• Title/Summary/Keyword: NF-${\kappa}{\beta}$

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Can herbal drug(s) meet the challenges of genomewide screen results on rheumatoid arthritis

  • Paul, Bholanath
    • Advances in Traditional Medicine
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    • v.5 no.4
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    • pp.251-261
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    • 2005
  • Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. RA is characterized by chronic inflammation of the synovial membrane in the joint, which leads to the progressive destruction of articular cartilage, ligament and bone. Several cytokines such as tumor necrosis $factor-{\alpha}\;TNF-{\alpha}\;and\;interleukin-1{\beta}\;(IL-1{\beta})$ and interleukin-6 (IL-6) have been implicated in the pathological mechanisms of synovial tissue proliferation, joint destruction and programmed cell death in rheumatoid joint. Genome wide screening of subjects suffering from autoimmune diseases especially arthritis revealed linkage to inflammatory molecules like $TNF-{\alpha},\;IL-1{\beta}$ and IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nuclear factor-kappaB $(NF-{\kappa}B)$ and human leucocyte antigen/major histocompatibility complex (HLA/MHC) locus. The status of the pharmacological mechanism of herbal drugs in the light of genome wide screening results has been discussed to reinforce the therapeutic potential and the pharmacological basis of the herbal drugs.

Anti-Inflammatory Effect of Grateloupia imbricata Holmes Ethanol Extract on LPS-Induced RAW 264.7 Cells (꽃지누아리 에탄올 추출물의 LPS로 유도된 RAW 264.7 세포에 대한 항염증 효과)

  • Kim, Min-Ji;Bae, Nan-Yong;Kim, Koth-Bong-Woo-Ri;Park, Ji-Hye;Park, Sun-Hee;Choi, Jung-Su;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.2
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    • pp.181-187
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    • 2016
  • Algae is a potential resource with various biological activities. In this study, the anti-inflammatory effect of Grateloupia imbricata Holmes ethanol extract (GIHEE) from red algae was investigated in LPS-induced RAW 264.7 cells. As a result, reduced secretion of pro-inflammatory cytokines [tumor necrosis factors-${\alpha}$, interleukin (IL)-$1{\beta}$, and IL-6] and nitric oxide (NO) was observed in a dose-dependent manner. Expression of nuclear factor-kappaB (NF-${\kappa}B$) as well as inducible NO synthase and cyclooxygenase-2 proteins was reduced by GIHEE, suggesting that the anti-inflammatory activity of GIHEE is related to suppression of NF-${\kappa}B$ signaling pathways. In addition, GIHEE reduced phosphorylation of mitogen-activated protein kinases. These results suggest that GIHEE can be used as a potential anti-inflammatory therapeutic.

Anti-inflammatory effects of Herba Artemisiae Capillaris as a consequence of the inhibition of NF-kappa B-dependent iNOS and pro-inflammatory cytokines production. (Nuclear Factor kappa B 억제를 통한 인진추출물의 inducible Nitric Oxide synthase 및 Cytokine 억제효과)

  • Kim, Dae-Sung;Park, Sook-Jahr;Jo, Mi-Jeong;Park, Sang-Mi;Kim, Sang-Chan;Byun, Sung-Hui
    • Herbal Formula Science
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    • v.17 no.2
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    • pp.151-162
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    • 2009
  • Herba Artemisiae Capillaris is the dried bud of Artemisia capillaris Thunb, which has been used for expelling heat to loosen the bowels and normalizing gallbladder function to cure jaundice in traditional oriental medicines. In the present study, we evaluated the anti-inflammatory effects of the aqueous extracts of Herba Artemisiae Capillaris (HAC) in LPS-activated Raw 264.7 cells. Cells were treated with $1\;{\mu}g/ml$ of LPS 1 h before adding HAC extract. Cell viability was determined by MTT assay, and the relative level of NO was measured with Griess reagent. TNF-$\alpha$, IL-$1{\beta}$, and IL-6 cytokines were detected by ELISA. During the entire experimental period, all three doses of HAC extract (0.03, 0.10 and 0.30 mg/ml) had no significant cytotoxicity. LPS-activated cells showed increased NO levels and iNOS expressions compared to control. However, these increases were dramatically attenuated by treatment with HAC extract. Moreover, the inhibitory effects of HAC extract occurred in a dose-dependent manner. In addition, HAC extract reduced the translocation of $NF{\kappa}B$ into nuclear. HAC reduced production of IL-$1{\beta}$ and IL-6 by LPS, although it had no effects on TNF-$\alpha$. These results demonstrate that liquiritigenin exerts anti-inflammatory effects, which results from the inhibition of $NF{\kappa}B$ activation in macrophages, thereby decreasing production of iNOS and proinflammatory cytokines. Taken together, these results indicate that the aqueous extracts of Herba Artemisiae Capillaris warrant further development as an anti-inflammatory agent for the treatment of gram-negative bacterial infections.

