• Title/Summary/Keyword: tumor necrosis factor-kappaB

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Anti-inflammatory Effect of MeOH Extracts of the Stem of Polygonum multiflorum in LPS-stimulated Mouse Peritoneal Macrophages

  • Cha, Dong-Seok;Jeon, Hoon
    • Natural Product Sciences
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    • v.15 no.2
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    • pp.83-89
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    • 2009
  • Polygoni multiflori Ramulus (PM), the stem of Polygonum multiflorum Thunb. has been widely used as a traditional medicine for the treatment of lots of diseases. In macrophages, nitric oxide is released as an inflammatory mediator and has been proposed to be an important modulator of many pathophysiological conditions in inflammation. In the present study, it was investigated that the inhibitory effects on NO and proinflammatory cytokines such as tumor necrosis factor alpha (TNF-${\alpha}$), interleukin-6 (IL-6) and the mechanism of down-regulation of immune response by 85% methanol extracts of PM in mouse (C57BL/6) peritoneal macrophages. Extracts of PM (0.1, 1 mg/ml) suppressed NO production and showed inhibition of proinflammatory cytokines like TNF-${\alpha}$, IL-6 and it attenuated iNOS and COX-2 expression via down-regulation of NF-${\kappa}$B activation. The present results indicate that the 85% methanol extracts of PM has an inhibitory effect on the production of NO through down-regulation of iNOS expression in LPS stimulated mouse peritoneal macrophages and therefore may be beneficial in diseases which related to macrophage-mediated inflammatory disorders.

Chemical Constituents Identified from Fruit Body of Cordyceps bassiana and Their Anti-Inflammatory Activity

  • Suh, Wonse;Nam, Gyeongsug;Yang, Woo Seok;Sung, Gi-Ho;Shim, Sang Hee;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • v.25 no.2
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    • pp.165-170
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    • 2017
  • Cordyceps bassiana is one of Cordyceps species with anti-oxidative, anti-cancer, anti-inflammatory, anti-diabetic, anti-obesity, anti-angiogenic, and anti-nociceptive activities. This mushroom has recently demonstrated to have an ability to reduce 2,4-dinitrofluorobenzene-induced atopic dermatitis symptoms in NC/Nga mice. In this study, we further examined phytochemical properties of this mushroom by column chromatography and HPLC analysis. By chromatographic separation and spectroscopic analysis, 8 compounds, such as 1,9-dimethylguanine (1), adenosine (2), uridine (3), nicotinamide (4), 3-methyluracil (5), 1,7-dimethylxanthine (6), nudifloric acid (7), and mannitol (8) were identified from 6 different fractions and 4 more subfractions. Through evaluation of their anti-inflammatory activities using reporter gene assay and mRNA analysis, compound 1 was found to block luciferase activity induced by $NF-{\kappa}B$ and AP-1, suppress the mRNA levels of cyclooxygenase (COX)-2 and tumor necrosis factor $(TNF)-{\alpha}$. Therefore, our data strongly suggests that compound 1 acts as one of major principles in Cordyceps bassiana with anti-inflammatory and anti-atopic dermatitis activities.

Investigation of Immunostimulatory Effects of Heat-Treated Lactiplantibacillus plantarum LM1004 and Its Underlying Molecular Mechanism

  • Bae, Won-Young;Jung, Woo-Hyun;Shin, So Lim;Kwon, Seulgi;Sohn, Minn;Kim, Tae-Rahk
    • Food Science of Animal Resources
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    • v.42 no.6
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    • pp.1031-1045
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    • 2022
  • Postbiotics are defined as probiotics inactivated by heat, ultraviolet radiation, sonication, and other physical or chemical stresses. Postbiotics are more stable than probiotics, and these properties are advantageous for food additives and pharmacological agents. This study investigated the immunostimulatory effects of heat-treated Lactiplantibacillus plantarum LM1004 (HT-LM1004). Cellular fatty acid composition of L. plantarum LM1004 isolated form kimchi was analyzed by gas chromatography-mass spectrometry detection system. The nitric oxide (NO) content was estimated using Griess reagent. Immunostimulatory cytokines were evaluated using enzyme-linked immunosorbent assay. Relative protein expressions were evaluated by western blotting. Phagocytosis was measured using enzyme-labelled Escherichia coli particles. L. plantarum LM1004 showed 7 kinds of cellular fatty acids including palmitic acid (C16:0). The HT-LM1004 induced release of NO and upregulated the inducible NO synthase in RAW 264.7 macrophage cells. Tumor necrosis factor-α and interleukin-6 levels were also increased compared to control (non-treated macrophages). Furthermore, HT-LM1004 modulated mitogen-activated protein kinase (MAPK) subfamilies including p38 MAPK, extracellular signal-regulated kinase 1/2, and c-Jun N-terminal kinase. Therefore, these immunostimulatory effects were attributed to the production of transcriptional factors, such as nuclear factor kappa B (NF-κB) and the activator protein 1 family (AP-1). However, HT-LM1004 did not showed significant phagocytosis of RAW 264.7 macrophage cells. Overall, HT-LM1004 stimulated MAPK/AP-1 and NF-κB expression, resulting in the release of NO and cytokines. These results will contribute to the development of diverse types of food and pharmacological products for immunostimulatory agents with postbiotics.

