scholarly journals Preliminary Study on the In vivo Anti-neuroinflammatory Effects of Khaya grandifoliola and Cymbopogon citratus Polysaccharide Fractions

2020 ◽  
pp. 23-32
Author(s):  
K. F. Mediesse ◽  
G. Matharasala ◽  
T. Boudjeko ◽  
P. Yogeeswari
Keyword(s):  
Thermal Hyperalgesia ◽  
Test Dose ◽  
Nuclear Factor Κb ◽  
Stem Bark ◽  
Brain Inflammation ◽  
Tail Flick ◽  
Cymbopogon Citratus ◽  
Luminex Assay ◽  
Tnf Α

Aims: To determine the effects of polysaccharide fractions named KGF and CCF respectively for Khaya grandifoliola stem bark and Cymbopogon citratus leaves on Central Nervous System (CNS) depression and on systemic lipopolysaccharide (LPS)-induced brain inflammation and hyperalgesia in BALB/c. Methodology: BALB/c mice weighing about 25-35 g were used for the experimentation. Depressant effects of polysaccharide fractions were firstly evaluated using Rota Rod and Actophotometer apparatus. Secondly, LPS or saline solution (5 mg/kg) was Intraperitoneally administered (i.p.) 1 hour after oral administration of polysaccharide fractions (100 mg/kg test dose, p.o.) or distilledwater. Then, the hot plate and tail-flick models were performed 1 hour after LPS injection to determine thermal hyperalgesia and brain inflammation, was examined 3 hours after LPS injection by Luminex assay. Results:Systemic LPS administration resulted in a reduction of pain response latency and an increasing expression of nuclear factor-κB (NF-κB) and pro-inflammatory cytokines interleukin-1β (IL-1β), IL-6, tumor necrosis factor- α (TNF-α) genes in brain after 24 hours. From the results it was observed that treatment with KGF and CCF (100 mg/kg, p.o) significantly attenuated LPS-induced hyperalgesia and overexpression of brain levels of IL-1β, IL-6 and TNF-α genes dependent on inhibition of the NF-κB signaling pathway in BALB/c without CNS depressant properties. Conclusion: The present findings confirm the potential of KGF and CCF in the treatment of neuroinflammation-related diseases and it warrant further testing for the development of a new chemical entities. However further studies are required for determination of effective dose and mechanism of action associated.

Lipopolysaccharide regulates proinflammatory cytokine expression in mouse myoblasts and skeletal muscle

2002 ◽  
Vol 283 (3) ◽  
pp. R698-R709 ◽  
Author(s):  
Robert A. Frost ◽  
Gerald J. Nystrom ◽  
Charles H. Lang
Keyword(s):  
Skeletal Muscle ◽  
Cell Wall ◽  
Mrna Expression ◽  
Nuclear Factor Κb ◽  
Cytokine Expression ◽  
Mrna Accumulation ◽  
C2c12 Myoblasts ◽  
Tnf Α ◽  
Mrna Content

The purpose of the present study was to examine the regulation of tumor necrosis factor (TNF)-α and interleukin (IL)-6 by lipopolysaccharide (LPS) in C2C12 myoblasts and mouse skeletal muscle. LPS produced dose- and time-dependent increases in TNF-α and IL-6 mRNA content in C2C12 myoblasts. The LPS-induced cytokine response could be mimicked by peptidoglycan from the cell wall of Staphylococcus aureus but not by zymosan A, a cell wall component from Saccharomyces cerevisiae. Ongoing protein synthesis was not necessary for the increase in the two cytokine mRNAs. The transcriptional inhibitor 5,6-dichloro-β-d-ribofuranosyl-benzimidazole blocked LPS-stimulated IL-6 mRNA expression without changing its mRNA half-life. The anti-inflammatory glucocorticoid dexamethasone selectively blocked LPS-stimulated IL-6 mRNA accumulation but not TNF-α. In contrast, the proteasomal inhibitor MG-132 blocked TNF-α mRNA expression but not IL-6. Exposure of myoblasts to LPS was associated with a rapid decrease in the inhibitor of nuclear factor-κB (I κB, α, and ε), and this response was also blocked by MG-132. Treatment of myocytes with IL-1 or TNF-α also increased IL-6 mRNA content, but the increase in IL-6 mRNA due to LPS could not be prevented by pretreatment with antagonists to either IL-1 or TNF. Under in vivo conditions, LPS increased the plasma concentration of TNF-α and IL-6 and stimulated the accumulation of their mRNAs in multiple tissues including skeletal muscle from wild-type mice. In contrast, the ability of LPS to stimulate the same cytokines was markedly decreased in mice that harbor a mutation in the Toll-like receptor 4. Our data suggest that LPS stimulates cytokine expression not only in classical immune tissues but also in skeletal muscle.

