• Title/Summary/Keyword: COX-1 activity

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Anti-inflammatory effects of Ishige sinicola ethanol extract in LPS-induced RAW 264.7 cell and mouse model (LPS로 유도된 RAW 264.7 Cell과 마우스 모델에 대한 넓패(Ishige sinicola) 에탄올 추출물의 항염증 효과)

  • Kim, Ji-Hye;Kim, Min-Ji;Kim, Koth-Bong-Woo-Ri;Park, Sun-Hee;Cho, Kwang-Su;Kim, Go-Eun;XU, Xiaotong;Lee, Da-Hye;Park, Ga-Ryeong;Ahn, Dong-Hyun
    • Food Science and Preservation
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    • v.24 no.8
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    • pp.1149-1157
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    • 2017
  • Inflammation is the first response of the immune system to infection or irritation in our body. The use of medicinal plants has been widely applied as an alternative source for drug development. One of marine natural resources, the anti-inflammatory effect of Ishige sinicola ethanol extract (ISEE), was evaluated by using LPS-induced RAW 264.7 cell and mice model. As a result, the production of nitric oxide (NO) and pro-inflammatory cytokines (IL-6, IL-$1{\beta}$, TNF-${\alpha}$) were inhibited with increasing concentration of ISEE without any cytotoxicity. Furthermore, ISEE suppressed the expression of not only inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-${\kappa}B$) p65, and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK) in a dose-dependent manner. In mice ear edema test, the formation of edema was reduced at the highest dosage of ISEE and the reduction of the number of infiltrated mast cells was observed in histological analysis. These results indicate that ISEE has a potent anti-inflammatory activity and can be used as a pharmaceutical material for many kinds of inflammatory disease.

Diabetes Mellitus and Risk of Colorectal Cancer Mortality in Japan: the Japan Collaborative Cohort Study

  • Tan, Ce;Mori, Mitsuru;Adachi, Yasushi;Wakai, Kenji;Suzuki, Sadao;Suzuki, Koji;Hashimoto, Shuji;Watanabe, Yoshiyuki;Tamakoshi, Akiko
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.10
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    • pp.4681-4688
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    • 2016
  • Objective: Our aim was to estimate whether diabetes mellitus (DM) may be associated with an increased risk of colorectal cancer (CRC) mortality in Japan. Methods: The Japan Collaborative Cohort (JACC) Study is a nationwide prospective study, initiated in 1988, which involves 110,585 subjects (age range: from 40 to 79 years; 46,395 males and 64,190 females). Our present analysis population comprised 96,081 (40,510 men and 55,571 women) who provided details on DM history. The questionnaire also included age, sex, weight, height, family history of CRC, smoking, drinking and exercise habits, and education. Cox proportional-hazard regression was used to estimate the hazard ratio (HR). We used SPSS 21 software to analyze all data. Results: Among the participants with DM, we followed up for 71,174 person-years and 640. deaths from CRC were confirmed; and, among the non-diabetic participants, 785 CRC deaths were identified during 1,499,324 person-years. After adjusting for multivariate confounding factors, such as age, sex, body mass index (BMI), family history of colorectal cancer, smoking habit, drinking habit, physical activity (sports and walking) and education, DM was associated with an increased risk of CRC death (HR 1.4, 95% confidence interval [CI] 1.0-2.0). Diabetic women, but not diabetic men, experienced increased mortality from CRC (HR 1.7, 95% CI 1.0-3.0). Conclusion: The risk of CRC mortality is significantly increased in both sexes and women with diabetes, but no significant increase was seen for diabetic men among Japanese.

