scholarly journals Amelioration of LPS-Induced Inflammation Response in Microglia by AMPK Activation

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Chin-Chen Chen ◽  
Jiun-Tsai Lin ◽  
Yi-Fang Cheng ◽  
Cheng-Yi Kuo ◽  
Chun-Fang Huang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Energy Homeostasis ◽  
Nuclear Translocation ◽  
Ampk Signaling ◽  
Neuroinflammatory Disease ◽  
Cellular Events ◽  
Compound C ◽  
Bv2 Cells ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Adenosine 5′-monophosphate-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis via modulating metabolism of glucose, lipid, and protein. In addition to energy modulation, AMPK has been demonstrated to associate with several important cellular events including inflammation. The results showed that ENERGI-F704 identified from bamboo shoot extract was nontoxic in concentrations up to 80 μM and dose-dependently induced phosphorylation of AMPK (Thr-172) in microglia BV2 cells. Our findings also showed that the treatment of BV2 with ENERGI-F704 ameliorated the LPS-induced elevation of IL-6 and TNF-αproduction. In addition, ENERGI-F704 reduced increased production of nitric oxide (NO) and prostaglandin E2 (PGE2) via downregulating the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2), respectively. Moreover, ENERGI-F704 decreased activated nuclear translocation and protein level of NF-κB. Inhibition of AMPK with compound C restored decreased NF-κB translocation by ENERGI-F704. In conclusion, ENERGI-F704 exerts inhibitory activity on LPS-induced inflammation through manipulating AMPK signaling and exhibits a potential therapeutic agent for neuroinflammatory disease.

Endoplasmic Reticulum Stress and NF-κB Pathway in Salidroside Mediated Neuroprotection: Potential of Salidroside in Neurodegenerative Diseases

2017 ◽  
Vol 45 (07) ◽  
pp. 1459-1475 ◽  
Author(s):  
Chenggui Wang ◽  
Yiting Lou ◽  
Jianxiang Xu ◽  
Zhenhua Feng ◽  
Yu Chen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Neurodegenerative Diseases ◽  
Microglia Activation ◽  
Phenylpropanoid Glycoside ◽  
Bv2 Cells ◽  
Protein Expressions ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Microglial activation leads to increased production of proinflammatory enzymes and cytokines, which is considered to play crucial role in neurodegenerative diseases, however there are only a few drugs that target microglia activation. Recent studies have indicated that the Traditional Chinese Medicine, salidroside (Sal), exerted anti-inflammatory effects. According to this evidence, our present study aims to explore the effect of the Sal (a phenylpropanoid glycoside compound which is isolated from rhodiola), on microglia activation in lipopolysaccharide (LPS)-stimulated BV-2 cells. Our results showed that Sal could significantly inhibit the excessive production of Nitric Oxide (NO) and Prostaglandin E2 (PGE2) in LPS-stimulated BV2 cells. Moreover, Sal treatment could suppress the mRNA and protein expressions of inflammatory enzymes, including Inducible Nitric Oxide Synthase (iNOS) and Cyclooxygenase-2 (COX-2). The mechanisms may be related to the inhibition of the activation of Nuclear Factor-kappaB (NF-[Formula: see text]B) and endoplasmic reticulum stress. Our study demonstrated that salidroside could inhibit lipopolysaccharide-induced microglia activation via the inhibition of the NF-[Formula: see text]B pathway and endoplasmic reticulum stress, which makes it a promising therapeutic agent for human neurodegenerative diseases.

A germacranolide sesquiterpene lactone suppressed inducible nitric oxide synthase by downregulating NF-κB activity

2011 ◽  
Vol 89 (3) ◽  
pp. 232-237 ◽  
Author(s):  
Hwa Jin Lee ◽  
Hyeyoun Jung ◽  
Junhye Kwon ◽  
Hua Li ◽  
Da Yeon Lee ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Sesquiterpene Lactone ◽  
P38 Mapk ◽  
Inducible Nitric Oxide Synthase ◽  
Nuclear Translocation ◽  
Inos Mrna ◽  
Oxide Synthase ◽  
Signal Cascades ◽  
Inducible Nitric Oxide