Regulation of granulocyte apoptosis by NF-κB

2004 ◽  
Vol 32 (3) ◽  
pp. 465-467 ◽  
Author(s):  
C. Ward ◽  
A. Walker ◽  
I. Dransfield ◽  
C. Haslett ◽  
A.G. Rossi
Keyword(s):  
Nuclear Factor Κb ◽  
Resolution Of Inflammation ◽  
Tnf Α ◽  
Successful Resolution ◽  
Factor Α ◽  
Apoptotic Effects ◽  
Second Wave ◽  
Crucial Part

Granulocyte apoptosis is a crucial part of the successful resolution of inflammation. In vitro results show that activation of NF-κB (nuclear factor κB) in granulocytes is a survival mechanism. NF-κB inhibitors increase the rate of constitutive apoptosis in neutrophils and eosinophils and cause these cells to respond to the pro-apoptotic effects of TNF-α (tumour necrosis factor-α). Results from both in vivo and in vitro experiments suggest that there are at least two important waves of NF-κB activation in inflammatory loci, which increase the expression of COX-2 (cyclooxygenase-2), itself an NF-κB controlled gene. The first wave causes the production of inflammatory mediators such as PGE2 (prostaglandin E2), allowing the establishment of inflammation. The second wave causes the synthesis of PGD2 and its metabolites that induce granulocyte apoptosis by inhibiting NF-κB activation. These metabolites may therefore be important physiological mediators controlling the resolution of inflammation. Although NF-κB is an important target for anti-inflammatory therapy, the timing of inhibition in vivo may be crucial, to ensure that production of PGD2 and its sequential metabolites can occur.

scholarly journals Protocatechuic acid as an inhibitor of the JNK/CXCL1/CXCR2 pathway relieves neuropathic pain in CCI rats

2021 ◽  
Author(s):  
Hong-xia Chang ◽  
Yue-feng Zhao
Keyword(s):  
Neuropathic Pain ◽  
Sciatic Nerve ◽  
Satellite Cells ◽  
Protocatechuic Acid ◽  
Thermal Hyperalgesia ◽  
Tnf Α ◽  
Chemokine Ligand ◽  
New Perspective

Emerging evidence has shown that protocatechuic acid (PCA) has antioxidant and anti-inflammatory effects. Evidence suggests that PCA can alleviate the injury of sciatic nerve, while the mechanism of its therapeutic effect on neuralgia remains unknown.         Chromium bowel ligation was used in vivo to establish a chronic constriction injury (CCI) rat model to induce sciatic nerve pain. Subsequently, two doses of PCA were used to treat CCI rats. In vitro, 10 ng/mL TNF-α was used to stimulate glial satellite cells derived from the dorsal root ganglia (DRG) L4-L6 of the sciatic nerve to simulate sciatic nerve pain. PCA relieved mechanical allodynia and thermal hyperalgesia in CCI rats. CCK-8 assay revealed that PCA inhibited the proliferation of glial satellite cells induced by TNF-α. Moreover, ELISA demonstrated that PCA could improve the inflammatory response of rats caused by CCI and cells induced by TNF-α. Next, RT-qPCR and Western blot assays showed that PCA blocked the c-Jun N-terminal kinase/the chemokine ligand 1/CXC chemokine receptor 2 (JNK/CXCL1/CXCR2) pathway by inhibiting CXCL1 levels in cells induced by TNF-α and DRG in CCI rats. In conclusion, PCA can alleviate neuropathic pain in CCI rats and improve oxidative stress by inhibiting the JNK/CXCL1/CXCR2 signaling pathway. Thus, these findings provide a new perspective for the treatment of neuropathic pain caused by CCI.

scholarly journals Tau activates microglia via the PQBP1-cGAS-STING pathway to promote brain inflammation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Meihua Jin ◽  
Hiroki Shiwaku ◽  
Hikari Tanaka ◽  
Takayuki Obita ◽  
Sakurako Ohuchi ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Direct Interaction ◽  
Nuclear Factor Κb ◽  
Brain Inflammation ◽  
Immunodeficiency Virus ◽  
Intracellular Receptor ◽  
Disease Protein ◽  
Sting Pathway

