• 제목/요약/키워드: Inducible nitric oxide

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Effects of Tributyrin on Intestinal Energy Status, Antioxidative Capacity and Immune Response to Lipopolysaccharide Challenge in Broilers

  • Li, Jiaolong;Hou, Yongqing;Yi, Dan;Zhang, Jun;Wang, Lei;Qiu, Hongyi;Ding, Binying;Gong, Joshua
    • Asian-Australasian Journal of Animal Sciences
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    • v.28 no.12
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    • pp.1784-1793
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    • 2015
  • This study was carried out to investigate the effects of tributyrin (TB) on the growth performance, pro-inflammatory cytokines, intestinal morphology, energy status, disaccharidase activity, and antioxidative capacity of broilers challenged with lipopolysaccharide (LPS). A total of 160 one-day-old Cobb broilers were allocated to 1 of 4 treatments, with 4 replicated pens per treatment and 10 birds per pen. The experiment consisted of a $2{\times}2$ factorial arrangements of treatments with TB supplementation (0 or 500 mg/kg) and LPS challenge (0 or $500{\mu}g/kg$ body weight [BW]). On days 22, 24, and 26 of the trial, broilers received an intraperitoneal administration of $500{\mu}g/kg$ BW LPS or saline. Dietary TB showed no effect on growth performance. However, LPS challenge decreased the average daily gain of broilers from day 22 to day 26 of the trial. Dietary TB supplementation inhibited the increase of interleukin-$1{\beta}$ (in the jejunum and ileum), interleukin-6 (in the duodenum and jejunum), and prostaglandin $E_2$ (in the duodenum) of LPS-challenged broilers. Similar inhibitory effects of TB in the activities of total nitric oxide synthase (in the ileum) and inducible nitric oxide synthase (in the jejunum) were also observed in birds challenged with LPS. Additionally, TB supplementation mitigated the decrease of ileal adenosine triphosphate, adenosine diphosphate and total adenine nucleotide and the reduction of jejunal catalase activity induced by LPS. Taken together, these results suggest that the TB supplementation was able to reduce the release of pro-inflammatory cytokines and improve the energy status and anti-oxidative capacity in the small intestine of LPS-challenged broilers.

Inhibition of NO Production by Ethanol Extract of Prunus mume Fruits in LPS-Stimulated RAW 264.7 Macrophages through Regulation of the Nrf2/HO-1 Signaling Pathway (LPS가 처리된 RAW 264.7 대식세포에서 Nrf2/HO-1 경로 조절을 통한 매실 추출물의 NO 생성 억제 효과)

  • Kang, Hye-Joo;Choi, Eun Ok;Jeong, Jin-Woo;Park, Shin-Hyung;Park, Cheol;Hong, Su Hyun;Shin, Soon Shik;Cheong, Jae-Hun;Choi, Yung Hyun
    • Herbal Formula Science
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    • v.25 no.1
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    • pp.1-10
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    • 2017
  • Objectives : The fruit of Prunus mume Siebold & Zucc. has been used as an alternative medicine and functional food in Korea and Japan for preventive and therapeutic purposes. However, its molecular actions and mechanism on anti-inflammatory activity have not been clearly investigated. The aim of this study was to clarify the anti-inflammatory activity of the ethanol extract of P. mume fruit (EEPM) in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells, and sought to understand the associated molecular mechanisms. Methods : Cytotoxicity was assessed by an MTT assay. The amount of nitric oxide (NO) production was determined by nitrite assay. The mRNA expression of inducible nitric oxide synthase (iNOS) was analyzed by RT-PCR. In addition, expression levels of iNOS, nuclear factor-erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) protein were detected by Western blotting. Results : Our data indicated that EEPM inhibited NO production in LPS-stimulated RAW264.7 cells in a concentration-dependent manner. At the mRNA and protein levels, EEPM suppressed LPS-induced iNOS expression. On the other hand, EEPM markedly enhanced HO-1 expression, which was associated with an induction and nuclear translocation of Nrf2. Moreover, the inhibitory effect of EEPM against LPS‑induced NO production was significantly enhanced by hemin, a HO-1 inducer; however, EEPM's effect on the production of NO was abolished by zinc protoporphyrin IX, a HO-1 inhibitor. Conclusion : The results suggest that EEPM can act as a suppressor agent on NO production through an activation of Nrf2/HO-1 signaling pathway, and may be a promising candidate for the treatment of inflammatory diseases.