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Photoprotective Potential of Penta-O-Galloyl-β-D-Glucose by Targeting NF-κB and MAPK Signaling in UVB Radiation-Induced Human Dermal Fibroblasts and Mouse Skin

  • Kim, Byung-Hak;Choi, Mi Sun;Lee, Hyun Gyu;Lee, Song-Hee;Noh, Kum Hee;Kwon, Sunho;Jeong, Ae Jin;Lee, Haeri;Yi, Eun Hee;Park, Jung Youl;Lee, Jintae;Joo, Eun Young;Ye, Sang-Kyu
    • Molecules and Cells
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    • v.38 no.11
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    • pp.982-990
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    • 2015
  • Exposure of the skin to ultraviolet radiation can cause skin damage with various pathological changes including inflammation. In the present study, we identified the skin-protective activity of 1,2,3,4,6-penta-O-galloyl-${\beta}$-D-glucose (pentagalloyl glucose, PGG) in ultraviolet B (UVB) radiation-induced human dermal fibroblasts and mouse skin. PGG exhibited antioxidant activity with regard to intracellular reactive oxygen species (ROS) generation as well as ROS and reactive nitrogen species (RNS) scavenging. Furthermore, PGG exhibited anti-inflammatory activity, inhibiting the activation of nuclear factor-kappaB (NF-${\kappa}B$) and mitogen-activated protein kinase (MAPK) signaling, resulting in inhibition of the expression of pro-inflammatory mediators. Topical application of PGG followed by chronic exposure to UVB radiation in the dorsal skin of hairless mice resulted in a significant decrease in the progression of inflammatory skin damages, leading to inhibited activation of NF-${\kappa}B$ signaling and expression of pro-inflammatory mediators. The present study demonstrated that PGG protected from skin damage induced by UVB radiation, and thus, may be a potential candidate for the prevention of environmental stimuli-induced inflammatory skin damage.

Glycated Serum Albumin Induces Interleukin-6 Expression in Vascular Smooth Muscle Cells (혈관평활근세포에서 glycated albumin에 의한 interleukin-6 증가에 관여하는 인자에 대한 연구)

  • Baek, Seung-Il;Rhim, Byung-Yong;Kim, Koan-Hoi
    • Journal of Life Science
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    • v.21 no.1
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    • pp.36-43
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    • 2011
  • Diabetes mellitus is associated with vascular complications. Diabetic patients exhibit high levels of glycated adducts in serum compared to non-diabetic individuals. The aim of this study was to investigate whether extracellular glycated albumin (GA) predisposes vascular smooth muscle cells (VSMCs) to pro-inflammatory phenotype. Exposure of rat aortic smooth muscle cells (AoSMCs) to GA not only enhanced interleukin-6 (IL-6) release but also activated promoter activity of the IL-6 gene. GA-induced IL-6 promoter activation was suppressed by dominant-negative forms of Toll-like receptor (TLR)-4 and myeloid differentiation factor 88 (MyD88), but not by dominant-negative-forms of TLR-2 and TIR-domain-containing adapter-inducing interferon-$\beta$ (TRIF). Extracellular signal-regulated kinase (ERK) inhibition and diphenyleneiodium (DPI) also attenuated IL-6 induction by GA. Mutation at the nuclear factor-${\kappa}B$ (NF-${\kappa}B$)-binding site in the IL-6 promoter region suppressed promoter activation in response to GA. The present study proposes that GA would contribute to inflammatory reaction in the stressed vasculature by inducing IL-6 in VSMCs, and that TLR-4, EKR, and NF-${\kappa}B$ play active roles in the process.

Mechanism Underlying the Anti-Inflammatory Action of Piceatannol Induced by Lipopolysaccharide (당지질로 유도한 염증반응에서 Piceatannol의 항염증 기전 연구)

  • Cho, Han-Jin;Shim, Jae-Hoon;So, Hong-Seob;YoonPark, Jung-Han
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.41 no.9
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    • pp.1226-1234
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    • 2012
  • 3,4,3',5'-Tetrahydroxy-trans-stilbene (piceatannol) is a derivative of resveratrol with a variety of biological activities, including anti-inflammatory, anti-proliferative, and anti-cancer activities. We assessed the mechanisms by which piceatannol inhibits inflammatory responses using lipopolysaccharide (LPS)-treated Raw264.7 murine macrophages. Piceatannol (0~10 ${\mu}mol/L$) decreased LPS-induced release of nitric oxide, tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, IL-$1{\beta}$, and inhibited LPS-induced protein expression of inducible nitric oxide synthase (iNOS). Activation of nuclear factor-kappaB (NF-${\kappa}B$), activator protein (AP)-1, and signal transducer and activator of transcription 3 (STAT3) are crucial steps during an inflammatory response. Piceatannol prevented LPS-induced degradation of inhibitor of ${\kappa}B$ ($I{\kappa}B$), translocation of p65 to the nucleus, and phosphorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (SAPK/JNK). Additionally, piceatannol inhibited LPS-induced phosphorylation of STAT3 and IL-6-induced translocation of STAT3 to the nucleus. Furthermore, piceatannol increased the protein and mRNA levels of hemeoxygenase (HO)-1, the rate-limiting enzyme of heme catabolism that plays a critical role in mediating antioxidant and anti-inflammatory effects. Piceatannol further induced antioxidant response elements (ARE)-driven luciferase activity in Raw264.7 cells transfected with an ARE-luciferase reporter construct containing the enhancer 2 and minimal promoter region of HO-1. These results suggest that piceatannol exerts anti-inflammatory effects via the down-regulation of iNOS expression and up-regulation of HO-1 expression.