AbstractBrain inflammation generally accompanies and accelerates neurodegeneration. Here we report a microglial mechanism in which polyglutamine binding protein 1 (PQBP1) senses extrinsic tau 3R/4R proteins by direct interaction and triggers an innate immune response by activating a cyclic GMP-AMP synthase (cGAS)-Stimulator of interferon genes (STING) pathway. Tamoxifen-inducible and microglia-specific depletion of PQBP1 in primary culture in vitro and mouse brain in vivo shows that PQBP1 is essential for sensing-tau to induce nuclear translocation of nuclear factor κB (NFκB), NFκB-dependent transcription of inflammation genes, brain inflammation in vivo, and eventually mouse cognitive impairment. Collectively, PQBP1 is an intracellular receptor in the cGAS-STING pathway not only for cDNA of human immunodeficiency virus (HIV) but also for the transmissible neurodegenerative disease protein tau. This study characterises a mechanism of brain inflammation that is common to virus infection and neurodegenerative disorders.

In vivo anti-inflammatory action of eugenol on lipopolysaccharide-induced lung injury

2010 ◽  
Vol 108 (4) ◽  
pp. 845-851 ◽  
Author(s):  
Clarissa B. Magalhães ◽  
Douglas R. Riva ◽  
Leonardo J. DePaula ◽  
Aline Brando-Lima ◽  
Vera Lúcia G. Koatz ◽  
...  
Keyword(s):  
Lung Injury ◽  
Lavage Fluid ◽  
Nuclear Factor Κb ◽  
Tissue Expression ◽  
The Other ◽  
Alveolar Collapse ◽  
Tnf Α ◽  
Anti Inflammatory ◽  
Inflammatory Action

Eugenol, a methoxyphenol component of clove oil, suppresses cyclooxygenase-2 expression, while eugenol dimers prevent nuclear factor-κB (NF-κB) activation and inflammatory cytokine expression in lipopolysaccharide-stimulated macrophages. Our aim was to examine the in vivo anti-inflammatory effects of eugenol. BALB/c mice were divided into four groups. Mice received saline [0.05 ml intratracheally (it), control (Ctrl) and eugenol (Eug) groups] or Escherichia coli LPS (10 μg it, LPS and LPSEug groups). After 6 h, mice received saline (0.2 ml ip, Ctrl and LPS groups) or eugenol (160 mg/kg ip, Eug and LPSEug groups). Twenty-four hours after LPS injection, pulmonary resistive (ΔP1) and viscoelastic (ΔP2) pressures, static elastance (Est), and viscoelastic component of elastance (ΔE) were measured. Lungs were prepared for histology. In parallel mice, bronchoalveolar lavage fluid was collected 24 h after LPS injection. TNF-α was determined by ELISA. Lung tissue expression of NF-κB was determined by EMSA. ΔP1, ΔP2, Est, and ΔE were significantly higher in the LPS group than in the other groups. LPS mice also showed significantly more alveolar collapse, collagen fibers, and neutrophil influx and higher TNF-α levels and NF-κB expression than the other groups. Eugenol treatment reduced LPS-induced lung inflammation, improving lung function. Our results suggest that eugenol exhibits in vivo anti-inflammatory action in LPS-induced lung injury.

scholarly journals Glutathione S-transferases: unexpected roles in astrocyte activation and astrocyte-microglia communication during brain inflammation

2017 ◽  
Author(s):  
Shin-ichi Kano ◽  
Eric Y. Choi ◽  
Eisuke Dohi ◽  
Indigo V. L. Rose ◽  
Daniel J. Chang ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Microglia Activation ◽  
Brain Inflammation ◽  
Astrocyte Activation ◽  
Systemic Injection ◽  
Mutual Regulation

AbstractAstrocytes and microglia play critical roles in brain inflammation, but their mutual regulation is not fully understood. Here we report unexpected roles for glutathione S-transferases (GSTs), particularly GSTM1, in astrocyte activation and astrocyte-mediated enhancement of microglia activation during brain inflammation. We found that astrocyte-specific silencing of GSTM1 expression in the prefrontal cortex (PFC) attenuated microglia activation in brain inflammation induced by systemic injection of lipopolysaccharides (LPS). Gstm1 silencing in astrocytes also attenuated LPS-induced TNF-α production by microglia in co-culture. In astrocytes, GSTM1 was required for the activation of nuclear factor-κB (NF-κB) and c-Jun N-terminal kinases (JNK) and the production of pro-inflammatory mediators previously implicated in microglia activation, such as granulocyte-macrophage colony-stimulating factor (GM-CSF/CSF2) and chemokine (C-C motif) ligand 2 (CCL2). Similar results were also obtained with GSTT2 both in vitro and in vivo. Thus, our study identified a critical role for GSTs in priming astrocytes and enhancing microglia activation during brain inflammation.Significant StatementAstrocytes and microglia play critical roles in brain inflammation, but it is not fully understood how astrocytes regulate microglia activation. Here we report a novel mechanism by which glutathione S-transferases (GSTs), the enzymes for phase II detoxification of xenobiotic metabolism, in astrocytes control microglia activation during brain inflammation. We found that GSTs, particularly GSTM1, regulate the induction of pro-inflammatory mediators via the activation of NF-κB and JNK in astrocytes. Our studies provide evidence that GST enzymes are active players in brain inflammation and can be targeted to regulate microglia activation.

