scholarly journals Bioactive Compounds in Moringa oleifera Lam. Leaves Inhibit the Pro-Inflammatory Mediators in Lipopolysaccharide-Induced Human Monocyte-Derived Macrophages

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 191 ◽  
Author(s):  
Thitiya Luetragoon ◽  
Rungnapa Pankla Sranujit ◽  
Chanai Noysang ◽  
Yordhathai Thongsri ◽  
Pachuen Potup ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Moringa Oleifera ◽  
Nuclear Translocation ◽  
Human Monocyte ◽  
Protein Levels ◽  
Tnf Α ◽  
Phytochemical Compounds ◽  
Extract Fraction ◽  
Flash Column Chromatography ◽  
Tuberonic Acid

Moringa oleifera (MO) is an important plant for traditional medicine. The present study aimed to identify the MO active phytochemical compounds for their ability against inflamed macrophages. An ethyl acetate extract fraction of MO was fractionation by flash column chromatography. Human macrophages were stimulated by Lipopolysaccharide and then treated with fractions of MO to examine their anti-inflammatory activity and cellular mechanism. The active fractions were analyzed by liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometer (LC-ESI-QTOF-MS). MO treated cells showed a decreased production of pro-inflammatory mediator in response to lipopolysaccharide. This was evident at both mRNA and protein levels. The study revealed that MO suppressed mRNA expression of IL-1, IL-6, TNF-α, PTGS2, NF-κB (P50), and RelA. Furthermore, the extract effectively inhibited the expression of inflammatory mediators, including IL-6, TNF-α, and cyclooxygenase-2. Interestingly, the effect of MO inhibited phosphorylation of IκB-α and the ability to reduce expression of the nuclear factor (NF)-κB p65, suppressing its nuclear translocation. Moreover, LC-ESI-QTOF-MS analysis of the MO active fraction revealed seven compounds, namely 3,4-Methyleneazelaic acid, (2S)-2-phenylmethoxybutane-1,4-diol, (2R)-2-phenylmethoxybutane-1, 4-diol, γ-Diosphenol, 2,2,4,4-Tetramethyl-6-(1-oxobutyl)-1,3,5-cyclohexanetrione, 3-Hydroxy-β-ionone, and Tuberonic acid. Our findings highlight the ability of MO compounds to inhibit inflammation through regulation of the NF-κB pathway.

Spiranthes sinensis Suppresses Production of Pro-Inflammatory Mediators by Down-Regulating the NF-κB Signaling Pathway and Up-Regulating HO-1/Nrf2 Anti-Oxidant Protein

2015 ◽  
Vol 43 (05) ◽  
pp. 969-989 ◽  
Author(s):  
Pei-Hsin Shie ◽  
Shyh-Shyun Huang ◽  
Jeng-Shyan Deng ◽  
Guan-Jhong Huang
Keyword(s):  
Inflammatory Mediators ◽  
Nuclear Translocation ◽  
Ethyl Acetate Fraction ◽  
Raw264.7 Cells ◽  
Prostaglandin E ◽  
Protein Levels ◽  
Tnf Α ◽  
Anti Oxidant ◽  
Spiranthes Sinensis

Spiranthes sinensis is an east Asian wild orchid used in Chinese folk medicine. In this study, an ethyl acetate fraction from S. sinensis(SSE) was found to suppress the production of LPS-stimulated inflammatory mediators in RAW264.7 cells and BALB/c mice. SSE inhibited the production of pro-inflammatory mediators such as nitric oxide (NO), prostaglandin E2 (PGE2), tumo necrosis factor-α (TNF-α), IL-1β, and IL-6 in LPS-stimulated RAW264.7 cells. SSE also significantly suppressed LPS-stimulated protein levels of iNOS and mPGES-1 by blocking IκB phosphorylation, NF-κB nuclear translocation, and MAPKs phosphorylation. In addition, SSE treatment also enhanced protein levels of HO-1 and anti-oxidant enzymes (SOD-1, CAT, and GPx-1) through the nuclear translocation of Nrf2 in LPS-stimulated RAW264.7 cells. In vivo, we demonstrated that SSE attenuated the levels of pro-inflammatory mediators (NO, TNF-α, IL-1β, and IL-6), ALT, and AST in the serum of LPS-stimulated BALB/c mice. Western blotting revealed that SSE enhanced HO-1 expression in lung and liver tissue after LPS injection in mice. These results suggest that the anti-inflammatory properties of SSE involve the suppression of iNOS, mPGES-1, and inflammatory mediators by inducing the HO-1 pathway in LPS-stimulated RAW264.7 cells and BALB/c mice.