A germacranolide sesquiterpene lactone, 2α,5-epoxy-5,10-dihydroxy-6α-angeloyloxy-9β-(3-methylbutyloxy)-germacran-8α,12-olide (EDAG), isolated from Carpesium triste var. manshuricum , showed inhibitory activity in the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) mRNA and protein in LPS-activated macrophage cells. Molecular analysis reveals that these suppressive effects are correlated with the inhibition of NF-κB activation by EDAG. Immunoblotting showed that EDAG suppressed the LPS-induced degradation of I-κBα and decreased nuclear translocation of p65. Futhermore, EDAG showed reduced phosphorylation of ERK1/2 and p38 MAPK, whereas activation of JNK was not changed. These data suggest, at least in part, that EDAG utilizes the signal cascades of ERK1/2, p38 MAPK, and NF-κB for the suppression of iNOS gene expression.

Resveratrol inhibition of inducible nitric oxide synthase in skeletal muscle involves AMPK but not SIRT1

2011 ◽  
Vol 301 (5) ◽  
pp. E922-E930 ◽  
Author(s):  
Carolina Centeno-Baez ◽  
Patrice Dallaire ◽  
André Marette
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
No Production ◽  
Compound C ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide ◽  
L6 Myocytes ◽  
Inos Induction

The plant-derived polyphenol resveratrol (RSV) modulates life span and metabolism, and it is thought that these effects are largely mediated by activating the deacetylase enzyme SIRT1. However, RSV also activates the cell energy sensor AMP-activated protein kinase (AMPK). We have previously reported that AMPK activators inhibit inducible nitric oxide synthase (iNOS), a key proinflammatory mediator of insulin resistance in endotoxemia and obesity. The aim of this study was to evaluate whether RSV inhibits iNOS induction in insulin target tissues and to determine the role of SIRT1 and AMPK activation in this effect. We found that RSV (40 mg/kg ip) treatment decreased iNOS induction and NO production in skeletal muscle and white adipose tissue, but not in liver, of endotoxin (LPS)-challenged mice. This effect of the polyphenol was recapitulated in vitro, where RSV (10–80 μM) robustly inhibited iNOS protein induction and NO production in cytokine/LPS-treated L6 myocytes and 3T3-L1 adipocytes. However, no effect of RSV was observed on iNOS induction in FAO hepatocytes. Further studies using inhibitors of SIRT1 revealed that the deacetylase enzyme is not involved in RSV action on iNOS. In marked contrast, RSV activates AMPK in L6 myocytes, and blunting its activation using Compound C or RNA interference partly blocked the inhibitory effect of RSV on NO production. These results show that RSV specifically inhibits iNOS induction in muscle through a mechanism involving AMPK but not SIRT1 activation. This anti-inflammatory action of RSV likely contributes to the therapeutic effect of this plant polyphenol.

scholarly journals Anti-Inflammatory Activity of Three Triterpene from Hippophae rhamnoides L. in Lipopolysaccharide-Stimulated RAW264.7 Cells

2021 ◽  
Vol 22 (21) ◽  
pp. 12009
Author(s):  
Yu Han ◽  
Chen Yuan ◽  
Xiaowei Zhou ◽  
Yingjie Han ◽  
Yanhao He ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nuclear Translocation ◽  
Raw264.7 Cells ◽  
Asiatic Acid ◽  
Inflammatory Factor ◽  
Maslinic Acid ◽  
Anti Inflammatory ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Oleanolic acid (OA), asiatic acid (AA), and maslinic acid (MA) are ubiquitous isomeric triterpene phytochemicals with many pharmacological effects. To improve their application value, we used lipopolysaccharide (LPS) to induce RAW264.7 cells and studied the differences in the anti-inflammatory effects of the triterpenes according to their structural differences. MTT, Griess, and immunofluorescence assays, ELISA, flow cytometry, and Western blotting, were performed. The release of LPS-induced pro-inflammatory mediators, such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), and interleukin (IL-6), was significantly inhibited by OA, AA, and MA at the same concentration, and AA and MA promoted the production of anti-inflammatory factor IL-10. OA, AA, and MA inhibited LPS-induced NF-κB nuclear translocation in RAW264.7 cells. OA and AA inhibited the phosphorylation of ERK1/2, P38, and JNK1/2 in LPS-stimulated RAW264.7 cells. Moreover, OA increased LPS-induced Nrf2 expression and decreased Keap1 expression in RAW264.7 cells. OA, AA, and MA inhibited LPS-stimulated intracellular reactive oxygen species (ROS) production and alleviated mitochondrial membrane potential depletion. Overall, our data suggested that OA, AA, and MA exhibited significant anti-inflammatory effects in vitro. In particular, OA and AA take effects through the MAPKs, NF-κB, and Nrf2 signaling pathways.