scholarly journals Nobiletin alleviates endometriosis via down-regulating NF-κB activity in endometriosis mouse model

2018 ◽  
Vol 38 (3) ◽  
Author(s):  
Xin Wei ◽  
Xu Shao
Keyword(s):  
Mouse Model ◽  
Nuclear Factor Κb ◽  
Lesion Size ◽  
Luciferase Assay ◽  
Nuclear Antigen ◽  
Proinflammatory Mediators ◽  
Activation Of Transcription ◽  
Tnf Α ◽  
E Cadherin

Nobiletin exhibits protective potential on inflammation and inhibits the activation of transcription factors nuclear factor-κB (NF-κB). However, its effects on the progression of endometriosis remain unsettled. The present study aimed to explore the in vivo alleviation of nobiletin on endometriosis and its mechanism of action. The mouse model of endometriosis was established and administered with nobiletin. The ectopic lesion size was measured and the hotplate test was performed to assess the amelioration of nobiletin on endometriosis. The expression of proliferation and angiogenesis relevant genes including proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and E-cadherin was measured by immunostaining and the mRNA expression of proinflammatory mediators including interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, matrix metalloproteinases (MMP)-1, and MMP-3 was measured by RT-PCR. The change of NF-κB activity in endometriotic cells was evaluated by Western blotting and confirmed by luciferase assay. Administration of nobiletin significantly reduced lesions size and pain in endometriosis mice. Nobiletin significantly altered the expression of PCNA, VEGF, and E-cadherin in ectopic endometrium, as well as the levels of IL-6, IL-1β, TNF-α, MMP-1, and MMP-3. Nobiletin also showed remarkably impairment on the activation of NF-κB in promoting endometriotic cells, likely targeting on the activity of IκB kinases (IKKs). The present study provides the first evidence that nobiletin exerts protection on endometriosis via inhibition the activation of NF-κB, specifically on the activity of IκB kinases.

scholarly journals ApoE deficiency promotes colon inflammation and enhances the inflammatory potential of oxidized-LDL and TNF-α in primary colon epithelial cells

2016 ◽  
Vol 36 (5) ◽  
Author(s):  
Ali H. El-Bahrawy ◽  
Abdelmetalab Tarhuni ◽  
Hogyoung Kim ◽  
Venkat Subramaniam ◽  
Ilyes Benslimane ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Map Kinases ◽  
Oxidized Ldl ◽  
Nuclear Factor Κb ◽  
Inflammatory Factors ◽  
Moderate Increase ◽  
Tnf Α ◽  
Cox 2

Although deficiency in Apolipoprotein E (ApoE) is linked to many diseases, its effect on colon homoeostasis remains unknown. ApoE appears to control inflammation by regulating nuclear factor-κB (NF-κB). The present study was designed to examine whether ApoE deficiency affects factors of colon integrity in vivo and given the likelihood that ApoE deficiency increases oxidized lipids and TNF-α, the present study also examined whether such deficiency enhances the inflammatory potential of oxidized-LDL (oxLDL) and TNF-α in colon epithelial cells (CECs), in vitro. Here we show that ApoE deficiency is associated with chronic inflammation systemically and in colonic tissues as assessed by TNF-α levels. Increased colon TNF-α mRNA coincided with a substantial increase in cyclooxygenase (COX)-2. ApoE deficiency enhanced the potential of oxLDL and TNF-α to induce COX-2 expression as well as several other inflammatory factors in primary CECs. Interestingly, oxLDL enhanced TGF-β expression only in ApoE−/−, but not in wild-type, epithelial cells. ApoE deficiency appears to promote COX-2 expression enhancement through a mechanism that involves persistent NF-κB nuclear localization and PI3 and p38 MAP kinases but independently of Src. In mice, ApoE deficiency promoted a moderate increase in crypt length, which was associated with opposing effects of an increase in cell proliferation and apoptosis at the bottom and top of the crypt respectively. Our results support the notion that ApoE plays a central role in colon homoeostasis and that ApoE deficiency may constitute a risk factor for colon pathologies.

