Eriobotryae Folium Extract Suppresses LPS-Induced iNOS and COX-2 Expression by Inhibition of NF-κB and MAPK Activation in Murine Macrophages

2010 ◽  
Vol 38 (05) ◽  
pp. 985-994 ◽  
Author(s):  
Takuhiro Uto ◽  
Natnaprach Suangkaew ◽  
Osamu Morinaga ◽  
Hiroko Kariyazono ◽  
Shigeru Oiso ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Skin Diseases ◽  
Binding Activity ◽  
Eriobotrya Japonica ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Cox 2

Eriobotryae folium (EF), the dried leaves of Eriobotrya japonica (Thunb.) Lindl. has been traditionally used to treat various diseases such as chronic bronchitis, cough, inflammation, skin diseases, and diabetes. In this study, we examined the effects of Eriobotryae folium extract (EFE) on lipopolysaccharide (LPS)-induced production of nitric oxide (NO) and prostaglandin E2(PGE2) in RAW264 murine macrophage cells. EFE suppressed LPS-induced NO and PGE2 production in a dose-dependent manner. Consistent with these observations, EFE reduced the LPS-induced expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) at both protein and mRNA levels. Furthermore, EFE significantly inhibited LPS-induced NF-κB binding activity, which was associated with the inhibition of IκB-α degradation. EFE also attenuated LPS-induced phosphorylation of mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated kinase (ERK), p38 MAPK and c-Jun N-terminal kinase (JNK). These results suggest that the anti-inflammatory properties of EF might result from inhibition of iNOS and COX-2 expression through the downregulation of NF-κB activation and MAPK phosphorylation in LPS-stimulated RAW264 cells.

scholarly journals Oleifolioside A, a New Active Compound, Attenuates LPS-Stimulated iNOS and COX-2 Expression through the Downregulation of NF-κB and MAPK Activities in RAW 264.7 Macrophages

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Hai Yang Yu ◽  
Kyoung-Sook Kim ◽  
Young-Choon Lee ◽  
Hyung-In Moon ◽  
Jai-Heon Lee
Keyword(s):  
Nitric Oxide ◽  
Mapk Signaling ◽  
Binding Activity ◽  
Prostaglandin E ◽  
Raw 264.7 ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Raw 264.7 Macrophages ◽  
Dendropanax Morbifera ◽  
Cox 2

Oleifolioside A, a new triterpenoid compound isolated fromDendropanax morbiferaLeveille (D. morbifera), was shown in this study to have potent inhibitory effects on lipopolysaccharide (LPS-)stimulated nitric oxide (NO) and prostaglandin E2(PGE2) production in RAW 264.7 macrophages. Consistent with these findings, oleifolioside A was further shown to suppress the expression of LPS-stimulated inducible nitric oxide synthase (iNOS) and cyclooxigenase-2 (COX-2) in a dose-dependent manner at both the protein and mRNA levels and to significantly inhibit the DNA-binding activity and transcriptional activity of NF-κB in response to LPS. These results were found to be associated with the inhibition of the degradation and phosphorylation of IκB-αand subsequent translocation of the NF-κB p65 subunit to the nucleus. Inhibition of NF-κB activation by oleifolioside A was also shown to be mediated through the prevention of p38 MAPK and ERK1/2 phosphorylation. Taken together, our results suggest that oleifolioside A has the potential to be a novel anti-inflammatory agent capable of targeting both the NF-κB and MAPK signaling pathways.

scholarly journals Inhibition of Neuroinflammation in LPS-Activated Microglia by Cryptolepine

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Olumayokun A. Olajide ◽  
Harsharan S. Bhatia ◽  
Antonio C. P. de Oliveira ◽  
Colin W. Wright ◽  
Bernd L. Fiebich
Keyword(s):  
Nitric Oxide ◽  
Microglial Activation ◽  
Nuclear Translocation ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Necrosis Factor Alpha ◽  
Microglia Cell ◽  
Proinflammatory Mediators ◽  
Mitogen Activated Protein ◽  
Cox 2

