• Title/Summary/Keyword: anti-inflammatory$NF-{\kappa}B$

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Inhibitory Effect of Sageretia theezans against the Production of Pro-Inflammatory Mediators through the Inhibition of NF-κB and MAPK, and Activation of Nrf2/HO-1 Signaling Pathways in LPS-Stimulated RAW264.7 cells

  • Kim, Ha Na;Park, Su Bin;Kim, Jeong Dong;Jeong, Hyung Jin;Jeong, Jin Boo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.10a
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    • pp.98-98
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    • 2018
  • In this study, we evaluated the anti-inflammatory effect of extracts of leaves (ST-L) and branches (ST-B) from Sageretia theezans in LPS-stimulated RAW264.7 cells. ST-L and ST-B significantly inhibited the production of the pro-inflammatory mediators such as NO, iNOS, COX-2, $IL-1{\beta}$ and IL-6 in LPS-stimulated RAW264.7 cells. ST-L and ST-B blocked LPS-induced degradation of $I{\kappa}B-{\alpha}$ and nuclear accumulation of p65, which resulted to the inhibition of $NF-{\kappa}B$ activation in RAW264.7 cells. ST-L and ST-B also attenuated the phosphorylation of ERK1/2, p38 and JNK in LPS-stimulated RAW264.7 cells. In addition, ST-L and ST-B increased HO-1 expression in RAW264.7 cells, and the inhibition of HO-1 by ZnPP reduced the inhibitory effect of ST-L and ST-B against LPS-induced NO production in RAW264.7 cells. Inhibition of p38 activation and ROS elimination attenuated HO-1 expression by ST-L and ST-B, and ROS elimination inhibited p38 activation induced by ST-L and ST-B. ST-L and ST-B dramatically induced nuclear accumulation of Nrf2, but this was significantly reversed by the inhibition of p38 activation and ROS elimination. Collectively, our results suggest that ST-L and ST-B exerts potential anti-inflammatory activity by suppressing $NF-{\kappa}B$ and MAPK signaling activation, and activating HO-1 expression through the nuclear accumulation of Nrf2 via ROS-dependent p38 activation. These findings suggest that ST-L and ST-B may have great potential for the development of anti-inflammatory drug to treat acute and chronic inflammatory disorders.

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Magnolol Inhibits LPS-induced NF-${\kappa}B$/Rel Activation by Blocking p38 Kinase in Murine Macrophages

  • Li, Mei Hong;Kothandan, Gugan;Cho, Seung-Joo;Huong, Pham Thi Thu;Nan, Yong Hai;Lee, Kun-Yeong;Shin, Song-Yub;Yea, Sung-Su;Jeon, Young-Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.14 no.6
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    • pp.353-358
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    • 2010
  • This study demonstrates the ability of magnolol, a hydroxylated biphenyl compound isolated from Magnolia officinalis, to inhibit LPS-induced expression of iNOS gene and activation of NF-${\kappa}B$/Rel in RAW 264.7 cells. Immunohisto-chemical staining of iNOS and Western blot analysis showed magnolol to inhibit iNOS gene expression. Reporter gene assay and electrophoretic mobility shift assay showed that magnolol inhibited NF-${\kappa}B$/Rel transcriptional activation and DNA binding, respectively. Since p38 is important in the regulation of iNOS gene expression, we investigated the possibility that magnolol to target p38 for its anti-inflammatory effects. A molecular modeling study proposed a binding position for magnolol that targets the ATP binding site of p38 kinase (3GC7). Direct interaction of magnolol and p38 was further confirmed by pull down assay using magnolol conjugated to Sepharose 4B beads. The specific p38 inhibitor SB203580 abrogated the LPS-induced NF-${\kappa}B$/Rel activation, whereas the selective MEK-1 inhibitor PD98059 did not affect the NF-${\kappa}B$/Rel. Collectively, the results of the series of experiments indicate that magnolol inhibits iNOS gene expression by blocking NF-${\kappa}B$/Rel and p38 kinase signaling.