Anti-inflammatory Activities of Taxifolin from Opuntia humifusa in Lipopolysaccharide Stimulated RAW 264.7 Murine Macrophages (천년초의 Taxifolin이 마우스대식세포(RAW 264.7 cell)에 미치는 항염증활성)

  • Kim, Jaeyoung;Lee, Yonghwa;An, Hyeon-jin;Lee, Jae-duk;Yi, Yongsub
    • Journal of Applied Biological Chemistry
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    • v.58 no.3
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    • pp.241-246
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    • 2015
  • This study was performed to investigate the antiinflammatory activities of taxifolin from Opuntia humifusa. A potent anti-oxidant activity was shown from the leaf extract at $IC_{50}$ value of $38.33{\pm}1.07{\mu}g/mL$ and fruit extract at $IC_{50}$ value of $40.23{\pm}2.21{\mu}g/mL$ by 1,1-diphenyl-2-picrylhydrazyl assay. Fraction of taxifolin from leaf extract identified using high performance liquid chromatography and gas chromatography/mass spectrometry. The results of cell viability indicated that taxifolin did not show cytotoxicity on RAW 264.7 cells at $500{\mu}M$ of concentration. The result showed that taxifolin inhibited lipopolysaccharide (LPS)-induced production of Nitrite oxide. In addition, taxifolin inhibited LPS-induced tumor necrosis factor-${\alpha}$ and interleukin-6 production by cytokine assay and cyclooxygenase-2 expression by western blot analysis, meaning taxifolin has a significant anti-inflammatory effect. Our results suggested that taxifolin from Opuntia humifusa showed anti-inflammatory activities.

Improvement Effect of Sprout of Coix lacryma-jobi var. mayuen Stapf Water Extract on DSS-Induced Ulcerative Colitis in Mice. (DSS로 궤양성 대장염 유발된 동물모델에서 의이아(薏苡芽) 열수 추출물의 개선 효과)

  • Kim, Min Ju;Shin, Mi-Rae;Lee, Jin A;Park, Soon-Ae;Park, Hae-Jin;Lee, Jeong Hoon;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.35 no.6
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    • pp.21-28
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    • 2020
  • Objectives : The objective of this study was to investigate the improvement effect of Sprout of Coix lacryma-jobi var. mayuen Stapf water extract (SC) on the dextran sulfate sodium (DSS)-induced ulcerative colitis mice. Methods : The antioxidant activity of SC was measured through total polyphenol and total flavonoid content in vitro. The experiment was conducted with seven-week-old male Balb/c mice. After 1 week adaptation, acute colitis was induced by oral administration of 5% DSS dissolved in drinking water, for 7 days. And normal mice received drinking water without DSS throughout the entire experimental period. For each experiment, the mice were divided into 4 groups and 24 colitis mice were arbitrarily allocated into 3 groups (n = 8/group); Normal group, Control group, SC 100 mg/kg treated group (SCL), SC 200 mg/kg treated group (SCH). Serum and colon tissues were collected after one weeks of drug administration. Results : ROS levels, ONOO- levels, AST, and ALT in serum were decreased in SC treated groups compared to the control group. Western blotting measurements of Nrf2, HO-1, SOD, catalase, GPx-1/2, IL-4, IL-10, and Bcl2 showed that the SC treated groups was increased compared to the Control group. Also, western blot measurements of NF-κBp65, p-IκBα, COX-2, iNOS, TNF-α, IL-1β, Bax, and Caspase-3 showed that the SC treated groups was reduced compared to the Control group. Conclusion : Taken together, these results suggest that SC treatment can attenuate the DSS-induced colitis though inhibiting NF-κB pathway and enhancing Nrf2 pathway. Therefore, SC was the potential to be used as a natural therapeutic drug.

The protective effect of Areca Semen and Toosendan Fructus mixture in a chronic model of reflux esophagitis (빈랑자와 천련자 복합물의 만성 역류성 식도염에서 보호 효과)