Cryptolepine, an indoloquinoline alkaloid inCryptolepis sanguinolenta, has anti-inflammatory property. In this study, we aimed to evaluate the effects of cryptolepine on lipopolysaccharide (LPS)- induced neuroinflammation in rat microglia and its potential mechanisms. Microglial activation was induced by stimulation with LPS, and the effects of cryptolepine pretreatment on microglial activation and production of proinflammatory mediators, PGE2/COX-2, microsomal prostaglandin E2synthase and nitric oxide/iNOS were investigated. We further elucidated the role of Nuclear Factor-kappa B (NF-κB) and the mitogen-activated protein kinases in the antiinflammatory actions of cryptolepine in LPS-stimulated microglia. Our results showed that cryptolepine significantly inhibited LPS-induced production of tumour necrosis factor-alpha (TNFα), interleukin-6 (IL-6), interleukin-1beta (IL-1β), nitric oxide, and PGE2. Protein and mRNA levels of COX-2 and iNOS were also attenuated by cryptolepine. Further experiments on intracellular signalling mechanisms show that IκB-independent inhibition of NF-κB nuclear translocation contributes to the anti-neuroinflammatory actions of cryptolepine. Results also show that cryptolepine inhibited LPS-induced p38 and MAPKAPK2 phosphorylation in the microglia. Cell viability experiments revealed that cryptolepine (2.5 and 5 μM) did not produce cytotoxicity in microglia. Taken together, our results suggest that cryptolepine inhibits LPS-induced microglial inflammation by partial targeting of NF-κB signalling and attenuation of p38/MAPKAPK2.

scholarly journals β-Patchoulene, isolated from patchouli oil, suppresses inflammatory mediators in LPS-stimulated RAW264.7 macrophages

2017 ◽  
Vol 15 (2) ◽  
pp. 136-141 ◽  
Author(s):  
Wen-Hao Yang ◽  
Yu-Hong Liu ◽  
Jia-Li Liang ◽  
Zhi-Xiu Lin ◽  
Qiu-Lin Kong ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Messenger Rna ◽  
Inflammatory Activity ◽  
Prostaglandin E ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Raw264.7 Macrophages ◽  
Cox 2 ◽  
Anti Inflammatory

β-Patchoulene (β-PAE) is a tricyclic sesquiterpene isolated from patchouli oil. According to our previous study, β-PAE has anti-inflammatory activity in vivo; however, its anti-inflammatory response still remains unconfirmed in vitro. Therefore, this study is committed to demonstrate the anti-inflammatory effect of β-PAE on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. According to our results, pre-treatment with β-PAE significantly decreased the protein and messenger RNA (mRNA) levels of pro-inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β while increased the expressions of anti-inflammatory cytokines like IL-10 in a dose-dependent manner. In addition, real-time polymerase chain reaction (PCR) also revealed that β-PAE could interrupt the mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and thus decreased the levels of nitric oxide (NO) and prostaglandin E2 (PGE2) in LPS-stimulated RAW264.7 macrophages. In conclusion, these results indicated that β-PAE exerted potent anti-inflammatory activity by maintaining the balance between pro- and anti-inflammatory cytokines as well as suppressing iNOS and COX-2 signaling pathways.

p38 MAPK and NF-κB mediate COX-2 expression in human airway myocytes

2003 ◽  
Vol 285 (5) ◽  
pp. L1087-L1098 ◽  
Author(s):  
Cherie A. Singer ◽  
Kimberly J. Baker ◽  
Alan McCaffrey ◽  
David P. AuCoin ◽  
Melissa A. Dechert ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Binding Activity ◽  
Dependent Manner ◽  
Human Airway ◽  
Mitogen Activated Protein ◽  
Steady State Levels ◽  
Cox 2 ◽  
P38 Mapk Inhibitor ◽  
Factor Α ◽  
Sb 203580