Anti-inflammatory Activities of an Ethanol Extract of Sargassum macrocarpum in Lipopolysaccharide (LPS)-stimulated RAW 264.7 Macrophages (Lipopolysaccaride로 유도된 Raw 264.7 세포에서 큰열매모자반 에탄올 추출물의 항염증 활성)

  • Cheon, Ji Min;Kim, Hyang Suk;Choi, Eun Ok;Kwon, Da Hye;Choi, Yung Hyun;Kim, Byung Woo;Hwang, Hye Jin
    • Journal of Life Science
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    • v.27 no.12
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    • pp.1437-1444
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    • 2017
  • Sargassum macrocarpum is a widely distributed marine brown algae found in the North Pacific. The objective of this study was to evaluate the anti-inflammatory activity of an ethanol extract of S. macrocarpum (EESM). First, we investigated the anti-inflammatory activities of EESM in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. EESM treatment suppressed nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production and inhibited the expressions of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at the mRNA and protein levels. In addition, the expression of pro-inflammatory cytokines, such as tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and interleukin-1 beta ($IL-1{\beta}$), was decreased in a dose dependent manner. Investigation of the signaling pathways of nuclear factor kappa B ($NF-{\kappa}B$), phosphoinositide-3-kinase (PI3K)/Akt, and mitogen-activated protein kinases (MAPKs) revealed suppression of $NF-{\kappa}B$ translocation from the cytosol to nucleus by EESM treatment. The phosphorylation of the Akt and ERK proteins was also inhibited by EESM treatment. EESM treatment also stimulated the expression of the heme oxygenase-1 (HO-1) enzyme and its upstream transcription factor, nuclear factor-E2-related factor 2 (Nrf2). These results suggest that EESM has anti-inflammatory activity and could have potential uses in the field of nutraceuticals.

Anti-Inflammatory Effect of Fermented Liriope platyphylla Extract in LPS-stimulated RAW 264.7 Macrophages

  • Lee, Hyun-Ah;Han, Ji-Sook
    • Preventive Nutrition and Food Science
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    • v.16 no.4
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    • pp.299-306
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    • 2011
  • The present study was designed to evaluate the inhibitory effects of fermented Liriope platyphylla extract on the production of inflammation-related mediators (NO, ROS, NF-${\kappa}B$, iNOS and COX-2) and pro-inflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6) in lipopolysaccharide-stimulated RAW 264.7 macrophages. Freeze-dried Liriope platyphylla was fermented by Saccharomyces cerevisiae and extracted with 70% ethanol. In lipopolysaccharide-stimulated macrophage cells, the treatment with fermented Liriope platyphylla extract decreased the generation of intracellular reactive oxygen species dose-dependently and increased antioxidant enzyme activities, including superoxide dismutase, catalase and glutathione peroxidase. Fermented Liriope platyphylla extract also inhibited NO production in lipopolysaccharide-stimulated RAW 264.7 cell. The expressions of NF-${\kappa}B$, iNOS, COX-2 and pro-inflammatory cytokines were inhibited by the treatment with fermented Liriope platyphylla extract. Thus, this study shows the fermented Liriope platyphylla extract could be effective at inhibiting the inflammation process.

Suppressive Effects of Fucoxanthin on Degranulation in IgE-antigen complex-stimulated RBL-2H3 Cells

  • NamKoong, Seung;Joo, Hae-Mi;Jang, Seon-A;Kim, Ye-Jin;Kim, Tae-Seong;Sohn, Eun-Hwa
    • Korean Journal of Plant Resources
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    • v.25 no.3
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    • pp.339-345
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    • 2012
  • The marine carotenoid fucoxanthin can be found in marine brown seaweeds, macroalgae, diatoms, and microalgae, and has remarkable biological properties. Numerous studies have shown that fucoxanthin has considerable potential and promising applications in human health, but the underlying mechanisms involved in its anti-allergic activity are not fully understood. We here investigated the mechanisms by anti-allergic activity of fucoxanthin fraction from Eisenia bicyclis in immunoglobulin E-antigen complex (IgE/DNP-BSA)-stimulated RBL-2H3 mast cells. This study we found that the fucoxanthin inhibits the release of ${\beta}$-hexosaminidase and suppressed not only transcriptional activation of NF-${\kappa}B$, but also phosphorylation of ERK and JNK in IgE/DNP-BSA-treated RBL-2H3 cells. Fucoxanthin may be useful for preventing allergic diseases, including asthma and atopic dermatitis.