• Title/Summary/Keyword: iNOS, TNF-$\alpha$

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Hepatic Vascular Stress Gene Expression in the Liver Response to Trauma

  • Lee, Sun-Mee
    • Biomolecules & Therapeutics
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    • v.12 no.2
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    • pp.62-67
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    • 2004
  • Trauma remains one of the important sources leading to systemic inflammatory response anti sub-sequent multiple organ failure. Although hepatic microvascular dysfunction occurs during trauma, the mechanism responsible remains unclear. The aim of this study was to investigate the effect of trauma on hepatic vascular stress gene expression. Femur fracture (EFx) was induced by torsion to the femur at midshaft. Liver samples were taken for RT-PCR analysis of mRNA for gtenes of interest: endothelin-1 (ET-1), its receptors $ET_A$ and $ET_B$, nitric oxide synthases (iNOS and eNOS), cyclooxygenase-2 (COX-2), heme oxygenase-1 (HO-1), and tumor necrosis tactor-${\alpha}$ (TNF-${\alpha}$). The expression of ET-1 mRNA was significantly increased by FFx. Expression of mRNA in FFx group showed no change in $ET_A$, $ET_B$, iNOS and HO-1 and showed a slight increase of 2.2-fold and 2.7-fold for eNOS tll1d COX-2, respectively. The level of TNF-${\alpha}$ mRNA significantly increased in FFx group. In conclusion, mild trauma alone causes little change in expression of vasoactive mediators.

Anti-inflammatory Effects of Cnidium Rhizoma against Intracerebral Hemorrhage in Rats (천궁(川芎)의 뇌조직출혈 흰쥐 힝염증반응에 대한 연구)

  • Baek, Dong-Ha;Kim, Do-Hoon;Kim, Youn-Sub
    • The Korea Journal of Herbology
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    • v.29 no.2
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    • pp.33-38
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    • 2014
  • Objectives : Inflammation is mediated by cellular components, such as leukocytes and microglia, and molecular components, including cytokines, extracellular proteases, and reactive oxygen species. Cnidium Rhizoma effects the anti-inflammatory, antioxidant, suppression of the microglia activation and protection of the nerve cell injury. For this reason, we investigated the anti-inflammatory effects of water extracts of Cnidium Rhizoma on intracerebral hemorrhage (ICH). Method : ICH was induced by the stereotaxic intracerebral injection of bacterial collagenase type IV (0.23 $U/{\mu}{\ell}$, 0.1 ${\mu}{\ell}/min$) in Sprague-Dawley rats. We orally administrated once 3 hours after ICH, then 2 times at 24-hour intervals the water extracts of Cnidium Rhizoma (500 mg/kg), myeloperoxidase (MPO) was observed by using immunofluorescense and expression of inducible nitric oxide synthase (iNOS), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and microglia were observed by using immunohistochemistry. Results : Infiltration of MPO expressing neutrophil, expression of iNOS and TNF-${\alpha}$ and activated microglia were significantly reduced in peri-hematoma of the rats fed with water extracts of Cnidium Rhizoma. Conclusion : These results demonstrated that water extracts of Cnidium Rhizoma suppressed an inflammatory reaction through inhibition of MPO, iNOS and TNF-${\alpha}$ positive cell and activated microglia number in peri-hematoma of ICH-induced rats.

Inhibitory Effect of the Leaves of Rumex crispus L. on LPS-induced Nitric Oxide Production and the Expression of iNOS and COX-2 in Macrophages

  • Im, Nam-Kyung;Jung, Yeon-Seop;Choi, Jun-Hyeok;Yu, Mi-Hee;Jeong, Gil-Saeng
    • Natural Product Sciences
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    • v.20 no.1
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    • pp.51-57
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    • 2014
  • In this study, the anti-inflammatory effects of ethanol extract of Rumex crispus L. and its fractions were investigated in RAW 264.7 macrophages. To evaluate the anti-inflammatory effects of extract, we studied nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and tumor necrosis factor-alpha ($TNF-{\alpha}$) levels in RAW 264.7 cells. The ethanol extract of R. crispus L. significantly decreased NO production and the levels of other inflammatory factors, such as PGE2 and $TNF-{\alpha}$, in lipopolysaccharide (LPS)-stimulated macrophages in a dose-dependent manner. We also assessed the inducible nitric oxide synthase (iNOS) and the cyclooxygenase 2 (COX-2) protein expression by western blot. Ethyl acetate fraction of R. crispus L. had the strongest anti-inflammatory effect. These results suggest that ethyl acetate extract of R. crispus L. might be beneficial in the treatment of chronic inflammatory diseases.