We have previously demonstrated that p38 and extracellular signal-regulated protein kinase (ERK) mitogen-activated protein kinases (MAPK) are components of proinflammatory induced cytokine expression in human airway myocytes. The experiments described here further these studies by examining p38 MAPK and NF-κB regulation of cyclooxygenase-2 (COX-2) expression in response to a complex inflammatory stimulus consisting of 10 ng/ml interleukin (IL)-1β, tumor necrosis factor-α (TNF-α), and interferon (IFN)-γ. COX-2 expression was induced with this stimulus in a time-dependent manner, with maximal expression seen 12-20 h after treatment. Semiquantitative RT-PCR and immunoblotting experiments demonstrate decreased COX-2 expression following treatment with the p38 MAPK inhibitor SB-203580 (25 μM) or the proteosome inhibitor MG-132 (1 μM). SB-203580 did not affect cytokine-stimulated IκBα degradation, NF-κB nuclear binding activity, or NF-κB-dependent signaling from the COX-2 promoter, indicating that p38 MAPK and NF-κB may affect COX-2 expression via separate signaling pathways. SB-203580, but not MG-132, also increased the initial rate of COX-2 mRNA decay, indicating p38 MAPK, but not NF-κB, participates in the regulation of COX-2 mRNA stability. These findings suggest that although p38 MAPK and NF-κB signaling regulate steady-state levels of COX-2 expression, p38 MAPK additionally affects stability of COX-2 mRNA in cytokine-stimulated human airway myocytes.

Signaling Pathways Regulating IL-1α-induced COX-2 Expression

2007 ◽  
Vol 86 (2) ◽  
pp. 186-191 ◽  
Author(s):  
S. Ogata ◽  
Y. Kubota ◽  
T. Yamashiro ◽  
H. Takeuchi ◽  
T. Ninomiya ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mrna Expression ◽  
Signaling Pathways ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Odontogenic Keratocyst ◽  
Prostaglandin E ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Cox 2

Interleukin-1α(IL-1α) stimulates the production of prostaglandin E2 (PGE2) in odontogenic keratocyst fibroblasts. However, the signaling pathways remain obscure. In this study, we investigated IL-1αsignaling pathways that regulate cyclooxygenase-2 (COX-2) expression in odontogenic keratocyst fibroblasts. IL-1αincreased the expression of COX-2 mRNA and protein, and PGE2 secretion in the fibroblasts. IL-1αincreased the phosphorylation of extracellular signal-regulated protein kinase-1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK). PD-98059, SB-203580, SP-600125, and PDTC—which are inhibitors of ERK1/2, p38, JNK, and nuclear factor-κB (NF-κB), respectively—attenuated the IL-1α-induced COX-2 mRNA expression and activated protein kinase C PGE2 secretion. IL-1α(PKC), and PKC inhibitor staurosporine inhibited IL-1α-induced phosphorylation of ERK1/2, p38, and JNK, and decreased IL-1α-induced COX-2 mRNA expression. Thus, in odontogenic keratocyst fibroblasts, IL-1αmay stimulate COX-2 expression both through the PKC-dependent activation of ERK1/2, p38, and JNK signaling pathways, and through the NF-κB cascade.

scholarly journals Anti-Inflammatory Effects ofArtemisiaLeaf Extract in Mice with Contact DermatitisIn VitroandIn Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Chanyong Yun ◽  
Youngchul Jung ◽  
Wonjoo Chun ◽  
Beodeul Yang ◽  
Junghyun Ryu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cytokine Production ◽  
Skin Diseases ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Raw 264.7 ◽  
Inflammatory Skin Diseases ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Oxide Synthase

The leaves ofArtemisia argyiLev. et Vant. andA. princepsPamp. are well known medicinal herbs used to treat patients in China, Japan, and Korea with skin problems such as eczema and itching, as well as abdominal pain and dysmenorrhoea. We investigated the anti-inflammatory effects ofArtemisialeaf extract (ALE) using CD mice and Raw 264.7 cells. The effects of ALE on histopathological changes and cytokine production in ear tissues were assessed in mice with CD induced by 1-fluoro-2,4-dinitrobenzene (DNFB). Moreover, the anti-inflammatory effects on production levels of prostaglandin E2(PGE2) and nitric oxide (NO) and expression levels of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) were investigated in Raw 264.7 cells. Topical application of ALE effectively prevented ear swelling induced by repeated DNFB application. ALE prevented epidermal hyperplasia and infiltration of immune cells and lowered the production of interferon- (IFN-) gamma (γ), tumour necrosis factor- (TNF-) alpha (α), and interleukin- (IL-) 6 in inflamed tissues. In addition, ALE inhibited expression of COX-2 and iNOS and production of NO and PGE2in Raw 264.7 cells. These results indicate thatArtemisialeaf can be used as a therapeutic agent for inflammatory skin diseases and that its anti-inflammatory effects are closely related to the inhibition of inflammatory mediator release from macrophages and inflammatory cytokine production in inflamed tissues.

