• 제목/요약/키워드: iNOS expression

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프로안토시아니딘의 항염증효과 (Proanthocyanidins Suppresses Lipopolysaccharide-stimulated Inflammatory Responses via Heme Oxygenase-1 Induction in RAW264.7 Macrophages)

  • 천혜진;박선영;장희지;조다영;정지원;박기민;정경미;김진경
    • 생명과학회지
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    • 제29권4호
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    • pp.484-491
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    • 2019
  • 프로안토시아니딘(proanthocyanidins)은 식물계에 가장 풍부한 폴리페놀성 화합물로 다양한 고등식물의 뿌리, 잎, 열매, 나무껍질 등에 널리 존재할 뿐만 아니라 이러한 원료로 만들어진 차, 와인, 맥주 등과 같은 식품에도 상당량 함유되어 있다. 세포 및 실험동물을 이용한 다수의 연구보고에 의하면 프로안토시아니딘은 항산화활성 및 면역조절활성, DNA 복구 및 항종양 작용과 같은 인체 건강에 유익한 무수한 효과를 가지고 있는 것으로 밝혀졌다. 면역 세포 중 대식세포(macrophage)는 염증반응을 매개하는 중요한 세포로 외부 병원체 제거에 중요한 역할을 수행하고 있다. 그러나 대식세포가 만성 염증을 유발하고 비만, 당뇨병, 대사 증후군 및 암과 같은 다양한 질병에 관여한다는 것 또한 널리 보고되어왔다. 본 연구에서는 마우스의 대식세포주인 RAW264.7세포를 이용하여 프로안토시아니딘의 항염증활성의 일단이 Heme oxygenase-1 (HO-1)의 유도에 의해서 매개됨을 밝혔다. RAW264.7세포에 프로안토시아니딘을 처리한 결과 세포독성을 보이지 않은 농도에서 HO-1의 발현을 증강시켰다. 또한 프로안토시아니딘의 처리는 HO-1의 발현을 조절하는 핵심 전사인자인 Nrf (nuclear factor-erythroid 2-related factor)-2의 핵으로의 이동을 유의적으로 증가시켰다. 프로안토시아닌딘의 처리는 LPS (lipopolysaccharide)에 의해 유도된 NO (nitric oxide)의 생성 및 iNOS (inducible NO synthase)의 발현과 염증성 사이토카인의 생성 및 발현도 유의적으로 억제 하였다. 이러한 결과는 프로안토시아니딘의 항염증제제로서의 개발 가능성을 제시하는 결과이다.

Effects of a Tetramethoxyhydroxyflavone on the Expression of Inflammatory Mediators in LPS-Treated Human Synovial Fibroblast and Macrophage Cells

  • Yoon, Do-Young;Cho, Min-Chul;Kim, Jung-Hee;Kim, Eun-Jin;Kang, Jeong-Woo;Seo, Eun-Hee;Shim, Jung-Hyun;Kim, Soo-Hyun;Lee, Hee-Gu;Oh, Goo-Taeg;Hong, Jin-Tae;Park, Joo-Won;Kim, Jong-Wan
    • Journal of Microbiology and Biotechnology
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    • 제18권4호
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    • pp.686-694
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    • 2008
  • The inhibitory effects of 5,6,3',5'-tetramethoxy 7,4'-hydroxyflavone (labeled as p7F) were elucidated on the productions of proinflammatory cytokines as well as inflammatory mediators in human synovial fibroblasts and macrophage cells. p7F inhibited IL-1${\beta}$ or TNF-${\alpha}$ induced expressions of inflammatory mediators (ICAM-1, COX-2, and iNOS). p7F also inhibited LPS-induced productions of nitric oxide and prostaglandin $E_2$ in RAW 264.7 cells. In order to investigate whether p7F would inhibit IL-1 signaling, p7F was added to the D10S Th2 cell line (which is responsive to only IL-1${\beta}$ and thus proliferates), revealing that p7F inhibited IL-1${\beta}$-induced proliferation of D10S Th2 cells in a dose-response manner. A flow cytometric analysis revealed that p7F reduced the intracellular level of free radical oxygen species in RAW 264.7 cells treated with hydrogen peroxide. p7F inhibited IkB degradation and NF-${\kappa}$B activation in macrophage cells treated with LPS, supporting that p7F could inhibit signaling mediated via toll-like receptor. Taken together, p7F has inhibitory effects on LPS-induced productions of inflammatory mediators on human synovial fibroblasts and macrophage cells and thus has the potential to be an anti-inflammatory agent for inhibiting inflammatory responses.