Transduced PEP-1-AMPK inhibits the LPS-induced expression of COX-2 and iNOS in Raw264.7 cells

  • Shin, Min-Jea;Lee, Yeom-Pyo;Kim, Dae-Won;An, Jae-Jin;Jang, Sang-Ho;Cho, Sung-Min;Sheen, Seung-Hoon;Lee, Hae-Ran;Kweon, Hae-Yong;Kang, Seok-Woo;Lee, Kwang-Gill;Park, Jin-Seu;Eum, Won-Sik;Cho, Yong-Jun;Choi, Soo-Young
    • BMB Reports
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    • v.43 no.1
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    • pp.40-45
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    • 2010
  • AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that plays a central role in cellular metabolic stress. Modulation of nitric oxide (NO) and cyclooxygenase-2 (COX-2) is considered a promising approach for the treatment of inflammation and neuronal diseases. In this study, the AMPK gene was fused in-frame with PEP-1 peptide in a bacterial expression vector to produce a PEP-1-AMPK fusion protein. Expressed and purified PEP-1-AMPK fusion proteins were transduced efficiently into macrophage Raw 264.7 cells in a time- and dose-dependent manner. Furthermore, transduced PEP-1-AMPK fusion protein markedly inhibited LPS-induced iNOS and COX-2 expression. These results suggest that the PEP-1-AMPK fusion protein can be used for the protein therapy of COX-2 and NO-related disorders such as inflammation and neuronal diseases.

Anti-Inflammatory Activity of Ethanol Extracts from Hizikia fusiformis Fermented with Lactic Acid Bacteria in LPS-Stimulated RAW264.7 Macrophages (유산균 종류에 따른 발효톳 추출물의 항염증 활성)

  • Kwon, Myeong Sook;Mun, Ok-Ju;Bae, Min Joo;Lee, Seul-Gi;Kim, Mihyang;Lee, Sang-Hyeon;Yu, Ki Hwan;Kim, Yuck Yong;Kong, Chang-Suk
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.10
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    • pp.1450-1457
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    • 2015
  • The anti-inflammatory effect of ethanol extracts from Hizikia fusiformis fermented with and without lactic acid bacteria was compared in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophages. The fermentation was done using Weissella sp. SH-1 and Lactobacillus casei in a mixture of glucose and lactate source at $30^{\circ}C$ for 30 days. As a result, we confirmed that the fermentation of H. fusiformis with lactic acid bacteria inhibited LPS-stimulated nitric oxide (NO) production and the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, interleukin (IL)-6, tumor necrosis factor ${\alpha}$, and IL-$1{\beta}$ as important inflammatory factors. During a comparison analysis, we found that L. casei fermented groups significantly suppressed NO production by regulating iNOS and COX-2 expression. Also, the effective suppression of pro-inflammatory cytokine and LPS-induced activation of mitogen- activated protein kinase indicated that the fermentation using Weissella sp. SH-1 and L. casei may provide an increment towards the extraction of active components, which are effective anti-inflammatory agents.

Anti-inflammatory Effects of Ethanolic Extracts from Codium fragile on LPS-Stimulated RAW 264.7 Macrophages via Nuclear Factor kappaB Inactivation

  • Yoon, Ho-Dong;Jeong, Eun-Ji;Choi, Ji-Woong;Lee, Min-Sup;Park, Myoung-Ae;Yoon, Na-Young;Kim, Yeon-Kye;Cho, Deuk-Moon;Kim, Jae-Il;Kim, Hyeung-Rak
    • Fisheries and Aquatic Sciences
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    • v.14 no.4
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    • pp.267-274
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    • 2011
  • Bacterial lipopolysaccharide (LPS) induces expression of pro-inflammatory cytokines and enzymes producing nitric oxide (NO) and prostaglandins (PGs) in immune cells. This process is mediated by the activation of nuclear factor kappaB (NF-${\kappa}B$). In this study, we investigated the anti-inflammatory characteristics of Codium fragile ethanolic extract (CFE) mediated by the regulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) using LPS-stimulated murine macrophage RAW 264.7 cells. CFE significantly inhibited LPS-induced NO and $PGE_2$ production in a dose-dependent manner and suppressed the expression of iNOS and COX-2 proteins in LPS-stimulated RAW 264.7 cells with no cytotoxicity. Pro-inflammatory cytokines, such as interleukin (IL)-$1{\beta}$, IL-6, and tumor necrosis factor-${\alpha}$, were significantly reduced by treatment of CFE in LPS-stimulated RAW 264.7 cells. CFE inhibited the promoter activity of (NF)-${\kappa}B$ in LPS-stimulated macrophages. Treatment with CFE suppressed translocation of the NF-${\kappa}B$ p65 subunit by preventing proteolytic degradation of inhibitor of ${\kappa}B-{\alpha}$. These results indicate that the CFE-mediated inhibition of NO and $PGE_2$ production in LPS-stimulated RAW 264.7 cells is mediated through the NF-${\kappa}B$-dependent transcriptional downregulation of iNOS and COX-2, suggesting the potential of CFE as a nutraceutical with anti-inflammatory activity.