Vibrio Vulnificus Induces the Inflammation of Mouse Ileal Epithelium: Involvement of Protein Kinase C and Nuclear Factor-Kappa B (회장 상피세포에서 비브리오균(Vibrio vulnificus)의 염증 유도 기작 연구: protein kinase C와 nuclear factor kappa-B의 관련성)

  • Han, Gi Yeon;Jung, Young Hyun;Jang, Kyung Ku;Choi, Sang Ho;Lee, Sei-Jung
    • Journal of Life Science
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    • v.24 no.6
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    • pp.664-670
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    • 2014
  • In the present study, we investigate the role of V. vulnificus in promoting the inflammation of mouse ileal ephitelium and its related signaling pathways. ICR mice were infected orally with V. vulnificus ($1{\times}10^9CFU$) for 16 h as a representative model of food-borne infection. To find the major portal of entry of V. vulnificus in mouse intestine, we have measured the levels of bacterial colonization in small intestine, colon, spleen, and liver. V. vulnificus appeared to colonize in intestine and colon in the order of ileum >> jejunum> colon, but lack in the duodenum, spleen, and liver. V. vulnificus in ileum caused severe necrotizing enteritis and showed shortened villi heights accompanied by an expanded width and inflammation, compared with the control mice. V. vulnificus induced ileal epithelium inflammation by activating phosphorylation of PKC and membrane translocation of $PKC{\alpha}$. V. vulnificus induced the phosphorylation of ERK and JNK, but did not affect p38 MAPK phosphorylation. Notably, V. vulnificus stimulated the I-${\kappa}B$-dependent phosphorylation of NF-${\kappa}B$ in mouse ileal epithelium. Finally, the ileal infection of V. vulnificus resulted in a significant increase in expression of proinflammatory cytokines and Toll-like receptors, respectively, compared to the control. Collectively, our results indicate that V. vulnificus induces ileal epithelium inflammation by increasing NF-${\kappa}B$ phosphorylation via activation of PKC, ERK, and JNK, which is critical for host defense mechanism in food-borne infection by V. vulnificus.

Diallyl Disulfide Prevents Cyclophosphamide-Induced Hemorrhagic Cystitis in Rats through the Inhibition of Oxidative Damage, MAPKs, and NF-κB Pathways

  • Kim, Sung Hwan;Lee, In Chul;Ko, Je Won;Moon, Changjong;Kim, Sung Ho;Shin, In Sik;Seo, Young Won;Kim, Hyoung Chin;Kim, Jong Choon
    • Biomolecules & Therapeutics
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    • v.23 no.2
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    • pp.180-188
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    • 2015
  • This study investigated the possible effects and molecular mechanisms of diallyl disulfide (DADS) against cyclophosphamide (CP)-induced hemorrhagic cystitis (HC) in rats. Inflammation response was assessed by histopathology and serum cytokines levels. We determined the protein expressions of nuclear transcription factor kappa-B (NF-${\kappa}B$), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), oxidative stress, urinary nitrite-nitrate, malondialdehyde (MDA), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Finally, we studied the involvement of mitogen-activated protein kinases (MAPKs) signaling in the protective effects of DADS against CP-induced HC. CP treatment caused a HC which was evidenced by an increase in histopathological changes, proinflammatory cytokines levels, urinary nitrite-nitrate level, and the protein expression of NF-${\kappa}B$, COX-2, iNOS, TNF-${\alpha}$, p-c-Jun N-terminal kinase (JNK), and p-extracellular signal regulated kinase (ERK). The significant decreases in glutathione content and glutathione-S-transferase and glutathione reductase activities, and the significant increase in MDA content and urinary MDA and 8-OHdG levels indicated that CP-induced bladder injury was mediated through oxidative DNA damage. In contrast, DADS pretreatment attenuated CP-induced HC, including histopathological lesion, serum cytokines levels, oxidative damage, and urinary oxidative DNA damage. DADS also caused significantly decreased the protein expressions of NF-${\kappa}B$, COX-2, iNOS, TNF-${\alpha}$, p-JNK, and p-ERK. These results indicate that DADS prevents CP-induced HC and that the protective effects of DADS may be due to its ability to regulate proinflammatory cytokines production by inhibition of NF-${\kappa}B$ and MAPKs expressions, and its potent anti-oxidative capability through reduction of oxidative DNA damage in the bladder.