Effects of plant-based Korean food extracts on lipopolysaccharide-stimulated production of inflammatory mediators in vitro

  • Lee, Sun Young;Kim, Yoo-Sun;Lim, Ji Ye;Chang, Namsoo;Kang, Myung-Hee;Oh, Se-Young;Lee, He-Jin;Kim, Hyesook;Kim, Yuri
    • Nutrition Research and Practice
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    • 제8권3호
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    • pp.249-256
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    • 2014
  • BACKGROUND/OBJECTIVES: The traditional Korean diet is plant-based and rich in antioxidants. Previous studies have investigated the potential health benefits of individual nutrients of Korean foods. However, the cumulative effects of a Korean diet on inflammation remain poorly understood. Therefore, the aim of this study was to investigate the anti-inflammatory effects of a plant-based Korean diet. MATERIALS/METHODS: Using data from the Fifth Korean National Health and Nutrition Examination Survey, 75 individual plant food items were selected which represent over 1% of the total diet intake of the Korean diet. These items were classified into ten different food groups, and the vegetable (Veg) and fruit (Fruit) groups were studied based on their high antioxidant capacity. For comparison, a mixture of all ten groups (Mix) was prepared. To produce a model of inflammation with which to test these Veg, Fruit, and Mix plant-based Korean food extracts (PKE), RAW264.7 macrophages were treated with lipopolysaccharide (LPS). RESULTS: Levels of nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), as well as protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) were found to be lower following PKE treatment. Furthermore, PKE treatment was found to suppress tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and interleukin-6 (IL-6) via the nuclear transcription factor kappa-B ($NF-{\kappa}B$) signaling pathway. Overall, the Mix group exhibited the greatest anti-inflammatory effects compared with Veg and Fruit PKE group. CONCLUSIONS: Inhibition of LPS-induced pro-inflammatory mediators by the PKE tested was found to involve an inhibition of NF-kB activation. Moreover, PKE tested have the potential to ameliorate various inflammation-related diseases by limiting the excessive production of pro-inflammatory mediators.

Anti-Inflammatory Activity of Oligomeric Proanthocyanidins Via Inhibition of NF-κB and MAPK in LPS-Stimulated MAC-T Cells

  • Ma, Xiao;Wang, Ruihong;Yu, Shitian;Lu, Guicong;Yu, Yongxiong;Jiang, Caode
    • Journal of Microbiology and Biotechnology
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    • 제30권10호
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    • pp.1458-1466
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    • 2020
  • Oligomeric proanthocyanidins (OPCs), classified as condensed tannins, have significant antioxidation, anti-inflammation and anti-cancer effects. This study was performed to investigate the anti-inflammatory effects of OPCs and the mechanism underlying these effects in lipopolysaccharide (LPS)-stimulated bovine mammary epithelial cells (MAC-T). Real-time PCR and ELISA assays indicated that OPC treatment at 1, 3 and 5 ㎍/ml significantly reduced the mRNA and protein, respectively, of oxidant indicators cyclooxygenase-2 (COX-2) (p < 0.05) and inducible nitric oxide synthase (iNOS) (p < 0.01) as well as inflammation cytokines interleukin (IL)-6 (p < 0.01), IL-1β (p < 0.01) and tumor necrosis factor-α (TNF-α) (p < 0.05) in LPS-induced MAC-T cells. Moreover, OPCs downregulated LPS-induced phosphorylation of p65 and inhibitor of nuclear factor kappa B (NF-κB) (IκB) in the NF-κB signaling pathway (p < 0.01), and they inhibited p65 translocation from the cytoplasm to the nucleus as revealed by immunofluorescence test and western blot. Additionally, OPCs decreased phosphorylation of p38, extracellular signal regulated kinase and c-jun NH2-terminal kinase in the MAPK signaling pathway (p < 0.01). In conclusion, the anti-inflammatory and antioxidant activities of OPCs involve NF-κB and MAPK signaling pathways, thus inhibiting expression of pro-inflammatory factors and oxidation indicators. These findings provide novel experimental evidence for the further practical application of OPCs in prevention and treatment of bovine mastitis.