Brief murine myocardial I/R induces chemokines in a TNF-α-independent manner: role of oxygen radicals

2001 ◽  
Vol 281 (6) ◽  
pp. H2549-H2558 ◽  
Author(s):  
Tareck O. Nossuli ◽  
Nikolaos G. Frangogiannis ◽  
Pascal Knuefermann ◽  
Venkatesh Lakshminarayanan ◽  
Oliver Dewald ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Nuclear Factor Κb ◽  
Radical Scavenger ◽  
Reactive Oxygen Intermediate ◽  
Area At Risk ◽  
Independent Manner ◽  
Protein Levels ◽  
Inflammatory Protein ◽  
Tnf Α ◽  
Venular Endothelium

Early chemokine induction in the area at risk of an ischemic-reperfused (I/R) myocardium is first seen in the venular endothelium. Reperfusion is associated with several induction mechanisms including increased extracellular tumor necrosis factor (TNF)-α, reactive oxygen intermediate (ROI) species formation, and adhesion of leukocytes to the venular endothelium. To test the hypothesis that chemokine induction in cardiac venules can occur by ROIs in a TNF-α-independent manner, and in the absence of leukocyte accumulation, we utilized wild-type (WT) and TNF-α double-receptor knockout mice (DKO) in a closed-chest mouse model of myocardial ischemia (15 min) and reperfusion (3 h), in which there is no infarction. We demonstrate that a single brief period of I/R induces significant upregulation of the chemokines macrophage inflammatory protein (MIP) -1α, -1β, and -2 at both the mRNA and protein levels. This induction was independent of TNF-α, whereas levels of these chemokines were increased in both WT and DKO mice. Chemokine induction was seen predominantly in the endothelium of small veins and was accompanied by nuclear translocation of nuclear factor-κB and c-Jun (AP-1) in venular endothelium. Intravenous infusion of the oxygen radical scavenger N-2-mercaptopropionyl glycine (MPG) initiated 15 min before ischemia and maintained throughout reperfusion obviated chemokine induction, but MPG administration after reperfusion had begun had no effect. The results suggest that ROI generation in the reperfused myocardium rapidly induces C-C and C-X-C chemokines in the venular endothelium in the absence of infarction or irreversible cellular injury.

Moringa Fruit Inhibits LPS-Induced NO/iNOS Expression through Suppressing the NF-κB Activation in RAW264.7 Cells

2013 ◽  
Vol 41 (05) ◽  
pp. 1109-1123 ◽  
Author(s):  
Hyo-Jin Lee ◽  
Yun-Jeong Jeong ◽  
Tae-Sung Lee ◽  
Yoon-Yub Park ◽  
Whi-Gun Chae ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Mediators ◽  
Nuclear Translocation ◽  
Biologically Active ◽  
Raw264.7 Cells ◽  
No Production ◽  
Dependent Manner ◽  
Fruit Extract ◽  
Tnf Α ◽  
Anti Inflammatory

In this study, we evaluated the anti-inflammatory effects of moringa (Moringa oleifera Lam.), a natural biologically active substance, by determining its inhibitory effects on pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophage RAW264.7 cells. Extracts from different parts of moringa (root, leaf, and fruit) reduced LPS-induced nitric oxide (NO) release in a dose-dependent manner. The moringa fruit extract most effectively inhibited LPS-induced NO production and levels of inducible nitric oxide synthase (iNOS). The moringa fruit extract also was shown to suppress the production of inflammatory cytokines including IL-1β, TNF-α, and IL-6. Furthermore, moringa fruit extract inhibited the cytoplasmic degradation of I κ B -α and the nuclear translocation of p65 proteins, resulting in lower levels of NF -κ B transactivation. Collectively, the results of this study demonstrate that moringa fruit extract reduces the levels of pro-inflammatory mediators including NO , IL-1β, TNF-α, and IL-6 via the inhibition of NF -κ B activation in RAW264.7 cells. These findings reveal, in part, the molecular basis underlying the anti-inflammatory properties of moringa fruit extract.