Inhibition of LPS induced iNOS, COX-2 and cytokines expression by kaempferol-3-O-${\beta}$-D-sophoroside through the $NF{-\kappa}B$ inactivation in RAW 264.7 cells (Kaempferol-3-O-${\beta}$-D-sophoroside의 RAW 264.7 세포에서 $NF{-\kappa}B$ 억제를 통한 LPS에 의해 유도되는 iNOS, COX-2 및 cytokine들의 발현 저해효과)

  • Park, Seung-Jae;Shin, Ji-Sun;Cho, Woong;Cho, Young-Wuk;Ahn, Eun-Mi;Baek, Nam-In;Lee, Kyung-Tae
    • Korean Journal of Pharmacognosy
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    • v.39 no.2
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    • pp.95-103
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    • 2008
  • In the present study, we investigated the anti-inflammatory effects by kaempferol-3-O-${\beta}$-D-sophoroside (KS) isolated from Sophora japonica (Leguminosae) on the lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin ($PGE_2$) production by RAW 264.7 cell line compared with kaempferol. KS significantly inhibited the LPS-induced NO and $PGE_2$ production. Consistent with these observations, KS reduced the LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels in a concentration-dependent manner. In addition, the release and the mRNA expression levels of tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and interleukin-6 (IL-6) were also reduced by KS. Moreover, KS attenuated the LPS-induced activation of nuclear factor-kappa B ($NF{-\kappa}B$), a transcription factor necessary for pro-inflammatory mediators, iNOS, COX-2, $TNF-{\alpha}$ and IL-6 expression. These results suggest that the down regulation of iNOS, COX-2, $TNF-{\alpha}$, and IL-6 expression by KS are achieved by the downregulation of $NF{-\kappa}B$ activity, and that is also responsible for its anti-inflammatory effects.

Inhibitory Effect of Eurya emarginata on the Production of Pro-inflammatory Cytokines in Murine Macrophage RAW264.7 (Murine Macrophage RAW 264.7 세포에서 우묵사스레피에 의한 염증성 사이토카인 억제효과)

  • 박수영;이혜자;현은아;문지영;앙홍철;이남호;김세재;강희경;유은숙
    • YAKHAK HOEJI
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    • v.47 no.5
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    • pp.311-318
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    • 2003
  • Eurya emarginata (Thunb.) Makino (Theaceae) is distributed in coastal areas of island. The leaves of Eurya are used in the traditional medicine of the coastal areas of jeju island with the aim of diuresis or to treat ulcers. Nevertheless, there are few reports on the biological activity and constituents of E. emarginata. In this study, we investigated the pharmacological activity of the solvent extracts of E. emarginata on the several inflammatory markers (TNF-$\alpha$, IL-1$\beta$, IL-6, NO, iNOS and COX-2). Also we examined the antioxidizing effect of the solvent extracts by determination of DPPH radical-scavenging activity. Among the solvent fractions, EtOAc and BuOH extracts showed potent radical scavenging activity (RC$_{50}$=10.9 and 12.7 respectively). The subtractions of EF 5-4-6-3-2 and BF 1 potentially inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) at the concentration of 100 $\mu\textrm{g}$/mι. Also the fractions inhibited the mRNA expression of pro-inflammatory cytokines (IL-1$\beta$, IL-6 and TNF-$\alpha$) and protein expression of iNOS and COX-2 at the concentration of 100 $\mu\textrm{g}$/mι. And then, the inhibition of iNOS was correlated with the decrease of nitrite level. These results suggest that E. emarginata may have anti-inflammatory activity through the inhibition of pro-inflammatory cytokines, iNOS and COX-2.2.