대황 감초 복합추출물의 항산화 효과를 통한 역류성 식도염 개선 효과 (Improving Effect of a Combined Extract of Rhei Rhizoma and Glycyrrhizae Rhizoma through Anti-oxidative Stress in Reflux Esophagitis rats)

  • 김민영;신유옥;이주영;이아름;신성호;권오준;서부일;노성수
    • 대한본초학회지
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    • 제30권4호
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    • pp.37-44
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    • 2015
  • Objectives : The present study was designed to evaluate the anti-inflammatory and anti-oxidative stress activities through regulation of Nrf2-mediated genes by Rhei rhizoma and Glycyrrhiza rhizoma combined extract (RGE) in reflux esophagitis.Methods : The antioxidant activity of RGE in vitro was measured in terms of radical scavenging capacity such as DPPH and ABTS. RGE was administered at 350 mg/kg body weight prior to induction of reflux esophagitis. Reflux esophagitis was induced that tied the pylorus and the transitional junction between the forestomach and the corpus in Sprague-Dawley rats.Results : RGE scavenged DPPH and ABTS effectively and IC50of RGE each were 4.9 μg/ml and 45.6 μg/ml. Our results show that RGE administration markedly ameliorated mucosal damage upon histological evaluation. In serum and esophagus tissue, RGE significantly suppressed the oxidative stress biomarkers. Reflux esophagitis induced rats exhibited down-regulation of antioxidant-related proteins in the esophagus; however, the levels with treatment of RGE were significantly higher than those of vehicle reflux esophagitis rats. RGE treatment caused significant reductions in activation of NF-κB transcription factor. Thus, RGE significantly exhibited potent anti-inflammatory activities by suppressing the protein expression levels of pro-inflammatory proteins such as COX-2 and iNOS and inflammatory cytokines such as TNF-αin the esophagus tissue.Conclusions : Reflux esophagitis caused considerable levels of oxidative stress in the esophageal mucosa and the administration of RGE reduced the esophageal mucosa damage through the regulation of Nrf2 and NF-κB pathways. Our findings can considered as supplementary therapy in the prevention or treatment of reflux esophagitis.

상지에 배양한 상황버섯 균사체로부터 분리된 다당류의 면역증강 효과 (Immune-Enhancing Effects of Polysaccharides Isolated from Phellinus linteus Mycelium on Mori ramulus)

  • 박혜미;홍주헌
    • 한국식품영양과학회지
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    • 제46권1호
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    • pp.26-33
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    • 2017
  • 본 연구에서는 상지에 배양한 상황버섯 균사체 유래 다당류의 기능성 식품 소재로의 활용 가능성을 확인하기 위해 조다당류의 분리 및 정제를 통해 분획을 얻었으며, 다양한 면역증강 효과를 확인하였다. 건조된 조다당류를 DEAE-sepharose CL-6B를 이용하여 크로마토그래피한 후 340 nm에서의 흡광도, 단백질, 당 및 uronic acid 함량을 분석한 결과, 증류수로 용출되는 비흡착 분획(PF-1, 분획번호 3~15)과 흡착된 후 NaCl 용액에 의해 용출되는 분획(PF-2, 분획번호 24~33)을 얻었다. 분획물 PF-1 및 PF-2의 유용성분 함량으로 총당 함량은 각각 75.51%, 52.38%, 총단백질 함량은 1.63%, 8.41%, uronic acid 함량은 17.53%, 15.04% 및 ${\beta}-glucan$ 함량은 28.33%, 25.04%로 나타났다. PF-1 및 PF-2에 대해 대식세포주에 처리하여 세포생존율을 확인한 결과 $100{\mu}g/mL$ 농도까지 유의적으로 세포사멸이 나타나지 않아 세포독성이 없음을 확인할 수 있었다. Nitric oxide 생성량은 PF-1 $100{\mu}g/mL$에서는 nitric oxide 생성량이 $23.11{\mu}M$로 나타나 양성대조군으로 사용된 LPS 100 ng/mL 처리군($30.30{\mu}M$)의 약 76%의 효과가 있는 것으로 확인되었으며, cytokine 생성량($TNF-{\alpha}$ 및 IL-6) 또한 무처리군에 비하여 높은 생성량을 나타내었다. Polymerase chain reaction을 통한 면역 관련 유전자 발현분석 결과, iNOS, COX-2, $TNF-{\alpha}$, IL-6에서 PF-1 분획에서 높은 발현량을 나타내어 면역 증강을 목적으로 한 기능성 식품 개발에 활용 가능하다고 판단된다.

