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.

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 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.

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 Suppression of Proinflammatory Cytokines and Mediators in LPS-Induced RAW 264.7 Macrophages by Stem Extract of Alternanthera sessilis via the Inhibition of the NF-κB Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Katyakyini Muniandy ◽  
Sivapragasam Gothai ◽  
Khaleel M. H. Badran ◽  
S. Suresh Kumar ◽  
Norhaizan Mohd Esa ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Proinflammatory Cytokines ◽  
Nuclear Translocation ◽  
Raw 264.7 ◽  
Alternanthera Sessilis ◽  
B Subunit ◽  
Proinflammatory Mediators ◽  
Short Period ◽  
Stem Extract ◽  
Cox 2

Alternanthera sessilis, an edible succulent herb, has been widely used as herbal drug in many regions around the globe. Inflammation is a natural process of the innate immune system, accompanied with the increase in the level of proinflammatory mediators, for example, nitric oxide (NO) and prostaglandin (PGE2); cytokines such as interleukin 6 (IL-6), interleukin 1β (IL-1β), and tumor necrosis factor alpha (TNFα); and enzymes including inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) via the activation and nuclear translocation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) subunit p65 due to the phosphorylation of inhibitory protein, IκBα. Inflammation over a short period of time is essential for its therapeutic effect. However, prolonged inflammation can be detrimental as it is related to many chronic diseases such as delayed wound healing, cardiovascular disease, arthritis, and autoimmune disorders. Therefore, ways to curb chronic inflammation have been extensively investigated. In line with that, in this present study, we attempted to study the suppression activity of the proinflammatory cytokines and mediators as a characteristic of anti-inflammatory action, by using stem extract of A. sessilis in the lipopolysaccharide- (LPS-) stimulated RAW 264.7 macrophage cell line. The results showed that the extract has significantly inhibited the production of the proinflammatory mediators including NO and PGE2; cytokines comprising IL-6, IL-1β, and TNFα; and enzymes covering the iNOS and COX-2 by preventing the IκBα from being degraded, to inhibit the nuclear translocation of NF-κB subunit p65 in order to hinder the inflammatory pathway activation. These results indicated that the stem extract of A. sessilis could be an effective candidate for ameliorating inflammatory-associated complications.

scholarly journals Anti-Inflammatory Effects of Bangpungtongsung-San, a Traditional Herbal Prescription

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Chul Won Lee ◽  
Sang Chan Kim ◽  
Tae Won Kwak ◽  
Jong Rok Lee ◽  
Mi Jeong Jo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Scientific Evidence ◽  
Raw 264.7 Cells ◽  
Prostaglandin E ◽  
Paw Edema ◽  
Proinflammatory Mediators ◽  
Mitogen Activated Protein ◽  
General Improvement ◽  
Anti Inflammatory ◽  
Herbal Prescription

Bangpungtongsung-san (BPTS), a traditional oriental herbal prescription, is widely used for expelling wind, draining heat, and providing general improvement to the immune system. In this study, we investigated the effects of BPTS on induction of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), proinflammatory cytokines, nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide- (LPS- ) stimulated Raw 264.7 cells, and on paw edema in rats. At concentrations of 0.5, 0.75, and 1 mg/mL, treatment with BPTS inhibited levels of expression of LPS-induced NF-κB and MAPKs (ERK, JNK, and p38) as well as production of proinflammatory mediators, such as nitric oxide (NO), prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6) by LPS. These results suggest that BPTS may exert anti-inflammatory effects via reduction of proinflammatory mediators, including NO, PGE2, TNF-α, and IL-6 through suppression of the signaling pathways of NF-κB and MAPKs in LPS-induced macrophages. In addition, using the carrageenan-induced paw edema assay, an antiedema effect of BPTS was observed in rats. These findings may provide scientific evidence validating the use of BPTS in treatment of patients with heat syndrome in Korean oriental medicine.

scholarly journals Antibacterial and Anti-Inflammatory Activities ofPhysalis Alkekengivar.franchetiiand Its Main Constituents

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Zunpeng Shu ◽  
Na Xing ◽  
Qiuhong Wang ◽  
Xinli Li ◽  
Bingqing Xu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Interleukin 1 ◽  
Inflammatory Activity ◽  
Prostaglandin E ◽  
Active Components ◽  
Necrosis Factor Alpha ◽  
Anti Inflammatory

This study was designed to determine whether the 50% EtOH fraction from AB-8 macroporous resin fractionation of a 70% EtOH extract ofP. Alkekengi(50-EFP) has antibacterial and/or anti-inflammatory activity bothin vivoandin vitroand to investigate the mechanism of 50-EFP anti-inflammatory activity. Additionally, this study sought to define the chemical composition of 50-EFP. Results indicated that 50-EFP showed significant antibacterial activityin vitroand efficacyin vivo. Moreover, 50-EFP significantly reduced nitric oxide (NO), prostaglandin E2(PGE2), tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1), and interleukin 6 (IL-6) production in lipopolysaccharide- (LPS-) stimulated THP-1 cells. Nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) (examined at the protein level) in THP-1 cells were suppressed by 50-EFP, which inhibited nuclear translocation of p65. Consistent with this anti-inflammatory activityin vitro, 50-EFP reduced inflammation in both animal models. Finally, seventeen compounds (8 physalins and 9 flavones) were isolated as major components of 50-EFP. Our data demonstrate that 50-EFP has antibacterial and anti-inflammatory activities bothin vitroandin vivo. The anti-inflammatory effect appears to occur, at least in part, through the inhibition of nuclear translocation of p65. Moreover, physalins and flavones are probably the active components in 50-EFP that exert antibacterial and anti-inflammatory activities.

