Ferulic Acid Reduces Cerebral Infarct Through Its Antioxidative and Anti-Inflammatory Effects Following Transient Focal Cerebral Ischemia in Rats

2008 ◽  
Vol 36 (06) ◽  
pp. 1105-1119 ◽  
Author(s):  
Chin-Yi Cheng ◽  
Tin-Yun Ho ◽  
E.-Jian Lee ◽  
Shan-Yu Su ◽  
Nou-Ying Tang ◽  
...  
Keyword(s):  
Ferulic Acid ◽  
Neurological Deficit ◽  
Focal Cerebral Ischemia ◽  
Nuclear Factor Κb ◽  
Cerebral Infarct ◽  
Superoxide Radicals ◽  
Neurological Deficits ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Neurological Deficit Score

Both Angelica sinensis (Oliv.) Diels (AS) and Ligusticum chuanxiong Hort. (LC) have been used to treat stroke in traditional Chinese medicine for centuries. Ferulic acid (FA), a component in both AS and LC, plays a role in neuroprotection. The purpose of this study was to investigate the effects of FA on cerebral infarct and the involvement of neuroprotective pathway. Rats underwent 2 hours and 24 hours of reperfusion after 90 min middle cerebral artery occlusion (MCAo). The cerebral infarct and neurological deficits were measured after 24 hours of reperfusion. Furthermore, the expression of superoxide radicals, intercellular adhesion molecule-1 (ICAM-1), myeloperoxidase (MPO), nuclear factor-κB (NF-κB) immunoreactive cells were assessed after 2 hours and 24 hours of reperfusion. Administration of 80 and 100 mg/kg of FA at the beginning of MCAo significantly reduced cerebral infarct and neurological deficit-score, similar results were obtained by 100 mg/kg of FA administered 30 min after MCAo. FA treatment (100 mg/kg i.v.) effectively suppressed superoxide radicals in the parenchyma lesion, and ICAM-1 immunoreactive vessels in the ischemic striatum after 2 hours of reperfusion. FA (100 mg/kg i.v.) reduced the expression of ICAM-1 and NF-κB in the ischemic cortex and striatum, also down-regulated MPO immunoreactive cells in the ischemic cortex after 24 hours of reperfusion. These results showed that the effect of FA on reducing cerebral infarct area and neurological deficit-score were at least partially attributed to the inhibition of superoxide radicals, ICAM-1 and NF-κB expression in transient MCAo rats.

Inhaled nitric oxide protects against hyperoxia-induced apoptosis in rat lungs

1999 ◽  
Vol 277 (3) ◽  
pp. L596-L605 ◽  
Author(s):  
Clare E. Howlett ◽  
James S. Hutchison ◽  
John P. Veinot ◽  
Aaron Chiu ◽  
Pradeep Merchant ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nuclear Factor Κb ◽  
Inhaled Nitric Oxide ◽  
Intercellular Adhesion Molecule ◽  
Activator Protein 1 ◽  
Intercellular Adhesion Molecule 1 ◽  
Vascular Leak ◽  
Induced Apoptosis ◽  
Apoptosis And Inflammation ◽  
First Time

Inhaled nitric oxide (NO), frequently administered in combination with hyperoxic gas mixtures, was recently shown to protect against the injurious consequences of prolonged hyperoxia. We investigated the possibility that this protective effect is attributable to the ability of NO to block pulmonary apoptosis. We show that rats exposed to 100% O2for 60 h develop severe lung injury consisting of pronounced vascular leak and alveolar apoptosis as inferred from the presence of positive terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling and DNA ladders in agarose gels and a decrease in constitutive procaspase-3 levels. However, the inclusion of NO (20 parts/million) in the hyperoxic gas mixture significantly attenuated both the vascular leak and apoptosis. NO reversed the hyperoxia-associated changes in the activity of the redox-sensitive transcription factors nuclear factor-κB, activator protein-1, and Sp1 after 24 h, lowered intercellular adhesion molecule-1 levels, and increased glutathione content. We therefore show, for the first time, that NO can protect against both hyperoxia-induced apoptosis and inflammation. The data suggest that this protection may occur at the transcriptional and caspase-activation levels.

scholarly journals Resveratrol prevents TNF-α-induced VCAM-1 and ICAM-1 upregulation in endothelial progenitor cells via reduction of NF-κB activation

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094513
Author(s):  
Yefei Zhang ◽  
Huahua Liu ◽  
Weiliang Tang ◽  
Qiongya Qiu ◽  
Jiahao Peng
Keyword(s):  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Adhesion Molecule ◽  
Nuclear Factor Κb ◽  
Intercellular Adhesion Molecule ◽  
Adhesion Assay ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Progenitor ◽  
Tnf Α ◽  
Factor Α