Suffrutines A and B Inhibit the Expression of Inflammatory Mediators in LPS-Induced RAW264.7 Cells by Suppressing the NF-κB Signaling Pathway

Planta Medica ◽  
2021 ◽  
Author(s):  
Chun Chen ◽  
Ze-Feng Zhu ◽  
Wen-Xing Nie ◽  
Yong Zou
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Mediators ◽  
Nuclear Translocation ◽  
Nuclear Factor Κb ◽  
Inhibitory Effect ◽  
Raw264.7 Cells ◽  
Indolizidine Alkaloids ◽  
Oxide Synthase ◽  
Potent Inhibitory Activity ◽  
Inducible Nitric Oxide

Abstract Flueggea suffruticosa is a traditional Chinese medicine that has been commonly used for the treatment of inflammatory ailments, including rheumatism and lumbago. Suffrutines A and suffrutines B are a pair of novel E,E and Z,E isomeric indolizidine alkaloids isolated from the roots of F. suffruticosa. However, their anti-inflammatory activity has not been reported thus far. The aim of this study was to investigate the inhibitory effect of inflammatory mediators and possible mechanisms of suffrutines A and B in lipopolysaccharide-induced RAW264.7 cells. Results showed that suffrutines A and B could remarkably inhibit the production of nitric oxide, prostaglandin E2, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 in lipopolysaccharide-induced RAW264.7 cells. Further evaluation demonstrated that compared with suffrutines A, suffrutines B could more significantly inhibit the phosphorylation of IKKα/β, the degradation of IκBα, and the nuclear translocation of the p65 and p52 subunits in the canonical and non-canonical nuclear factor-κB pathways. Therefore, suffrutines B exhibited more potent inhibitory activity on inflammatory mediators than suffrutines A.

scholarly journals Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding

Blood ◽  
2006 ◽  
Vol 108 (2) ◽  
pp. 518-524 ◽  
Author(s):  
Wu-Guo Deng ◽  
Shao-Tzu Tang ◽  
Hui-Ping Tseng ◽  
Kenneth K. Wu
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Nuclear Translocation ◽  
Cyclooxygenase 2 ◽  
Raw 264.7 Cells ◽  
Dependent Manner ◽  
Cox 2 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Melatonin has been shown to be produced by nonpineal cells and possess anti-inflammatory actions in animal models. In the present study, we tested the hypothesis that melatonin suppresses the expression of proinflammatory genes such as cyclooxygenase-2 (COX2) and inducible nitric oxide synthase (INOS) by a common transcriptional mechanism. Melatonin but not tryptophan or serotonin inhibited lipopolysaccharide (LPS)–induced COX-2 and iNOS protein levels and promoter activities in RAW 264.7 cells in a time- and concentration-dependent manner. LPS or LPS plus interferon-γ (IFNγ) increased binding of all 5 isoforms of NF-κB to COX-2 and iNOS promoters. Melatonin selectively inhibited p52 binding without affecting p100 expression, p52 generation from p100, or p52 nuclear translocation. p52 acetylation was enhanced by LPS, which was abrogated by melatonin. Melatonin inhibited p300 histone acetyltransferase (HAT) activity and abrogated p300-augmented COX-2 and iNOS expression. HAT inhibitors suppressed LPS-induced p52 binding and acetylation to an extent similar to melatonin, and melatonin did not potentiate the effect of HAT inhibitors. These results suggest that melatonin inhibits COX-2 and iNOS transcriptional activation by inhibiting p300 HAT activity, thereby suppressing p52 acetylation, binding, and transactivation.

Sign in / Sign up

Export Citation Format

Share Document