scholarly journals Hydroxylumisterols, Photoproducts of Pre-Vitamin D3, Protect Human Keratinocytes against UVB-Induced Damage

2020 ◽  
Vol 21 (24) ◽  
pp. 9374 ◽  
Author(s):  
Anyamanee Chaiprasongsuk ◽  
Zorica Janjetovic ◽  
Tae-Kang Kim ◽  
Cynthia J. Schwartz ◽  
Robert C. Tuckey ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Inflammatory Responses ◽  
Human Keratinocytes ◽  
Inflammatory Activity ◽  
Orphan Receptors ◽  
Protein Levels ◽  
Tnf Α ◽  
Transglutaminase 1 ◽  
Anti Inflammatory ◽  
High Doses

Lumisterol (L3) is a stereoisomer of 7-dehydrocholesterol and is produced through the photochemical transformation of 7-dehydrocholesteol induced by high doses of UVB. L3 is enzymatically hydroxylated by CYP11A1, producing 20(OH)L3, 22(OH)L3, 20,22(OH)2L3, and 24(OH)L3. Hydroxylumisterols function as reverse agonists of the retinoic acid-related orphan receptors α and γ (RORα/γ) and can interact with the non-genomic binding site of the vitamin D receptor (VDR). These intracellular receptors are mediators of photoprotection and anti-inflammatory activity. In this study, we show that L3-hydroxyderivatives significantly increase the expression of VDR at the mRNA and protein levels in keratinocytes, both non-irradiated and after UVB irradiation. L3-hydroxyderivatives also altered mRNA and protein levels for RORα/γ in non-irradiated cells, while the expression was significantly decreased in UVB-irradiated cells. In UVB-irradiated keratinocytes, L3-hydroxyderivatives inhibited nuclear translocation of NFκB p65 by enhancing levels of IκBα in the cytosol. This anti-inflammatory activity mediated by L3-hydroxyderivatives through suppression of NFκB signaling resulted in the inhibition of the expression of UVB-induced inflammatory cytokines, including IL-17, IFN-γ, and TNF-α. The L3-hydroxyderivatives promoted differentiation of UVB-irradiated keratinocytes as determined from upregulation of the expression at the mRNA of involucrin (IVL), filaggrine (FLG), and keratin 14 (KRT14), downregulation of transglutaminase 1 (TGM1), keratins including KRT1, and KRT10, and stimulation of ILV expression at the protein level. We conclude that CYP11A1-derived hydroxylumisterols are promising photoprotective agents capable of suppressing UVB-induced inflammatory responses and restoring epidermal function through targeting the VDR and RORs.

scholarly journals Schisandra Chinensis Lignans Suppresses the Production of Inflammatory Mediators Regulated by NF-κB, AP-1, and IRF3 in Lipopolysaccharide-Stimulated RAW264.7 Cells

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3319 ◽  
Author(s):  
Gan Luo ◽  
Brian Cheng ◽  
Hui Zhao ◽  
Xiu-Qiong Fu ◽  
Ran Xie ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Nuclear Translocation ◽  
Chinese Herb ◽  
Underlying Mechanism ◽  
Raw264.7 Cells ◽  
Schisandra Chinensis ◽  
Protein Levels ◽  
Cytokines And Chemokines ◽  
Raw264.7 Macrophages ◽  
Anti Inflammatory