scholarly journals Anti-Inflammatory Effects and Mechanisms ofFatsia polycarpaHayata and Its Constituents

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Hsueh-Ling Cheng ◽  
Nurkholis ◽  
Shi-Yie Cheng ◽  
Shen-Da Huang ◽  
Yan-Ting Lu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Interleukin 1 ◽  
Prostaglandin E ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Fatsia polycarpa, a plant endemic to Taiwan, is an herbal medicine known for treating several inflammation-related diseases, but its biological function needs scientific support. Thus, the anti-inflammatory effects and mechanisms of the methanolic crude extract (MCE) ofF. polycarpaand its feature constituents, that is, brassicasterol (a phytosterol), triterpenoids 3α-hydroxyolean-11,13(18)-dien-28-oic acid (HODA), 3α-hydroxyolean-11-en-28,13β-olide (HOEO), fatsicarpain D, and fatsicarpain F, were investigated. MCE and HOEO, but not brassicasterol, dose-dependently inhibited lipopolysaccharide- (LPS-)induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophage line, whereas HODA, fatsicarpain D and fatsicarpain F were toxic to RAW cells. Additionally, MCE and HOEO suppressed LPS-induced production of nitric oxide, prostaglandin E2, and interleukin-1βand interfered with LPS-promoted activation of the inhibitor kappa B kinase (IKK)/nuclear factor-κB (NF-κB) pathway, and that of the mitogen-activated protein kinases (MAPKs) extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In animal tests, MCE and HOEO effectively ameliorated 12-O-tetradecanoylphorobol-13 acetate- (TPA-)induced ear edema of mice. Thus, MCE ofF. polycarpaexhibited an obvious anti-inflammatory activityin vivoandin vitrothat likely involved the inhibition of the IKK/NF-κB pathway and the MAPKs, which may be attributed by triterpenoids such as HOEO.

scholarly journals Bojesodok-eum, a Herbal Prescription, Ameliorates Acute Inflammation in Association with the Inhibition of NF-κB-Mediated Nitric Oxide and ProInflammatory Cytokine Production

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Kook Ho Sohn ◽  
Mi Jeong Jo ◽  
Won Joon Cho ◽  
Jong Rok Lee ◽  
Il Je Cho ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Proinflammatory Cytokines ◽  
Cell Model ◽  
Raw264.7 Cells ◽  
Prostaglandin E ◽  
Dependent Manner ◽  
Paw Edema ◽  
Edema Formation ◽  
Cox 2 ◽  
Herbal Prescription

Bojesodok-eum(BSE) is a herbal prescription consisting ofCoptidis RhizomaandScutellariae Radixas main components. This paper investigated the effects of BSE on the induction of nitric oxide (NO), prostaglandin E2(PGE2), and proinflammatory cytokines that are caused by lipopolysaccharide (LPS) in murine macrophage cell line and on the paw edema formation in animals. Administration of BSE (0.3 g/kg and 1 g/kg) in rats significantly inhibited carrageenan-induced paw edema formation, as did dexamethasone, an anti-inflammatory positive control drug. In cell model, treatment of BSE decreased the production of NO and PGE2in RAW264.7 cells stimulated by LPS. BSE also inhibited the expression of iNOS and COX-2 protein as well as COX activity in a concentration-dependent manner. Consistently, BSE suppressed the ability of LPS to produce TNF-α, interleukin-1β, and interleukin-6. LPS treatment induced nuclear NF-κB level and I-κBαphosphorylation, which were inhibited subsequent treatment of BSE, suggesting its repression of LPS-inducible NF-κB activation. BSE abrogated the induction of NO, PGE2, and proinflammatory cytokines, as well as iNOS and COX-2 protein expression in RAW264.7 cells stimulated by LPS as mediated with NF-κB inhibition.