Inhibitory effect of Koreinsis chinensis leaves extract on proinflammatory responses in lipopolysaccharide-induced Raw 264.7 cells (Lipopolysaccharide로 유도된 Raw 264.7 cell에서 잣 잎(Koreinsis chinensis L.) 추출물의 Pro-inflammatory 억제 효과)

  • Cho, Young-Je
    • Journal of Applied Biological Chemistry
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    • v.60 no.3
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    • pp.191-198
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    • 2017
  • Hyaluronidase inhibitory activity as inflammatory factor of Koreinsis chinensis leaf ethanol extract was showed higher inhibitory activity than water extract. 29.5% inhibitory activity was shown at concentration of $200{\mu}g/mL$ phenolics. Lipopolysaccharide (LPS)-stimulated Raw 264.7 cells were treated with different concentrations ($5-25{\mu}g/mL$) of Koreinsis chinensis leaf extract and the amount of nitric oxide (NO) was determined; LPS-treated cells produced 3 times more NO than non-LPS treated cells. Moreover, the NO production in cells treated with Koreinsis chinensis leaf extract showed inhibitory effect in a concentration-dependent manner. Due to the stimulant-induced NO production is regulated by the inducible nitric oxide synthase (iNOS), we determined the iNOS protein level to elucidate the mechanism by which the NO production was inhibited. It was reduced by 40% with a Koreinsis chinensis leaf extract concentration of $25{\mu}g/mL$ and identified iNOS inhibition in dose-dependent manner. The prostaglandin $E_2$ production in cells treated with Koreinsis chinensis leaf extract was reduced by 26.2% at concentration of $25{\mu}g/mL$. The protein expression of cyclooxygenase-2 in LPS-treated Raw 264.7 cells was inhibited by 64% at $25{\mu}g/mL$ of Koreinsis chinensis leaf extract. Koreinsis chinensis leaf extract had a concentration-dependent inhibitory effect on the production of tumor necrosis factor-${\alpha}$ and interleukin-6 as pro-inflammatory cytokine in LPS-treated Raw 264.7 cells at $25{\mu}g/mL$ of Koreinsis chinensis leaf extract. Their levels were decreased by 61.7 and 62% respectively.

Anti-inflammatory Constituents of the Aerial Parts of Trichosanthes kirilowii in BV2 Microglial Cells (괄루경엽의 BV2 미세아교세포에서의 항염증 활성 성분)

  • Li, Xiao Jun;Kim, Kwan-Woo;Ko, Wonmin;Kim, Dong-Cheol;Yoon, Chi-Su;Liu, Xiang Qian;Kim, Jong-Su;Jang, Kyu-Kwan;Kang, Dae-Gil;Lee, Ho-Sub;Oh, Hyuncheol;Kim, Youn-Chul
    • Korean Journal of Pharmacognosy
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    • v.47 no.1
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    • pp.7-11
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    • 2016
  • The aerial part of Trichosanthes kirilowii Maxim. (Cucurbitaceae), has long been used in traditional Korean and Chinese medicines for the treatment of heatstroke. We isolated and identified three flavones, luteolin-7-O-${\beta}$-D-glucopyranoside(1), luteolin-4'-O-${\beta}$-D-glucopyranoside(2), luteolin(3) from its methanolic extract. In the present study, we found that luteolin attenuates the lipopolysaccharide(LPS)-induced inflammation in BV2 microglial cells. Luteolin significantly inhibited LPS-induced production of pro-inflammatory mediators such as nitric oxide(NO) and prostaglandin $E_2(PGE_2)$ in BV2 microglia in a concentration-dependent manner without cytotoxic effect. Luteolin dose-dependently suppressed the protein expression of inducible nitric oxide synthase(iNOS) and cyclooxygenase-2(COX-2). In addition, luteolin also showed significant induction of heme oxygenase(HO)-1. These results suggest that both the aerial part of T. kirilowii and luteolin may be good candidates to regulate LPS-induced inflammatory response.