Antioxidant Activity and Anti-inflammatory Effect of Extracts from Paulownia tomentosa in LPS-stimulated RAW264.7 macrophage cells

  • Jo, Na-Young;Kim, Ki-Tae
    • The Journal of Korean Medicine
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    • v.40 no.4
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    • pp.72-83
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    • 2019
  • In this study, we investigated the antioxidant and anti-inflammatory effect of the Paulownia tomentosa extracts (PTE). The total polyphenol and flavonoid contents of PTE were 148.98±1.84 mg GAE/g extract, and 115.33±4.16 mg CE/g extract, respectively. The PTE showed that strong antioxidant activity via -diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, ABTS radical scavenging activity and FRAP assay. The anti-inflammatory activity was evaluated on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. PTE remarkably reduced protein expression of inducible nitric oxide (iNOS), resulting in inhibition of production of nitric oxide (NO). Additionally, pre-treatment of PTE significantly suppressed the production of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Moreover, PTE significantly attenuated LPS-induced IkappaB (IκB) degradation and suppressed nuclear factor kappa B (NF-κB) nuclear translocation in macrophages. The PTE showed high antioxidant and anti-inflammatory activity. These data suggest that PTE has pharmacological activity and may be useful for the development of anti-inflammatory agents.

Cornuside inhibits glucose-induced proliferation and inflammatory response of mesangial cells

  • Xiaoxin Li;Lizhong Guo;Fei Huang;Wei Xu;Guiqing Peng
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.6
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    • pp.513-520
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    • 2023
  • Cornuside is a secoiridoid glucoside compound extracted from the fruits of Cornus officinalis. Cornuside has immunomodulatory and anti-inflammatory properties; however, its potential therapeutic effects on diabetic nephropathy (DN) have not been completely explored. In this study, we established an in vitro model of DN through treating mesangial cells (MMCs) with glucose. MMCs were then treated with different concentrations of cornuside (0, 5, 10, and 30 μM). Cell viability was determined using cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Levels of proinflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α, and IL-1β were examined using enzyme-linked immunosorbent assay. Reverse transcription quantitative real-time polymerase chain reaction and Western blotting were performed to detect the expression of AKT and nuclear factor-kappa B (NF-κB)-associated genes. We found that cornuside treatment significantly reduced glucose-induced increase in MMC viability and expression of pro-inflammatory cytokines. Moreover, cornuside inhibited glucose-induced phosphorylation of AKT and NF-κB inhibitor alpha, decreased the expression of proliferating cell nuclear antigen and cyclin D1, and increased the expression of p21. Our study indicates that the anti-inflammatory properties of cornuside in DN are due to AKT and NF-κB inactivation in MMCs.

The Effects of LR3 and SP6 Acupuncture on Liver Damage of Streptozotocin-induced Diabetic Mice (태충혈과 삼음교혈의 침 자극이 Streptozotocin으로 유발된 당뇨쥐의 간 손상에 미치는 영향)

  • Kim, Sung Jin;Lee, Yun Kyu;Lee, Hyun Jong;Kim, Jae Soo
    • Journal of Acupuncture Research
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    • v.33 no.3
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    • pp.29-43
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    • 2016
  • Objectives : The purpose of this study was to investigate the effect of LR3 and SP6 acupuncture on liver damage of streptozotocin-induced diabetic mice. Methods : Male ICR mice were divided into four groups, consisting of the normal mice group(N), acupuncture-free diabetic mice group(Con), LR3-acupuncture diabetic mice group(LR3) and SP6-acupuncture diabetic mice group(SP6). The following measurements were taken: Body weight, food intake and water intake for 2 weeks; liver weight, and glucose levels in the serum and liver; ALT and AST in the serum; reactive oxygen species(ROS), reduced glutathione(GSH) and oxidized glutathione(GSSG) in the liver; and lastly, receptor for advanced glycation endproducts( RAGE), $N{\varepsilon}-carboxymethyl$ lysine(CML), $N{\varepsilon}-carboxyethyl$ lysine(CEL), phosphorylation of inhibitory kappa B alpha($p-I{\kappa}B{\alpha}$), nuclear factor-kappa B($NF-{\kappa}B$), activator protein-1(AP-1), cyclooxygenase-2(COX-2), inducible nitric oxide synthase(iNOS), tumor necrosis factor-alpha($TNF-{\alpha}$), ${\beta}-actin$, cytochrome c and caspase in the liver. Results : The liver weight and GSH/GSSG ratio were significantly increased in SP6 compared to Con. The glucose levels in the liver were significantly decreased in LR3 compared to Con. The generation of ROS and GSSG were significantly decreased in SP6 compared to Con. The expressions of RAGE, CML, AP-1, $TNF-{\alpha}$, cytochrome c and caspase 3 were significantly decreased in LR3 compared to Con. The expressions of $p-I{\kappa}B{\alpha}$, $NF-{\kappa}B$, AP-1, COX-2, iNOS and caspase 3 were significantly decreased in SP6 compared to Con. Conclusion : It is predicted that LR3 acupuncture is related to reduced glucose levels in the liver and expressions of AGE, and that, SP6 acupuncture is related to reduced oxidative stress-related transcription factors and inflammation-related proteins. Therefore, we suggest that LR3 and SP6 acupuncture have protective effects on the liver of streptozotocin-induced diabetic mice by preventing apoptosis.