  • Shin, Mi-Rae;Lee, Jin A;Kim, Min Ju;An, Hyo-Jin;Roh, Seong-Soo
    • The Korea Journal of Herbology
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    • v.35 no.1
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    • pp.57-68
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    • 2020
  • Objective : The aim of present study was to clarify the effect of Areca Semen and Toosendan Fructus Mixture (AT-mix) on chronic reflux esophagitis (CRE) in rats. Methods : The antioxidant activity of AT-mix was measured through DPPH and ABTS radical scavenging activities in vitro. CRE was induced in SD rats (5 weeks, male) by ligating the border forestomach and granular portion with 2-0 silk and the duodenum near the pyloric portion was covered with 2-mm wide piece of 18-Fr Nélaton catheter. And then rats were treated AT-mix 200 mg/kg one daily for 14 days. The anti-oxidant and inflammatory protein levels were evaluated using western blotting. Results : Gross lesion of esophageal mucosa after AT-mix treatment showed a superior enhancement compared with that of CRE control rats. AT-mix treatment strongly reduced both DPPH and ABTS radical scavenging activities (DPPH, IC50 8.15±0.14 ㎍/mL; ABTS, IC50 24.69±0.03 ㎍/mL, repspectively). Levels of the NADPH oxidase subunit including NOX4 and p22phox increased in CRE control rats. Otherwise, AT-mix treatment significantly reduced. The activation of Nuclear factor-erythroid 2-related factor 2 (Nrf2) led to significantly the up-regulation of HO-1. The inhibition of IκBα phosphorylation led to NF-κB inactivation. Subsequently, NF-κB inactivation significantly induced the decrease of COX-2, iNOS, TNF-α, and IL-6 protein expressions. Conclusion : Taken together, these results suggest that AT-mix treatment can attenuate the esophageal mucosal ulcer though inhibiting NF-κB pathway and enhancing Nrf2/HO-1 pathway. Thus, the additional mechanism study about AT-mix would need for the development as a safe herbal therapy for CRE.

Ficus vasculosa Wall. ex Miq. Inhibits the LPS-Induced Inflammation in RAW264.7 Macrophages

  • Ji-Won, Park;Jin-Mi, Park;Sangmi, Eum;Jung Hee, Kim;Jae Hoon, Oh;Jinseon, Choi;Tran The, Bach;Nguyen, Van Sinh;Sangho, Choi;Kyung-Seop, Ahn;Jae-Won, Lee
    • Microbiology and Biotechnology Letters
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    • v.50 no.4
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    • pp.574-583
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    • 2022
  • Ficus vasculosa Wall. ex Miq. (FV) has been used as a herbal medicine in Southeast Asia and its antioxidant activity has been shown in previous studies. However, it has not yet been elucidated whether FV exerts anti-inflammatory effects on activated-macrophages. Thus, we aimed to evaluate the ameliorative property of FV methanol extract (FM) on lipopolysaccharide (LPS)-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 macrophages. The experimental results indicated that FM decreased the production of inflammatory mediators (NO/PGE2) and the mRNA/protein expression of iNOS and COX-2 in LPS-stimulated RAW264.7 cells. FM also reduced the secretion of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein (MCP)-1 in LPS-stimulated RAW264.7 cells. Results also demonstrated that FM improved inflammatory response in LPS-stimulated A549 airway epithelial cells by inhibiting the production of cytokines, such as IL-1β, IL-6 and TNF-α. In addition, FM suppressed MAPK activation and NF-κB nuclear translocation induced by LPS. FM also upregulated the mRNA/protein expression levels of heme oxygenase-1 and the nuclear translocation of nuclear factor erythroid 2-related factor 2 in RAW264.7 cells. In an experimental animal model of LPS-induced acute lung injury, the increased levels of molecules in bronchoalveolar lavage (BAL) fluid were suppressed by FM administration. Collectively, it was founded that FM has anti-inflammatory properties on activated-macrophages by suppressing inflammatory molecules and regulating the activation of MAPK/NF-κB signaling.

Prognostic Value of Fibroblastic Foci in Patients with Usual Interstitial Pneumonia (통상성 간질성 폐렴 환자 예후인자로서의 섬유모세포병소(fibroblastic foci)의 유용성)