별불가사리 추출물의 면역세포 활성화 효과 (Effect of Asterina pectinifera Extracts on the Activation of Immune Cells)

  • 채수연;김미정;김도순;박정은;조성기;이성태
    • 한국식품영양과학회지
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    • 제36권3호
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    • pp.269-275
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    • 2007
  • 불가사리 추출물을 이용하여 생쥐 비장에 있는 면역세포 활성화 효과에 대해 실험한 결과, 다음과 같은 결과를 얻었다. 첫째, 별불가사리 추출물 중에서 B세포와 대식세포를 활성화시키는 성분은 아세톤처리로 추출할 수 있었다. 둘째, 이 성분은 농도 의존적으로 생쥐 비장세포의 증식반응을 유도하였으며, IL-6와 $IFN-{\gamma}$의 생산을 유도하였다. 셋째, 이 성분은 B세포의 증식을 유도하였으며, 이 때 면역글로불린 IgM과 IgG의 생산도 유도하였다. 넷째, 이 성분은 대식세포주의 일산화질소 생산을 유도하였으며, 또 $TNF-{\alpha}$, GM- CSF와 IL-6의 분비를 유도하였다. 이상의 실험 결과, 본 실험에서 사용한 별불가사리 추출물에는 B세포와 대식세포 같은 면역세포의 증식과 각종 사이토카인을 생산을 유도하여, 면역반응을 조절하는 성분이 포함되어 있는 것으로 생각된다.

노루궁뎅이버섯 균사체로 발효한 민들레잎 추출물의 항염증 활성 (Anti-Inflammatory Activities of Extracts from Fermented Taraxacum platycarpum D. Leaves Using Hericium erinaceum Mycelia)

  • 김연숙;정미연;유범석;박표잠;정재현
    • 한국식품영양과학회지
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    • 제45권1호
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    • pp.20-26
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    • 2016
  • 본 연구는 민들레잎을 노루궁뎅이버섯 균사체로 발효한 후물과 에탄올로 추출하여 추출용매별 및 발효 전과 발효 후의 항산화 및 항염증 활성을 비교 평가하였다. 추출물의 항산화 활성을 탐색하고자 총 폴리페놀 함량, 총 플라보노이드 함량, DPPH 라디칼 소거능, ABTS를 이용한 라디칼 소거 활성, FRAP을 이용한 총 항산화능을 측정하였다. 또한 RAW 264.7 대식세포를 이용하여 NO 생성량, 염증관련 단백질 및 사이토카인의 변화를 측정하였다. 민들레잎을 발효한 후 항산화 활성은 감소하였으나 오히려 항염증 활성은 증가하는 경향을 나타내었다. 특히 발효 민들레잎의 에탄올 추출물은 NO 생성 및 iNOS 단백질 발현을 효과적으로 억제하였으며 염증성 사이토카인인 IL-6를 억제하는 효과가 우수하였다. 이상의 결과로 항염증 소재로서 노루궁뎅이버섯 균사체를 이용한 발효 민들레잎의 에탄올 추출물의 활용 가능성을 확인하였다.