Anti-Inflammatory Effect of Hot Water Extract of Aronia Fruits in LPS-Stimulated RAW 264.7 Macrophages (LPS 자극 RAW 264.7 대식세포에 있어서 아로니아 열매 열수 추출물의 항염증 효과)

  • Yang, Hui;Oh, Kwang-Hoon;Yoo, Yung Choon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.1
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    • pp.7-13
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    • 2015
  • In this study, anti-inflammatory activity of hot water extract of Aronia fruits (AF-H) was examined. Pre-treatment with AF-H significantly inhibited production of nitric oxide (NO) and prostaglandin E-2 in a dose-dependent manner in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. The inhibitory effect of AF-H on LPS-induced inflammation was also confirmed by down-regulation of inducible NO synthase as well as cyclooxygenase-2 protein expression. Furthermore, treatment with AF-H significantly inhibited secretion of inflammatory cytokines such as tumor-necrosis $factor-{\alpha}$ and interleukin-6. Signal transduction pathway studies further indicated that AF-H inhibited LPS-induced activation of nuclear $factor-{\kappa}B$, but not mitogen-activated protein kinase. Treatment with AF-H also partially protected against LPS-induced lethal shock in C57BL/6 mice, although its effect was not statistically significant. These results suggest that AF-H is a more promising nutraceutical or medicinal agent for inhibition of LPS-induced inflammation or inflammation-related diseases.

Anti-Inflammatory Effect of Ethanol Extract from the Seeds of Arctium Lappa L. in Vascular Endothelial Cells (혈관내피세포에서 우방자(牛蒡子) 에탄올 추출물의 항염증 효과)

  • Lee, Yun-Jung;Yoon, Jung-Joo;Kim, Hye-Yoom;Ahn, You-Mee;Hong, Mi-Hyeon;Son, Chan-Ok;Na, Se-Won;Lee, Ho-Sub;Kang, Dae-Gill
    • The Journal of Korean Obstetrics and Gynecology
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    • v.32 no.3
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    • pp.20-31
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    • 2019
  • Objectives: The seeds from Arctium lappa have been considered for its various pharmacological properties, which include anti-carcinogenic, anti-inflammatory, anti-diabetic, and anti-viral activities. Methods: In the present study, we investigated the anti-inflammatory effect of the ethanol extract from the seeds of Arctium lappa L (EAL) on cytokine-induced vascular inflammation in human umbilical vein endothelial cells (HUVEC). Results: Pretreatment with EAL significantly decreased tumor necrosis factor alpha ($TNF-{\alpha}$)-induced cell adhesion molecules expression such as intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial-selectin (E-selectin) in a dose-dependent manner. Cell adhesion assay showed that pretreatment with EAL suppressed HUVEC-monocyte adhesion by $TNF-{\alpha}$ over $1{\mu}g/ml$ concentration. We investigated the involvement of nuclear transcription factor kappa-B ($NF-{\kappa}B$) in $TNF-{\alpha}$-induced vascular inflammation. $NF-{\kappa}B$ p65 nuclear expression was induced by $TNF-{\alpha}$, however, pretreatment with EAL was attenuated that nuclear translocation. In cytoplasm, EAL was also attenuated $TNF-{\alpha}$-induced decrease of inhibitor of ${\kappa}B-{\alpha}$ ($I{\kappa}B-{\alpha}$) expression. Moreover, EAL significantly decreased $TNF-{\alpha}$-induced production of intracellular reactive oxygen species (ROS). Conclusions: Taken together, our findings suggest that seeds of Arctium lappa L could be a therapeutic herb for prevention of cardiovascular diseases throughout the inhibition of vascular endothelial inflammation.