Anti-inflammatory effects of the water extract of Ecliptae Herba (한련초(旱蓮草) 추출물의 항염증 효과)

  • Jo, Hee-Chang;Jung, Ho-Jun;Kim, Sang-Chan;Jee, Seon-Young
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.23 no.2
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    • pp.125-138
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    • 2010
  • Objective : The present study was examined to evaluate the effects of Ecliptae Herba on the production of inflammatory mediators in vivo and in vitro. Methods : In cell viability, all three doses of Ecliptae Herba extract (25, 50 and $100\;{\mu}g/ml$) had no significant cytotoxicity during the experimental period. The increases of NO production and iNOS expression were detected in LPS-activated cells compared to control, but these increases were dose-dependently attenuated by pre-treatment with Ecliptae Herba extract. Results : 1. LPS plays a pivotal roles in inducing to the massive production of pro-inflammatory cytokines such as TNF-$\alpha$, IL-$1{\beta}$ and IL-6 in macrophages. 2. Ecliptae Herba extract reduced the elevated production of cytokines by LPS. 3. Ecliptae Herba extract reduced $PGE_2$ levels in a dose-dependent manner as a consequence of inhibition of COX-2 activity. 4. Ecliptae Herba extract significantly reduced the nuclear translocation of $NF-{\kappa}B$ induced by LPS. 5. In histopathological study, Ecliptae Herba effectively inhibited the increases of hind paw edema, skin thicknesses and inflammatory cell infiltrations induced by carrageenan treatment. Conclusions : These results provide evidences that therapeutic effect of Ecliptae Herba on the acute inflammation is partly due to the reduction of some of inflammatory factors by inhibiting iNOS and COX-2 through the suppression of $NF-{\kappa}B$.

Recent Prospect of Compounds Derived from Marine Macroalgae for Medicinal Application of Anti-Inflammation for Chemoprevention of Cancer

  • Kim, Moon-Moo
    • Journal of Marine Bioscience and Biotechnology
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    • v.5 no.4
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    • pp.8-14
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    • 2011
  • Although marine living organism contains a numerious number of compounds, it is difficult to collect these compounds in a large scale for medicinal application. However, in recent years, several bioactive compounds isolated from marine macroalgae have been proved to be able to provide potential sources for development of medicinal products because they can be obtained in large amount from marine. A number of studies have reported a variety of effects of marine macroalgae but a few anti-inflammatory activity of marine macroalgae have recently been published. Herein, we reviewed novel anti-inflammatory compounds recently isolated from marine brown algae, green algae and red algae. From this survey, in particular, some compounds contained in edible macroalgae exert anti-inflammatory effects with inhibition on cyclooxygenase-2 (COX-2), inducible nitric oxide synthase(iNOS) and matrix metalloproteinases (MMPs) activity regulated by nuclear factor-kappa B transcription factor that play a key role in cancer as well as inflammation, demonstrating to be able to potentially apply to development of anti-inflammatory agent for chemoprevention of cancer. Furthermore, some macroalgae and their compounds with both excellent anti-inflammatory activity and very low toxicity can select a potential candidates capable of preventing or treating several chronic inflammation such as colitis, hepatitis and gastritis, leading to cancer.

Vaccinium oldhamii Stems Inhibit Pro-inflammatory Response and Osteoclastogenesis through Inhibition of NF-κB and MAPK/ATF2 Signaling Activation in LPS-stimulated RAW264.7 Cells

  • Park, Su Bin;Kim, Ha Na;Kim, Jeong Dong;Jeong, Jin Boo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2019.10a
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    • pp.67-67
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    • 2019
  • Vaccinium oldhamii (V. oldhamii) has been reported to exert a variety of the pharmacological properties such as anti-oxidant activity, anti-cancer activity, and inhibitory activity of ${\alpha}$-amylase and acetylcholinesterase. However, the anti-inflammatory activity of V. oldhamii has not been studied. In this study, we aimed to investigate anti-inflammatory activity of the stem extracts from V. oldhamii, and to elucidate the potential mechanisms in LPS-stimulated RAW264.7 cells. Among VOS, VOL and VOF, the inhibitory effect of NO and PGE2 production induced by LPS was highest in VOS treatment. Thus, VOS was selected for the further study. VOS dose-dependently blocked LPS-induced NO and PGE2 production by inhibiting iNOS and COX-2 expression, respectively. VOS inhibited the expression of pro-inflammatory cytokines such as $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$. In addition, VOS suppressed TRAP activity and attenuated the expression of the osteoclast-specific genes such as NFATc1, c-FOS, TRAP, MMP-9, cathepsin K, CA2, OSCAR and ATPv06d2. VOS inhibited LPS-induced $NF-{\kappa}B$ signaling activation through blocking $I{\kappa}B-{\alpha}$ degradation and p65 nuclear accumulation. VOS inhibited MAPK signaling activation by attenuating the phosphorylation of ERK1/2, p38 and JNK. Furthermore, VOS inhibited ATF2 phosphorylation and blocked ATF2 nuclear accumulation. From these findings, VOS has potential to be a candidate for the development of chemopreventive or therapeutic agents for the inflammatory diseases.