Withanolides from Withania somnifera Ameliorate Neutrophil Infiltration in Endotoxin-Induced Peritonitis by Regulating Oxidative Stress and Inflammatory Cytokines

Planta Medica ◽  
2021 ◽  
Author(s):  
Siva Kumar Solleti ◽  
Hoshiyar Singh ◽  
Acharya Balkrishna ◽  
Niti Sharma ◽  
Anurag Varshney
Keyword(s):  
Oxidative Stress ◽  
Withania Somnifera ◽  
Neutrophil Infiltration ◽  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Activator Protein 1 ◽  
Pharmacological Effects ◽  
Root Extracts ◽  
Tnf Α

AbstractIdentification of novel anti-inflammatory strategies are needed to avoid the side effects associated with the currently available therapies. Use of anti-inflammatory herbal remedies is gaining attention. The purpose of the present investigation was to evaluate the pharmacological potential of the withanolide-rich root extracts of the medical plant Withania somnifera (L.) Dunal using in vivo and in vitro models of endotoxin-induced inflammation and oxidative stress. The pharmacological effects of W. somnifera root extracts were evaluated using a mouse model of endotoxin (lipopolysaccharide)-induced peritonitis and various relevant human cell lines. HPLC analysis of the W. somnifera root extracts identified the presence of various bioactive withanolides. In vivo challenge of mice with endotoxin resulted in the infiltration of various leukocytes, specifically neutrophils, along with monocytes and lymphocytes into the peritoneal cavity. Importantly, prophylactic treatment with W. somnifera inhibited the migration of neutrophils, lymphocytes, and monocytes and decreased the release of interleukin-1β, TNF-α, and interleukin-6 cytokines into the peritoneal cavity as identified by ELISA. Liver (glutathione peroxidase, glutathione, glutathione disulfide, superoxide dismutase, malondialdehyde, myeloperoxidase) and peritoneal fluid (nitrite) biochemical analysis revealed the antioxidant profile of W. somnifera. Similarly, in human HepG2 cells, W. somnifera significantly modulated the antioxidant levels. In THP-1 cells, W. somnifera decreased the secretion of interleukin-6 and TNF-α. In HEK-Blue reporter cells, W. somnifera inhibited TNF-α-induced nuclear factor-κB/activator protein 1 transcriptional activity. Our findings suggest the pharmacological effects of root extracts of W. somnifera rich in withanolides inhibit neutrophil infiltration, oxidative hepatic damage, and cytokine secretion via modulating the nuclear factor-κB/activator protein 1 pathway.

scholarly journals Regulation of Toll-like receptor–mediated inflammatory response by complement in vivo

Blood ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 228-236 ◽  
Author(s):  
Xinhua Zhang ◽  
Yuko Kimura ◽  
Chongyun Fang ◽  
Lin Zhou ◽  
Georgia Sfyroera ◽  
...  
Keyword(s):  
Cytokine Production ◽  
Nuclear Factor Κb ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Tlr Signaling ◽  
Tnf Α ◽  
Mitogen Activated Protein ◽  
Factor Α ◽  
Molecular Patterns

Toll-like receptors (TLRs) and complement are 2 components of innate immunity that are critical for first-line host defense and elicitation of adaptive immune responses. Many pathogen-associated molecular patterns activate both TLR and complement, but whether and how these 2 systems, when coactivated in vivo, interact with each other has not been well studied. We demonstrate here a widespread regulation of TLR signaling by complement in vivo. The TLR ligands lipopolysacharride (TLR4), zymosan (TLR2/6), and CpG oligonucleotide (TLR9) caused, in a complement-dependent manner, strikingly elevated plasma interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1β, and/or decreased plasma IL-12 levels in mice deficient in the membrane complement inhibitor decay-accelerating factor (DAF). A similar outcome was observed in wild-type mice cotreated with the TLR ligands and cobra venom factor, a potent complement activator. The regulatory effect of complement on TLR-induced cytokine production in vivo was mediated by the anaphylatoxin receptors C5aR and C3aR. Additionally, changes in lipopolysaccharide (LPS)–induced cytokine production in DAF-deficient mice correlated with increased mitogen-activated protein kinase and nuclear factor-κB activation in the spleen. These results reveal a strong interaction between complement and TLR signaling in vivo and suggest a novel mechanism by which complement promotes inflammation and modulates adaptive immunity.

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