  • Park, Yong-Bum;Kang, Gil-Hyun;Shim, Mae-Sun;Lim, Chae-Man;Lee, Sang-Do;Koh, Youn-Suck;Kim, Woo-Sung;Kim, Won-Dong;Kitaichi, Masanori;Kim, Dong-Soon
    • Tuberculosis and Respiratory Diseases
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    • v.53 no.3
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    • pp.309-318
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    • 2002
  • Background : Usual interstitial pneumonia (UIP) is a fatal progressive fibrotic disorder of the lung with unknown etiology and characterized by a poor response to conventional immunosuppressive therapy. The histologic hallmark of UIP is parchy distribution of subpleural fibrosis and fibroblastic foci(FBF) with interposed normal appearing lung. Because FBF is a collection of actively proliferating myofibroblasts, it can be a marker of activity and prognosis of UIP. However, there were contradictory reports about the correlation between the degree of FBF and survival. Therefore we performed this study to investigate the value of FBF as prognostic marker of UIP. Methods : This was a retrospective study on the 46 patients(M:F=33:13, mean age:$59{\pm}12$ years) with UIP diagnosed by the surgical lung biopsy at the Asan Medical Center, Seoul, Korea between 1990 and 2000 and had follow-up of more than a year. All the biopsy specimens were reevaluated and diagnosed as UIP according to the ATS/ERS classification. Semiquantitative grading of FBF(absent, 0; mild 1; moderate 2; marked 3) by the experienced pathologists who did not know the clinical findings were compared to the clinical data and the follow up course. Results : Thirteen patients(28.2%) died of UIP progression during the study period. The median survival time of all the subjects was 26 months after the biopsy. At the univariate analysis, FVC, $D_Lco$, smoking history and the grade of FBF were significantly related to the survial. The survival was longer in subjects with lesser degrees of FBF, higher DLco, higher FVC and history of smoking. However the multivariate analysis with Cox regression test showed the extent of FBF was the only independent prognostic marker of UIP. Conclusion : These data suggested that the extent of FBF on the surgical lung biopsy can be used as a prognostic marker of UIP.

Weight Gain and Alcohol Drinking Associations with Breast Cancer Risk in Japanese Postmenopausal Women - Results from the Japan Collaborative Cohort (JACC) Study

  • Nitta, Junichi;Nojima, Masanori;Ohnishi, Hirofumi;Mori, Mitsuru;Wakai, Kenji;Suzuki, Sadao;Fujino, Yoshihisa;Lin, Yingsong;Tamakoshi, Koji;Tamakoshi, Akiko
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1437-1443
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    • 2016
  • Background: We investigated four factors, height, weight gain since age 20, physical activity, and alcohol drinking, for associations with risk of breast cancer (BC) according to menopausal status, using the latest data of the Japan Collaborative Cohort Study (JACC Study). Materials and Methods: We confined the analysis to 24 areas available of cancer incidence information, excluding women with a previous diagnosis of BC. Baseline data were collected from 38,610 (9,367 premenopausal, and 29,243 postmenopausal) women during 1988 and 1990. The study subjects were followed-up at the end of 2009, and 273 (84 premenopausal, and 189 postmenopausal) cases of BC were newly diagnosed in 501,907 person-years. The Cox model was used to estimate a hazards ratio (HR) and its 95% confidence interval (CI) of BC risk. Results: As a result of the multivariate analysis adjusting for age at baseline survey, age at menarche, number of live births, and, age at first delivery, weight gain since age 20 of 6.7 kg-9.9 kg, and ${\geq}10.0kg$ were significantly associated with increased risk for postmenopausal BC (HR=2.48, 95% CI 1.40-4.41, and, HR=2.94, 95% CI 1.84-4.70, respectively). Significantly increased trend of BC risk was also observed in weight gain since age 20 (p for trend, p<0.001). Amount of ethanol intake per day${\geq}15.0g$ was significantly associated with increased risk for postmenopausal BC in the multivariable-adjusted analysis (HR=2.74, 95% CI 1.32-5.70). Conclusions: Higher weight gain in adulthood and larger amounts of ethanol intake were significantly associated with increased risk of BC in Japanese postmenopausal women. None of the investigated factors were significantly associated with BC risk in Japanese premenopausal women.