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Anti-inflammatory effects of HC001 on atopic dermatitis-like skin lesions in mice (HC001의 아토피성 피부염에 대한 항염증 효능 및 기전 연구)

  • Choi, You-Youn;Kim, Mi-Hye;Kum, Chang-Jun;Choi, Young-Jin;Hwang, Man-Ki;Sohn, Young-Joo;Jung, Hyuk-Sang;Yang, Woong-Mo
    • Herbal Formula Science
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    • v.20 no.1
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    • pp.41-49
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    • 2012
  • Objectives : The purpose of this study is to examine the effects of external application of HC001 on atopic dermatitis. HC001, newly composed herbal medicine combinations contains 9 medicinal herbs which are known to have anti-inflammatory and anti-allergic effects. We investigated the anti-inflammatory effects of HC001 on atopic dermatitis-like skin lesions in mice. Methods : Seven-week-old BALB/c mice were sensitized with DNCB to develop atopic dermatitis. Animals were divide into three group: Normal, DNCB (Negative control group), HC001 (Experimental group, treated with DNCB and HC001). Skin sections were stained with H&E to measure the thicknesses of the epidermis and dermis, respectively. The expression of NF-${\kappa}B$ protein was measured by western blotting analysis in skin lesion. Results : Topical HC001 treatment significantly restored the skin thickening and hyperplasia of the epidermis and dermis compared with DNCB-sensitized group in histopathological analyse. In addition, HC001 inhibited the expression of NF-${\kappa}B$ protein increased in DNCB-induced atopic dermatitis-like skin lesions in mice. Conclusions : These results suggest that HC001 may be useful as an external application agent for atopic dermatitis based on reductions of various inflammatory responses.

Neuronatin Is Associated with an Anti-Inflammatory Role in the White Adipose Tissue

  • Ka, Hye In;Han, Sora;Jeong, Ae Lee;Lee, Sunyi;Yong, Hyo Jeong;Boldbaatar, Ariundavaa;Joo, Hyun Jeong;Soh, Su Jung;Park, Ji Young;Lim, Jong-Seok;Lee, Myung Sok;Yang, Young
    • Journal of Microbiology and Biotechnology
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    • v.27 no.6
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    • pp.1180-1188
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    • 2017
  • Neuronatin (NNAT) is known to regulate ion channels during brain development and plays a role in maintaining the structure of the nervous system. A previous in silico analysis showed that Nnat was overexpressed in the adipose tissue of an obese rodent model relative to the wild type. Therefore, the aim of the present study was to investigate the function of Nnat in the adipose tissue. Because obesity is known to systemically induce low-grade inflammation, the Nnat expression level was examined in the adipose tissue obtained from C57BL/6 mice administered lipopolysaccharide (LPS). Unexpectedly, the Nnat expression level decreased in the white adipose tissue after LPS administration. To determine the role of NNAT in inflammation, 3T3-L1 cells overexpressing Nnat were treated with LPS. The level of the p65 subunit of nuclear factor-kappa B ($NF-{\kappa}B$) and the activity of $NF-{\kappa}B$ luciferase decreased following LPS treatment. These results indicate that NNAT plays an anti-inflammatory role in the adipose tissue.

Anti-Inflammatory Effect of Ethanol Extract from Grateloupia crispata on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Cells and Mice Ears (LPS로 유도된 RAW 264.7 세포와 마우스 귀 조직에 대한 주름까막살 에탄올 추출물의 항염증 효과)