Oral Concentrated Grape Juice Suppresses Expression of NF-kappa B, TNF-α and iNOS in Experimentally Induced Colorectal Carcinogenesis in Wistar Rats

  • de Lima Pazine Campanholo, Vanessa Maria;Silva, Roseane Mendes;Silva, Tiago Donizetti;Neto, Ricardo Artigiani;Paiotti, Ana Paula Ribeiro;Ribeiro, Daniel Araki;Forones, Nora Manoukian
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.947-952
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    • 2015
  • The aim of this study was to evaluate the effects of grape juice on colon carcinogenesis induced by azoxymethane (AOM) and expression of NF-kB, iNOS and TNF-${\alpha}$. Methods: Forty male Wistar rats were divided into 7 groups: G1, control; G2, 15 mg/kg AOM; G3, 1% grape juice 2 weeks before AOM; G4, 2% grape juice 2 weeks before AOM; G5, 1% grape juice 4 weeks after AOM; G6, 2% grape juice 4 weeks after AOM; G7, 2% grape juice without AOM. Histological changes and aberrant crypt foci (ACF) were studied, while RNA expression of NF-kB, TNF- and iNOS was evaluated by qPCR. Results: The number of ACF was higher in G2, and G4 presented a smaller number of crypts per focus than G5 (p=0.009) and G6. Small ACF (1-3) were more frequent in G4 compared to G2, G5 and G6 (p=0.009, p=0.009 and p=0.041, respectively). RNA expression of NF-kB was lower in G3 and G4 compared to G2 (p=0.004 and p=0.002, respectively). A positive correlation was observed between TNF-${\alpha}$ and NF-kB gene expression (p=0.002). In conclusion, the administration of 2% grape juice before AOM reduced the crypt multiplicity, attenuating carcinogenesis. Lower expression of NF-kB was observed in animals exposed to grape juice for a longer period of time, regardless of concentration.

Inhibition of LPS-induced iNOS, COX-2 Expression and Cytokines Production by Fupenjic Acid in Macrophage Cells (Fupenjic Acid의 대식세포에서 LPS에 의해 유도되는 iNOS와 COX-2 발현 및 Cytokine들의 생성 저해 효과)

  • Yun, Chang-Hyeon;Shin, Ji-Sun;Park, Hee-Juhn;Park, Jong-Hee;Lee, Kyung-Tae
    • Korean Journal of Pharmacognosy
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    • v.41 no.1
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    • pp.14-20
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    • 2010
  • In this study, we investigated the anti-inflammatory effects of fupenjic acid (FA) isolated from the Potentilla discolor in both RAW 264.7 and mouse primary peritoneal macrophage cells. FA pretreatment significantly inhibited nitric oxide (NO) and prostaglandin $E_2(PGE_2)$ productions in the lipopolysaccharide (LPS)-induced RAW 264.7 and mouse primary peritoneal macrophage cells. Consistent with these observations, Western blot and RT-PCR analyses revealed that FA inhibited the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the protein and mRNA levels. In addition, FA reduced the release of tumor necrosis factor-$\alpha$ (TNF-$\alpha$) and interleukin-6 (IL-6). These results suggest that the down regulation of iNOS and COX-2 expression and TNF-$\alpha$ and IL-6 production by fupenjic acid are responsible for its anti-inflammatory effects.

Anti-inflammatory and Immune Regulatory Effects of Aucklandia lappa Decne 70% Ethanol Extract (운목향 70% 에탄올 추출물의 항염증 및 면역조절에 대한 효과)