Anti-inflammatory effects of a mixture of coffee and sword bean extracts (커피와 작두콩 추출물의 혼합에 따른 항염증 효과)

  • Bae, Hun Cheon;Park, Jung Up;Moon, Jae-Hak
    • Korean Journal of Food Science and Technology
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    • v.52 no.3
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    • pp.237-243
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    • 2020
  • Coffee is one of the most widely consumed beverages in the world, and sword bean (Canavalia gladiata, SB) reportedly possesses various biological activities. Therefore, in this study, to reduce caffeine intake and improve coffee function, SB was selected as a supplementary material for blending coffee. The antioxidant and anti-inflammatory activities of coffee with the SB extract at concentrations of 0.1-0.5% (v/v) were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and RAW 264.7 cells, respectively. The DPPH radical-scavenging activity of SB-treated coffee depended on the concentration of the SB extract. In the cell culture experiment, cytotoxicity was not observed at any SB concentration. In addition, the inducible nitric oxide synthesis protein expression as well as the increases in nitric oxide and interleukin-6 expression were effectively inhibited by SB addition to the coffee. These results indicate that SB might be useful as a supplementary ingredient to enhance the caffeinated drink functions.

The Anti-oxidative and Anti-inflammatory Activities of Malus melliana Ethanol Extract (Malus melliana 에탄올 추출물의 항산화 및 항염증 활성)

  • Lee, Su Hyeon;Jin, Kyong-Suk;Kim, Byung Woo;Kwon, Hyun Ju
    • Journal of Life Science
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    • v.27 no.7
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    • pp.783-789
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    • 2017
  • Malus melliana (Hand.-Mazz.) Rehder (M. melliana) is a Chinese plant that belongs to the Rosaceae family. There have been no previous reports regarding its bioactivity. In this study, the anti-oxidative and anti-inflammatory activities of M. melliana ethanol extract (MMEE) were evaluated using a 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging activity assay, reactive oxygen species (ROS) scavenging activity assay, nitric oxide (NO) inhibitory activity assay, and the analysis of related protein expressions through Western blot hybridization. MMEE showed potent scavenging activity against DPPH, similar to ascorbic acid, a well-known anti-oxidative agent, which was used as a positive control. MMEE also inhibited hydrogen peroxide-induced ROS in RAW 264.7 cells. Moreover, MMEE induced the expression of an anti-oxidative enzyme, heme oxygenase 1, and its upstream transcription factor, nuclear factor E2-related factor-2, in a dose-dependent manner. On the other hand, MMEE was associated with a reduction in NO production, which was induced by the lipopolysaccharide treatment of RAW 264.7 cells. The expression of inducible nitric oxide synthase, which is the upstream regulator of NO production, was also inhibited. Taken together, these results suggest that MMEE has anti-oxidative and anti-inflammatory properties, thus appearing to be a potential anti-oxidant and anti-inflammatory agent. The further identification of active compounds that confer the biological activities of MMEE may be necessary.

Anti-inflammatory Effects of Heat-treated Starfish Extract in Lipopolysaccharide-stimulated RAW 264.7 Cells (열처리 불가사리 추출물의 항염 활성)

  • Park, Jae Hyeon;Ahn, Keun Jae;Lee, Sun-Ryung
    • Journal of Life Science
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    • v.30 no.7
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    • pp.634-639
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    • 2020
  • Starfish are a potential source of marine materials, but their unique odor can limit application. Our previous work suggested that brittle star Ophioplocus japonicus extract could be more effective as a cosmetic material by reducing its odor through a roasting process. However, the biological properties of heat-treated Ophioplocus japonicus extract (HOJE) remain poorly understood. We here examined the anti-inflammatory potential of HOJE in lipopolysaccharide (LPS)-induced RAW 264.7 cells. HOJE significantly inhibits LPS-stimulated nitric oxide (NO) production without affecting cell viability in a dose-dependent manner and suppresses LPS-induced expression of inducible nitric oxide synthases (iNOS) and pro-inflammatory cytokines such as interleukin-6 and -1β. Furthermore, treatment of pyrrolidine dithiocarbamate to inhibit nuclear factor kappa B (NF-κB) signaling accelerated the inhibitory effect of HOJE on NO production, and the translocation of NF-κB p65 from the cytosol to the nucleus was attenuated by HOJE. These results show that HOJE ameliorates inflammation partly through NF-κB signaling which consequently suggests that it has anti-inflammatory potential.