  • Bae, Nan-Young;Kim, Min-Ji;Kim, Koth-Bong Woo-Ri;Park, Sun-Hee;Jang, Mi-Ran;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.8
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    • pp.1090-1098
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    • 2016
  • The anti-inflammatory effects of ethanol extract from Grateloupia crispata (GCEE) were investigated in lipopolysaccharide (LPS)-stimulated murine macrophages. Anti-inflammatory effects were detected by enzyme-linked immunosorbent assay, Western blotting, and immunohistochemistry. There was no cytotoxic effect on proliferation of macrophages treated with GCEE compared to the control. GCEE significantly inhibited production of pro-inflammatory cytokines [interleukin (IL)-6, tumor necrosis $factor-{\alpha}$, and $IL-1{\beta}$] as well as nitric oxide in LPS-stimulated RAW 264.7 cells. In addition, GCEE suppressed expression of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear $factor-{\kappa}B$ in a dose-dependent manner. GCEE significantly reduced activation of mitogen-activated protein kinases. In the in vivo test, evaluation of anti-inflammatory activity of GCEE was performed using croton oil-induced ear edema in ICR mice. Oral administration of 10 mg/kg to 250 mg/kg of GCEE significantly reduced ear edema in a dose-dependent manner compared to croton oil-induced mice. Moreover, GCEE reduced ear thickness and the number of mast cells compared to croton oil-induced mice in the histological analysis. These data suggest that GCEE could be used as a potential source for anti-inflammatory agents.

Quercetin Inhibits Inflammation Responses via MAPKs and NF-κB Signaling Pathways in LPS-stimulated RAW264.7 Cells (마우스 대식세포 RAW264.7 세포에서 MAPK와 NF-κB 경로를 통한 quercetin의 염증 반응 저해 활성)

  • Woo Young, Won;Jeong Tae, Kim;Keun Ho, Kim;Ji Young, Hwang;Chung-Wook, Chung;Jong Sik, Kim
    • Journal of Life Science
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    • v.32 no.11
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    • pp.899-907
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    • 2022
  • Quercetin is one of bio-flavonoids which are abundant in fruits and vegetables and has been reported to have various pharmacological potentials such as anti-oxidation, anti-inflammation, anti-cancer, and anti-virus effects. In the present study, the anti-inflammatory effects and its working molecular mecha- nism of quercetin were investigated in mouse macrophage RAW264.7 cells. Quercetin significantly inhibited nitric oxide (NO) production in a dose-dependent manner without affecting cell viability and decreased inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in LPS-stimulated RAW264.7 cells. In addition, quercetin decreased phosphorylation of p38, JNK, and ERK, and inhibited phosphorylation of NF-κB p65 protein and its inhibitor IκBα indicating that quercetin has the anti-inflammatory effects via regulation of MAPKs and NF-κB signaling pathway. We also detected expression changes of four kinds of pro-inflammatory cytokine genes (CSF2, IL-1β, IL-6, and TNF-α) with quantitative real-time PCR. The results showed that quercetin decreased the expression of four pro-inflammatory genes in LPS-stimulated RAW264.7 cells. Overall, our results showed that quercetin effectively suppressed inflammation responses induced by LPS in RAW264.7 cells via regulating MAPK and NF-κB pathway and down-regulating the expression of pro-inflammatory cytokine genes.

NF-${\kappa}$ B Activation and Cyclooxygenase-2 Expression Induced by Toll-Like Receptor Agonists can be Suppressed by Isoliquiritigenin (Isoliquiritigenin의 toll-like receptor agonists에 의해서 유도된 NF-${\kappa}$B 활성화와 cyclooxygenase-2 발현 억제)

  • Park, Se-Jeong;Yang, Seung-Ju;Youn, Hyung-Sun
    • Korean Journal of Food Science and Technology
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    • v.41 no.2
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    • pp.220-224
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    • 2009
  • Toll-like receptors(TLRs) are pattern recognition receptors(PRRs) that recognize pathogen-associated molecular patterns(PAMPs) and regulate the activation of innate immunity. All TLR signaling pathways culminate in the activation of NF-${\kappa}$B, leading to the induction of inflammatory gene products such as COX-2. Licorice (Glycyrrhiza uralensis) has been used for centuries as an herbal medicine. Isoliquiritigenin(ILG), a simple chalcone-type flavonoid, is an active component present in licorice and has been used to treat many chronic diseases. However, the mechanism as to how ILG mediates health effects is still largely unknown. In the present report, we present biochemical evidence that ILG inhibits the NF-${\kappa}$B activation induced by TLR agonists and the overexpression of downstream signaling components of TLRs, MyD88, IKK${\beta}$, and p65. ILG also inhibits TLR agonists-induced COX-2 expression. These results suggest that anti-inflammatory effects of ILG are caused by modulation of the immune responses regulated by TLR signaling pathways.