scholarly journals Preventive Effects of a Kampo Medicine, Kakkonto, on Inflammatory Responses via the Suppression of Extracellular Signal-Regulated Kinase Phosphorylation in Lipopolysaccharide-Treated Human Gingival Fibroblasts

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Hiroyuki Kitamura ◽  
Hiroko Urano ◽  
Toshiaki Ara
Keyword(s):  
Periodontal Disease ◽  
Inflammatory Responses ◽  
Human Gingival Fibroblasts ◽  
Kampo Medicine ◽  
Prostaglandin E ◽  
Gingival Fibroblasts ◽  
Extracellular Signal Regulated Kinase ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Cox 2

Periodontal disease is accompanied by inflammation of the gingiva and destruction of periodontal tissues, leading to alveolar bone loss in severe clinical cases. The chemical mediator prostaglandin E2 (PGE2) and cytokines such as interleukin- (IL-)6 and IL-8 have been known to play important roles in inflammatory responses and tissue degradation. In the present study, we investigated the effects of a kampo medicine, kakkonto (TJ-1), on the production of prostaglandin E2 (PGE2), IL-6, and IL-8 by human gingival fibroblasts (HGFs) treated with lipopolysaccharide (LPS) from Porphyromonas gingivalis. Kakkonto concentration dependently suppressed LPS-induced PGE2 production but did not alter basal PGE2 levels. In contrast, kakkonto significantly increased LPS-induced IL-6 and IL-8 production. Kakkonto decreased cyclooxygenase- (COX-)1 activity to approximately 70% at 1 mg/mL but did not affect COX-2 activity. Kakkonto did not affect cytoplasmic phospholipase A2 (cPLA2), annexin1, or LPS-induced COX-2 expression. Kakkonto suppressed LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation, which is known to lead to ERK activation and cPLA2 phosphorylation. These results suggest that kakkonto decreased PGE2 production by inhibition of ERK phosphorylation which leads to inhibition of cPLA2 phosphorylation and its activation. Therefore, kakkonto may be useful to improve gingival inflammation in periodontal disease.

scholarly journals Sargassum fulvellumProtects HaCaT Cells and BALB/c Mice from UVB-Induced Proinflammatory Responses

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Chan Lee ◽  
Gyu Hwan Park ◽  
Eun Mi Ahn ◽  
Chan-Ik Park ◽  
Jung-Hee Jang
Keyword(s):  
Nitric Oxide ◽  
Ethanol Extract ◽  
Prostaglandin E ◽  
Hacat Cells ◽  
Uvb Irradiation ◽  
Proinflammatory Mediators ◽  
Sargassum Fulvellum ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Skin Damages

Ultraviolet (UV) radiation has been reported to induce cutaneous inflammation such as erythema and edema via induction of proinflammatory enzymes and mediators.Sargassum fulvellumis a brown alga of Sargassaceae family which has been demonstrated to exhibit antipyretic, analgesic, antiedema, antioxidant, antitumor, fibrinolytic, and hepatoprotective activities. The purpose of this study is to investigate anti-inflammatory effects of ethylacetate fraction of ethanol extract ofSargassum fulvellum(SFE-EtOAc) in HaCaT keratinocytes and BALB/c mice. In HaCaT cells, SFE-EtOAc effectively inhibited UVB-induced cytotoxicity (60 mJ/cm2) and the expression of proinflammatory proteins such as cyclooxygenase-2 (COX-2), tumor necrosis factor-α(TNF-α), and inducible nitric oxide synthase (iNOS). Furthermore, SFE-EtOAc significantly reduced UVB-induced production of proinflammatory mediators including prostaglandin E2(PGE2) and nitric oxide (NO). In BALB/c mice, topical application of SFE-EtOAc prior to UVB irradiation (200 mJ/cm2) effectively suppressed the UVB-induced protein expression of COX-2, iNOS, and TNF-αand subsequently attenuated generation of PGE2and NO as well. In another experiment, SFE-EtOAc pretreatment suppressed UVB-induced reactive oxygen species production and exhibited an antioxidant potential by upregulation of antioxidant enzymes such as catalase and Cu/Zn-superoxide dismutase in HaCaT cells. These results suggest that SFE-EtOAc could be an effective anti-inflammatory agent protecting against UVB irradiation-induced skin damages.

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