카드뮴으로 유발된 산화적 스트레스에 대한 침 자극의 간 보호 효과 (The Protective Effects of Acupuncture on the Liver in the Oxidative Stress Caused by Cadmium)

  • 신화영;이현종;임성철;이윤규;이봉효;정태영;김재수
    • Journal of Acupuncture Research
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    • 제31권4호
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    • pp.33-43
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    • 2014
  • This study was performed to investigate the protective effects of acupuncture on the liver in the oxidative stress caused by cadmium accumulation. Sprague-Dawley male($150{\pm}30g$) rats were stabilized for a week and divided into 5 groups which is normal, control, $LR_3$ acupuncture, $BL_{23}$ acupuncture and sham acupuncture group. For three days experimental groups were received oral doses of cadmium 2 mg/kg twice a day. Acupuncture was given bilaterally at each point 10 times for two weeks. The depth of stimulation was 1 mm at right angles and torsion of acupuncture was produced 2 times per second for 1 minutes. The liver was shipped off and taken weight at the last day of two weeks, and hepatic functions was confirmed through alanine transaminase(ALT) and aspartate amino-transferase(AST). We measured reactive oxygen species of serum, liver and kidney, and compared expression levels of superoxide dismutase(SOD), catalase, glutathione peroxidase(Gpx), nuclear factor erythroid derived 2-related factor 2(Nrf-2), heme oxygenase-1(HO-1), nuclear factor-${\kappa}B$ (NF-${\kappa}B$), cyclooxygenase-2(COX-2), inducible nitric oxide synthase(iNOS), Bax and Cytochrome c. $BL_{23}$ acupuncture group significantly increased liver weight and decreased ALT compared to control group. For the oxidative stress, $LR_3$ acupuncture group significantly reduced reactive oxygen species, and $BL_{23}$ acupuncture group significantly reduced reactive oxygen species and inflammation-related protein compared to control group. But $LR_3$ acupuncture group and $BL_{23}$ acupuncture group didn't significantly reduce apoptosis-related protein. Therefore $LR_3$ and $BL_{23}$ acupuncture showed the effects of antioxidant and anti-inflammatory, especially $BL_{23}$ acupuncture was more effective than $LR_3$ acupuncture on the protection of liver in the oxidative stress.

치매병태(癡呆病態)모델에서 천마(天麻)의 신경세포(神經細胞) 손상(損傷) 보호효과(保護效果) (Protective Effect of Gastrodia Elata on Neuronal Cell Damage in Alzheimer's Disease)

  • 정영수;강재현;박세환;권영미;김근우;구병수
    • 동의신경정신과학회지
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    • 제21권2호
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    • pp.125-140
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    • 2010
  • Objectives : The purpose of this study is to examine from various angles the protective effect of Gastrodia elata Blume (GEB) against nerve cell death induced by $\beta$-amyloid by using the cell line SH-SY5Y, which is commonly utilized for toxicity testing in nerve cells, and to find out its mechanism of action. Methods : To begin with, as a result of assessing the rate of cell survival by employing MTT reduction assay, the treatment with $\beta$-amyloid at different concentrations caused cytotoxicity, which was inhibited by preprocessing GEB extract. In addition, after $\beta$-amyloid was processed with the cell SH-SY5Y, apoptosis progressed, which was reduced effectively by processing GEB extract. Results : When cytotoxicity was caused by using hydrogen peroxide, a representative ROS, in order to examine the antioxidant effect of GEB, its protective effect was also observed. Apart from ROS, reactive nitrogen species (RNS) are also known to play a crucial role in nerve cell death. The treatment with the NO donor SNAP increased the production of nitric oxide and the expression of iNOS, which was also inhibited by GEB extract. Meanwhile, as an attempt to find out the mechanism of action explaining the antioxidant effect, the intracellular antioxidant enzyme expressions were measured by RT-PCR, which showed that GEB extract increased the expressions of heme oxygenase-1, GAPDH and $\gamma$-glutamate cysteine ligase. Lastly, GEB extract had a protective effect against impaired memory induced by scopolamine in animal models (in vivo). Conclusions : These findings indicate that GEB has a protective effect against the death of cranial nerve cells, suggesting possibilities for the prevention and treatment of AD.