A significant decreasing trend of the metabolic syndrome incidence was observed across the improving levels of KHEI (HRq5vs.q1: 0.775, 95% CIq5vs.q1: 0.619~0.971, P for trend < 0.01). In women, the incidence of abdominal obesity and metabolic syndrome was significantly lower, by approximately 29.8% (P < 0.01) and 22.5% (P < 0.05), respectively, in the fifth KHEI quintile compared to the first quintile adjusting for multiple covariates. On the other hand, the linear trend of metabolic syndrome risk across the KHEI levels did not reach the significance level. Conclusions: A better diet quality can prevent future metabolic syndrome and its certain risk factors among Korean men and women.

Ethyl Acetate Fraction of Cnidium monnieri(L). Cussion Suppresses PAM plus A23187-induced Inflammation Reaction through Blockade of NF-κB and MAPK activation (벌사상자 Ethyl Acetate 분획물의 항염증활성연구)

  • Kang, Ok-Hwa;Kim, Sang-Young;Kwon, Dong-Yeul
    • Korean Journal of Pharmacognosy
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    • v.46 no.3
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    • pp.195-202
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    • 2015
  • Cnidium monnieri (L). Cussion is used as a tonic agent in traditional oriental medicine. However, the molecular mechanism of mast cell-mediated anti-inflammatory modulation has not been fully understood. The aim of the present study was to demonstrate the effects of Cnidium monnieri (L). Cussion eathyl acetate fraction on the expression of pro-inflammatory cytokines, as well as to elucidate its mechanism of action in the human mast cell line (HMC-1). Cells were stimulated with phorbol 12-myristate 13-acetate (PMA) plus A23187 in the presence or absence of Cnidium monnieri (L). Cussion eathyl acetate fraction. Cnidium monnieri (L). Cussion eathyl acetate fraction significantly inhibited the PMA plus A23187-induction of inflammatory cytokines such as tumor necrosis factor (TNF)-$\alpha$, interleukin (IL)-6 and IL-8. Moreover, EtOAc fraction attenuated cyclooxygenase (COX)-2 expression. In activated HMC-1 cells, phosphorylation of extra-signal response kinase (ERK) 1/2 decreased after treatment with EtOAc fraction. Moreover EtOAc fraction inhibited PMA plus A23187-induced nuclear factor (NF)-${\kappa}B$ activation, $I{\kappa}B$ degradation. EtOAc fraction suppressed the expression of TNF-$\alpha$, IL-6, IL-8 through a decrease in the ERK 1/2, as well as activation of NF-${\kappa}B$. These results indicated that Cnidium monnieri (L). Cussion EtOAc fraction exerted a regulatory effect on inflammatory reactions mediated by mast cells.