  • Kim, Min Sun;Kim, Nam Seok;Kwon, Jin;Kim, Ha Rim;Lee, Da Young;Oh, Mi Jin;Kim, Hong Jun;Lee, Chang Hyun;Oh, Chan Ho
    • Korean Journal of Medicinal Crop Science
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    • v.26 no.1
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    • pp.8-18
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    • 2018
  • Background: This present study was conducted to evaluate the anti-inflammatory and immune regulatory effects of Aucklandia lappa Decne (AL). Methods and Results: We measured cytotoxicity, nitric oxide (NO) content, mRNA expression (iNOS, IL-1${\alpha}$, IL-$1{\beta}$, and TNF-${\alpha}$), protein expression (iNOS, COX-2, and $I{\kappa}B$) and phagocytic activity in RAW264.7 cells. Male BALB/c mice were fed 100 mg/kg AL (Aucklandia lappa Decneon 70% ethanol extract) and 250 mg/kg AL for 4 weeks; thereafter, we observed B/T or $CD4^+/CD8^+$ lymphocyte subpopulation change, and expression patterns of $CD4^+$ and $CD8^+$ lymphocytes by immunohistochemical staining in mouse splenocytes and/or thymocytes. To determine the experimental concentration of AL, cell viability was measured by MTT assay and tested at $12.5{\mu}g/m{\ell}$ or less. AL inhibited the levels of NO, lymphokine production (IL-$1{\beta}$, and TNF-${\alpha}$), and mRNA (iNOS, IL-1${\alpha}$, IL-$1{\beta}$, and TNF-${\alpha}$) and protein (iNOS, and COX-2) expression. Additionally, the levels of $I{\kappa}B$, phagocytic activity, and splenic and thymic T lymphocytes, especially $T_H$ and $T_C$ cells were significantly increased in AL administered mice. The immuno-reactive density of $CD4^+$ and $CD8^+$ lymphocytes was stronger in AL groups than in the normal group. AL stimulated NO, iNOS, and COX-2, and regulated IL-1${\alpha}$, IL-$1{\beta}$, TNF-${\alpha}$, and $I{\kappa}B$ in macrophages treated with LPS (lipopolysaccharide). In addition, AL increased the phagocytic activity of macrophages and the immunity of mouse T ($T_H$, and $T_C$) cells. Conclusions: These results suggested that AL might show anti-inflammatory activity via the suppression of various inflammatory markers and immuno-regulatory activity.

Inhibition of lipopolysaccharide-induced inflammatory mediators NO, PGs, TNF-$\alpha$ expression by MeOH extract of Kochia scoparia in RAW264.7 cells.

  • Shin, Kyung-Min;Kim, Yang-Hee;Park, Wan-Soo;Lee, Kyung-Tae;Park, Hee-Jun;Choi, Jung-Won
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.214.1-214.1
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    • 2003
  • MeOH extract obtained from the Kochia scoparia (KS) was observed to inhibit tumor necrosis factor-alpha (TNF-alpha), prostaglandins (PGs) and nitric oxide(NO) production in a lipopolysaccharide (LPS)-stimulated murine macrophage cell line, RAW 264.7. These effects of MeOH-KS were based on modulation of iNOS and COX-2 level. Western blot analysis showed that MeOH-KS reduced the iNOS and COX-2 level in LPS activated macrophages, in a dose dependent manner without cNOS and COX-1 protein level. (omitted)

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Effects of Hyeolbuchukeo-tang (Xiefuzhuyutang) on NO Production in Aortic Vascular Smooth Muscle Cells (혈부축어탕이 대동맥 평골근 세포에서 NO 생성에 미치는 영향)

  • 한종민;고창보;박창민;정명수;박길래;이기남
    • The Journal of Korean Medicine
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    • v.23 no.2
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    • pp.19-27
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    • 2002
  • Objective : This study was designed to investigate the effect of Hyeolbuchukeo-tang (HCT) on NO production and the molecular mechanism of NO production modulated by HCT in the primary VSMC (vascular smooth muscle cells). Method : Primary VSMC was established from aorta and cultured VSMC used in this study. NO production of VSMC was assayed by Griess reagent and the expression of iNOS gene was assayed by Western, RT-PCR. Result : $TNF-{\gamma}$ induced NO production, but $IFN-{\gamma}$ or HCT alone did not induce NO production in cultured VSMC. However, $IFN-{\gamma}$ or HCT potentiated NO production in $TNF-{\gamma}-treated$ VSMC in a time- and dose-dependent manner. $TNF-{\gamma}$ induced the iNOS gene expression corresponding to NO production in $TNF-{\gamma}-treated$ VSMC. HCT potentiated NO production in $TNF-{\gamma}-treated$ VSMC by about 20%, but HCT did not increase the level of iNOS mRNA in $TNF-{\gamma}-treated$ VSMC. HCT slightly increased the level of iNOS protein in $TNF-{\gamma}-treated$ VSMC. Calcium ionophore A23187 decreased NO production in $TNF-{\gamma}-treated$ VSMC, but HCT attenuated the effect of A23187. Conclusion : As NO is deeply involved in the development of arteriosclerosis and dilation of blood vessels, drugs or chemicals modulating NO production in VSMC could be used for preventing and treating arteriosclerosis. Considering the effect of HCT on the modulation of NO production in VSMC, MCT has a potential capacity for preventing and treating diseases of the circulation system including arteriosclerosis.

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