Prognostic Evaluation of Categorical Platelet-based Indices Using Clustering Methods Based on the Monte Carlo Comparison for Hepatocellular Carcinoma

  • Guo, Pi;Shen, Shun-Li;Zhang, Qin;Zeng, Fang-Fang;Zhang, Wang-Jian;Hu, Xiao-Min;Zhang, Ding-Mei;Peng, Bao-Gang;Hao, Yuan-Tao
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.14
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    • pp.5721-5727
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    • 2014
  • Objectives: To evaluate the performance of clustering methods used in the prognostic assessment of categorical clinical data for hepatocellular carcinoma (HCC) patients in China, and establish a predictable prognostic nomogram for clinical decisions. Materials and Methods: A total of 332 newly diagnosed HCC patients treated with hepatic resection during 2006-2009 were enrolled. Patients were regularly followed up at outpatient clinics. Clustering methods including the Average linkage, k-modes, fuzzy k-modes, PAM, CLARA, protocluster, and ROCK were compared by Monte Carlo simulation, and the optimal method was applied to investigate the clustering pattern of the indices including platelet count, platelet/lymphocyte ratio (PLR) and serum aspartate aminotransferase activity/platelet count ratio index (APRI). Then the clustering variable, age group, tumor size, number of tumor and vascular invasion were studied in a multivariable Cox regression model. A prognostic nomogram was constructed for clinical decisions. Results: The ROCK was best in both the overlapping and non-overlapping cases performed to assess the prognostic value of platelet-based indices. Patients with categorical platelet-based indices significantly split across two clusters, and those with high values, had a high risk of HCC recurrence (hazard ratio [HR] 1.42, 95% CI 1.09-1.86; p<0.01). Tumor size, number of tumor and blood vessel invasion were also associated with high risk of HCC recurrence (all p< 0.01). The nomogram well predicted HCC patient survival at 3 and 5 years. Conclusions: A cluster of platelet-based indices combined with other clinical covariates could be used for prognosis evaluation in HCC.

Effects of 17β-Estradiol on Colonic Permeability and Inflammation in an Azoxymethane/Dextran Sulfate Sodium-Induced Colitis Mouse Model

  • Song, Chin-Hee;Kim, Nayoung;Sohn, Sung Hwa;Lee, Sun Min;Nam, Ryoung Hee;Na, Hee Young;Lee, Dong Ho;Surh, Young-Joon
    • Gut and Liver
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    • v.12 no.6
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    • pp.682-693
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    • 2018
  • Background/Aims: Intestinal barrier dysfunction is a hallmark of inflammatory bowel diseases (IBDs) such as ulcerative colitis. This dysfunction is caused by increased permeability and the loss of tight junctions in intestinal epithelial cells. The aim of this study was to investigate whether estradiol treatment reduces colonic permeability, tight junction disruption, and inflammation in an azoxymethane (AOM)/dextran sodium sulfate (DSS) colon cancer mouse model. Methods: The effects of $17{\beta}$-estradiol (E2) were evaluated in ICR male mice 4 weeks after AOM/DSS treatment. Histological damage was scored by hematoxylin and eosin staining and the levels of the colonic mucosal cytokine myeloperoxidase (MPO) were assessed by enzyme-linked immunosorbent assay (ELISA). To evaluate the effects of E2 on intestinal permeability, tight junctions, and inflammation, we performed quantitative real-time polymerase chain reaction and Western blot analysis. Furthermore, the expression levels of mucin 2 (MUC2) and mucin 4 (MUC4) were measured as target genes for intestinal permeability, whereas zonula occludens 1 (ZO-1), occludin (OCLN), and claudin 4 (CLDN4) served as target genes for the tight junctions. Results: The colitis-mediated induced damage score and MPO activity were reduced by E2 treatment (p<0.05). In addition, the mRNA expression levels of intestinal barrier-related molecules (i.e., MUC2, ZO-1, OCLN, and CLDN4) were decreased by AOM/DSS-treatment; furthermore, this inhibition was rescued by E2 supplementation. The mRNA and protein expression of inflammation-related genes (i.e., KLF4, NF-${\kappa}B$, iNOS, and COX-2) was increased by AOM/DSS-treatment and ameliorated by E2. Conclusions: E2 acts through the estrogen receptor ${\beta}$ signaling pathway to elicit anti-inflammatory effects on intestinal barrier by inducing the expression of MUC2 and tight junction molecules and inhibiting pro-inflammatory cytokines.