scholarly journals Regulation of Proinflammatory Mediators via NF-κB and p38 MAPK-Dependent Mechanisms in RAW 264.7 Macrophages by Polyphenol Components Isolated from KoreaLonicera japonica THUNB

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Kwang-Il Park ◽  
Sang-Rim Kang ◽  
Hyeon-Soo Park ◽  
Do Hoon Lee ◽  
Arulkumar Nagappan ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Nuclear Translocation ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Necrosis Factor Alpha ◽  
Proinflammatory Mediators ◽  
Mapk Activity ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory

Lonicera japonica THUNB., which abundantly contains polyphenols, has been used as a traditional medicine for thousands of years in East Asian countries because of the anti-inflammation properties. This study aimed to investigate the anti-inflammatory mechanism of polyphenol components isolated from KoreaL. japonica T.by nuclear factor-kappaB (NF-κB) and mitogen-activated protein kinases (MAPKs) pathway. Polyphenols significantly decreased lipopolysaccharide- (LPS-) induced mRNA and protein expression of inducible nitric oxide synthase and cyclooxygenase-2, as well as mRNA expression of tumor necrosis factor-alpha, interleukin- (IL-) 1β, and IL-6. Moreover, polyphenols inhibited nuclear translocation of NF-κB p65, phosphorylation/degradation of the inhibitor ofκB, and phosphorylation of p38 MAPK, whereas the extracellular signal-regulated kinase and Janus N-terminal kinase were not affected. These results indicate that polyphenol components isolated from KoreaL. japonica T.should have anti-inflammatory effect on LPS-stimulated RAW 264.7 cells through the decrease of proinflammatory mediators expression by suppressing NF-κB and p38 MAPK activity.

(+)-Catechin Attenuates NF-κB Activation Through Regulation of Akt, MAPK, and AMPK Signaling Pathways in LPS-Induced BV-2 Microglial Cells

2015 ◽  
Vol 43 (05) ◽  
pp. 927-952 ◽  
Author(s):  
Sharifah Salwa Syed Hussein ◽  
Muhamad Noor Alfarizal Kamarudin ◽  
Habsah Abdul Kadir
Keyword(s):  
P38 Mapk ◽  
Nuclear Translocation ◽  
Adenosine Monophosphate ◽  
Nuclear Factor Κb ◽  
Microglial Cells ◽  
Mechanistic Study ◽  
Ampk Signaling ◽  
Proinflammatory Mediators ◽  
Mitogen Activated Protein ◽  
Cox 2

(+)-catechin is a flavanol that possesses various health and medicinal values, which include neuroprotection, anti-oxidation, antitumor and antihepatitis activities. This study investigated the modulatory effects of (+)-catechin on the lipopolysaccharides (LPS)-stimulated BV-2 cells. (+)-catechin attenuated LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and inhibited microglial NO and ROS production. Additionally, (+)-catechin suppressed the production of tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, while augmenting IL-4. (+)-catechin attenuated LPS-induced nuclear factor-κB (NF-κB) p65 nuclear translocation via the inhibition of IκB-α phosphorylation. Moreover, (+)-catechin blocked the activation of Akt and its inhibition was shown to play a crucial role in LPS-induced inflammation in BV-2 microglial cells. (+)-catechin also attenuated the LPS-induced phosphorylation of extracellular signal-regulated kinase (ERK1/2), and p-38 mitogen activated protein kinases (p38 MAPK) and specific inhibitors of ERK1/2 (UO126) and p38 MAPK (SB202190) subsequently down-regulated the expression of the proinflammatory mediators iNOS and COX-2. Further mechanistic study revealed that (+)-catechin acted through the amelioration of the LPS-induced suppression of adenosine monophosphate-activated protein kinase (AMPK) activity. Taken together, our data indicate that (+)-catechin exhibits anti-inflammatory effects in BV-2 cells by suppressing the production of proinflammatory mediators and mitigation of NF-κB through Akt, ERK, p38 MAPK, and AMPK pathways.

scholarly journals Sec22b regulates inflammatory responses by controlling the nuclear translocation of NF-κB

2020 ◽  
Author(s):  
Guillermo Arango Duque ◽  
Renaud Dion ◽  
Aymeric Fabié ◽  
Julien Descoteaux ◽  
Simona Stäger ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dendritic Cells ◽  
Secretory Pathway ◽  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Phagocytic Cells ◽  
Mitogen Activated Protein ◽  
And Function

AbstractSoluble NSF attachment receptor (SNARE) proteins regulate the vesicle transport machinery in phagocytic cells. Within the secretory pathway, Sec22b is an ER-Golgi intermediate compartment (ERGIC)-resident SNARE that controls phagosome maturation and function in macrophages and dendritic cells. The secretory pathway controls the release of cytokines and may also impact the secretion of nitric oxide (NO), which is synthesized by the Golgi-active inducible nitric oxide synthase (iNOS). Whether ERGIC SNARE Sec22b controls NO and cytokine secretion, is unknown. Using bone marrow-derived dendritic cells (BMDC), we demonstrated that iNOS colocalizes with ERGIC/Golgi markers, notably Sec22b and its partner syntaxin-5 (Stx5), in the cytoplasm and at the phagosome. Pharmacological blockade of the secretory pathway hindered NO and cytokine release, and inhibited NF-κB translocation to the nucleus. Importantly, RNAi-mediated silencing of Sec22b revealed that NO and cytokine production were abrogated at the protein and mRNA levels. This correlated with deregulated mitogen-activated protein kinase signalling and reduced nuclear translocation of NF-κB. We also found that Sec22b co-occurs with NF-κB in both the cytoplasm and nucleus, pointing to a role for this SNARE in the shuttling of NF-κB. Collectively, our data unveiled a novel function for the ER-Golgi, and its resident SNARE Sec22b, in the production and release of inflammatory mediators.

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.

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