Schisandra Fructus (SF) is a traditional Chinese herb used in the treatment of inflammatory disorders like hepatitis. One of the main anti-inflammatory components of SF is the lignans. However, the underlying anti-inflammatory mechanism of Schisandra Chinensis lignans (SCL) remains unclear. This study aims to investigate the effects of SCL on inflammatory mediators in lipopolysaccharide-stimulated RAW264.7 cells and explore the underlying mechanism. The production of nitric oxide (NO) was determined by Griess reaction. ELISA was used to determine cytokine levels and chemokines secretion. To estimate protein levels and enzyme activities, we employed Western blotting. Nuclear localization of NF-κB, AP-1, and IRF3 was detected using immunofluorescence analyses. The results showed that SCL significantly reduced the release of inflammatory mediators, including NO and PGE2, which may be related to down-regulation of iNOS and COX-2 expression. The production of cytokines and chemokines was suppressed by SCL treatment. SCL also decreased the phosphorylation of IKKα/β, IκB-α, Akt, TBK1, ERK, p38, JNK, NF-κB (p65), AP-1 (c-Jun), and IRF3 in RAW264.7 macrophages activated with LPS. The nuclear protein levels and nuclear translocation of AP-1, NF-κB and IRF3 were suppressed by SCL. These results indicated that SCL suppressed the IKKα/β/NF-κB, MAPKs/AP-1 and TBK1/IRF3 signaling pathways in LPS-stimulated RAW264.7 macrophages.

scholarly journals Phenolic Compounds of Red Wine Aglianico del Vulture Modulate the Functional Activity of Macrophages via Inhibition of NF-κB and the Citrate Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Anna Santarsiero ◽  
Paolo Convertini ◽  
Antonio Vassallo ◽  
Valentina Santoro ◽  
Simona Todisco ◽  
...  
Keyword(s):  
Phenolic Compounds ◽  
Red Wine ◽  
Nuclear Translocation ◽  
Atp Citrate Lyase ◽  
Protein Levels ◽  
Metabolic Genes ◽  
Citrate Lyase ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine

Phenolic compounds of red wine powder (RWP) extracted from the Italian red wine Aglianico del Vulture have been investigated for the potential immunomodulatory and anti-inflammatory capacity on human macrophages. These compounds reduce the secretion of IL-1β, IL-6, and TNF-α proinflammatory cytokines and increase the release of IL-10 anti-inflammatory cytokine induced by lipopolysaccharide (LPS). In addition, RWP restores Annexin A1 levels, thus involving activation of proresolutive pathways. Noteworthy, RWP lowers NF-κB protein levels, promoter activity, and nuclear translocation. As a consequence of NF-κB inhibition, reduced promoter activities of SLC25A1—encoding the mitochondrial citrate carrier (CIC)—and ATP citrate lyase (ACLY) metabolic genes have been observed. CIC, ACLY, and citrate are components of the citrate pathway: in LPS-activated macrophages, the mitochondrial citrate is exported by CIC into the cytosol where it is cleaved by ACLY in oxaloacetate and acetyl-CoA, precursors for ROS, NO⋅, and PGE2 inflammatory mediators. We identify the citrate pathway as a RWP target in carrying out its anti-inflammatory activity since RWP reduces CIC and ACLY protein levels, ACLY enzymatic activity, the cytosolic citrate concentration, and in turn ROS, NO⋅, PGE2, and histone acetylation levels. Overall findings suggest that RWP potentially restores macrophage homeostasis by suppressing inflammatory pathways and activating proresolutive processes.

scholarly journals Enhanced Expression of Human Epididymis Protein 4 (HE4) Reflecting Pro-Inflammatory Status Is Regulated by CFTR in Cystic Fibrosis Bronchial Epithelial Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Zsolt Bene ◽  
Zsolt Fejes ◽  
Tibor Gabor Szanto ◽  
Ferenc Fenyvesi ◽  
Judit Váradi ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Nuclear Translocation ◽  
Patch Clamp Technique ◽  
Bronchial Epithelial ◽  
Human Epididymis Protein 4 ◽  
Protein Levels ◽  
Human Epididymis ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Cftr Modulators

Decreased human epididymis protein 4 (HE4) plasma levels were reported in cystic fibrosis (CF) patients under CFTR potentiator ivacaftor therapy, which inversely correlated with lung function improvement. In this study, we investigated whether HE4 expression was affected via modulation of CFTR function in CF bronchial epithelial (CFBE) cells in vitro. HE4 protein levels were measured in the supernatants of CFBE 41o− cells expressing F508del-CFTR or wild-type CFTR (wt-CFTR) after administration of lumacaftor/ivacaftor or tezacaftor/ivacaftor, while HE4 expression in CFBE 41o− cells were also analyzed following application of adenylate cyclase activators Forskolin/IBMX or CFTRinh172. The effect of all of these compounds on CFTR function was monitored by the whole-cell patch-clamp technique. Induced HE4 expression was studied with interleukin-6 (IL-6) in F508del-CFTR CFBE 41o− cells under TNF-α stimulation for 1 h up to 1 week in duration. In parallel, plasma HE4 was determined in CF subjects homozygous for p.Phe508del-CFTR mutation receiving lumacaftor/ivacaftor (Orkambi®) therapy. NF-κB-mediated signaling was observed via the nuclear translocation of p65 subunit by fluorescence microscopy together with the analysis of IL-6 expression by an immunoassay. In addition, HE4 expression was examined after NF-κB pathway inhibitor BAY 11-7082 treatment with or without CFTR modulators. CFTR modulators partially restored the activity of F508del-CFTR and reduced HE4 concentration was found in F508del-CFTR CFBE 41o− cells that was close to what we observed in CFBE 41o− cells with wt-CFTR. These data were in agreement with decreased plasma HE4 concentrations in CF patients treated with Orkambi®. Furthermore, CFTR inhibitor induced elevated HE4 levels, while CFTR activator Forskolin/IBMX downregulated HE4 in the cell cultures and these effects were more pronounced in the presence of CFTR modulators. Higher activation level of baseline and TNF-α stimulated NF-κB pathway was detected in F508del-CFTR vs. wt-CFTR CFBE 41o− cells that was substantially reduced by CFTR modulators based on lower p65 nuclear positivity and IL-6 levels. Finally, HE4 expression was upregulated by TNF-α with elevated IL-6, and both protein levels were suppressed by combined administration of NF-κB pathway inhibitor and CFTR modulators in CFBE 41o− cells. In conclusion, CFTR dysfunction contributes to abnormal HE4 expression via NF-κB in CF.

scholarly journals Tantalum Particles Induced Cytotoxic and Inflammatory Effects in Human Monocytes

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Yajie Yang ◽  
Yaokun Zhang ◽  
Yiyuan Kang ◽  
Chen Hu ◽  
Yanli Zhang ◽  
...  
Keyword(s):  
Human Monocyte ◽  
Cell Counting ◽  
Cytotoxicity Test ◽  
Protein Levels ◽  
Tnf Α ◽  
Factor Α ◽  
Extracellular Regulated Kinase ◽  
And Control ◽  
Necrosis Factor

The aim of this study is to evaluate the biological safety of tantalum (Ta) particles and to further explore the effects of Ta particles on human monocyte toxicity and inflammatory cytokine expression. Human monocyte leukemia (THP-1) cells were cultured with Ta and hydroxyapatite (HA) particles. Cell counting kit-8 method was used to evaluate the cytotoxicity of Ta and HA particles. The apoptosis effects were evaluated by flow cytometry, and the protein expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were evaluated by ELISA. The protein levels of inflammation-related signaling pathways including nuclear factor-kappa B (NF-κB) and extracellular regulated kinase (ERK) were detected by western blotting. The cytotoxicity test showed that the toxicity level of Ta in vitro was grade l, which is within the clinically acceptable range. Compared with the HA control, Ta had no significant effect on THP-1 cell apoptosis, IL-6, and TNF-α release. The phosphorylated levels of NF-κB and ERK at 3 h in the Ta group were lower than those in the HA and control groups ( P < 0.001 both). These results reveal Ta particles behave good biosafety properties and provide some new insights for the future clinical use of Ta.

Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells

2019 ◽  
Vol 16 (3) ◽  
pp. 251-260 ◽  
Author(s):  
Elaine Wan Ling Chan ◽  
Emilia Tze Ying Yeo ◽  
Kelly Wang Ling Wong ◽  
Mun Ling See ◽  
Ka Yan Wong ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Mrna Expression ◽  
Inflammatory Mediators ◽  
Beta Amyloid ◽  
Microglial Cells ◽  
Root Extracts ◽  
Tnf Α ◽  
P38α Mapk ◽  
Anti Inflammatory ◽  
Bv2 Microglial Cells

<P>Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments. Objective: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the production of pro-inflammatory mediators. Method: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay. Results: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators. Conclusions: These findings provided evidence that PS root extracts confer neuroprotection against Aβ- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer’s disease (AD).</P>

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