Objective To assess the effects of resveratrol (RSV) on expression of adhesion molecules in endothelial progenitor cells (EPCs) following tumor necrosis factor-α (TNF-α) stimulation. Methods EPCs were treated with RSV and stimulated with TNF-α. A mononuclear cell (MNC) adhesion assay was used to assess the effects of RSV on TNF-α-induced MNC adhesion. Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and E-selectin expression levels and nuclear factor κB (NF-κB) activation were assessed by immunoblotting. Results MNC adhesion to TNF-α-treated EPCs and VCAM-1/ICAM-1/E-selectin levels in EPCs were increased following TNF-α stimulation and decreased following RSV treatment. TNF-α enhanced NF-κB inhibitor α (IκB-α) phosphorylation in the cytosol as well as nuclear NF-κB p65 levels, both of which were decreased by RSV. Conclusions These findings provide new insights into RSV’s anti-inflammatory and anti-atherosclerotic effects. RSV’s mechanism of action might involve downregulation of VCAM-1, ICAM-1 and E-selectin by partial blockade of TNF-α-induced NF-κB activation and IκB-α phosphorylation in EPCs.

scholarly journals Neurochemical Mechanism of Electroacupuncture: Anti-Injury Effect on Cerebral Function after Focal Cerebral Ischemia in Rats

2009 ◽  
Vol 6 (1) ◽  
pp. 51-56 ◽  
Author(s):  
Shubo Zhong ◽  
Zhongren Li ◽  
Lianjin Huan ◽  
Bo-Ying Chen
Keyword(s):  
Cerebral Ischemia ◽  
Neurological Deficit ◽  
Brain Function ◽  
Respiratory Function ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Succinic Dehydrogenase ◽  
Respiratory Enzymes ◽  
Neurochemical Mechanism ◽  
Neurological Deficit Score

We explored the neurochemical mechanism of electroacupuncture's (EA) protective effect on brain function in focal cerebral ischemia rats, using cerebral ischemia/reperfusion rats established by the middle cerebral artery occlusion (MCAO) method. Adult male Sprague–Dawley rats were randomly divided into four groups: Sham, Sham+EA, MCAO and MCAO+EA. The rats in Sham+EA and MCAO+EA were accepted EA treatment at ‘GV26’ and ‘GV20’ acupoints for 30 min. Electric stimulation was produced by a G-6805 generator and neurological deficit scores were recorded. Mitochondria respiratory function and the activities of respiratory enzymes were measured by a computer-aided Clark oxygen electrode system. Results showed that EA treatment might reduce the neurological deficit score, and significantly improve respiratory control ratio (RCR), the index of mitochondrial respiratory function, and increase the activities of succinic dehydrogenase, NADH dehydrogenase and cytochrome C oxidase in the MCAO rats. Results suggest that EA might markedly decrease the neurological deficit score, promote the activities of respiratory enzymes and reduce the generation of reactive oxygen species (ROS), resulting in improvement of respiratory chain function and anti-oxidative capability of brain tissues in the infarct penumbra zone. This be a mechanism of EA's anti-injury effect on brain function in MCAO rats.

Protective Effect of Astragaloside on Focal Cerebral Ischemia/Reperfusion Injury in Rats

2010 ◽  
Vol 38 (03) ◽  
pp. 517-527 ◽  
Author(s):  
Yan-Yan Yin ◽  
Wei-Ping Li ◽  
Hui-Ling Gong ◽  
Fen-Fang Zhu ◽  
Wei-Zu Li ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cerebral Ischemia ◽  
Water Content ◽  
Neurological Deficit ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Content Increase ◽  
Protective Effects ◽  
Neurological Deficit Score ◽  
Cerebral Ischemia Reperfusion

This study was to observe the neurological protective effects of astragalosides (AST) on focal cerebral ischemia-reperfusion (I/R) injury in rats and to explore its possible mechanism. Male SD rats received right middle cerebral artery occlusion for 120 min and AST (40 mg/kg) was orally administered. The rats were decapitated 1, 3, 7, and 14 days after reperfusion. The neurological deficit score, infarct volume and water content of brain were measured; the activity of superoxide dismutase (SOD), lactate dehydrogenase (LDH) and nitric oxide synthase (NOS), and the content of malondialdehyde (MDA), lactate (LD) and nitric oxide (NO) of brain tissue were detected too. The expression of inducible nitric synthase (iNOS), nerve growth factor (NGF) and tropomyosin receptor kinase A (TrkA) mRNA were measured by RT-PCR or real-time PCR. AST could significantly reduce the neurological deficit score; infract volume and water content, increase SOD and LDH activities, decrease NOS activity and MDA, LD and NO content. AST treatment could down-regulate expression of iNOS mRNA, while, NGF and TrkA mRNA were up-regulated. Our data suggest that AST have the protective effects on focal cerebral ischemia in rats at the different reperfusion time points, the mechanism may be related to the antioxidation, regulated the expressions of iNOS, NGF and TrkA mRNA.

Mechanism by which H-2g, a glucose analog of blood group H antigen, mediates angiogenesis

Blood ◽  
2005 ◽  
Vol 105 (6) ◽  
pp. 2343-2349 ◽  
Author(s):  
Kui Zhu ◽  
Mohammed Asif Amin ◽  
Yuanyuan Zha ◽  
Lisa A. Harlow ◽  
Alisa E. Koch
Keyword(s):  
Growth Factor ◽  
Critical Role ◽  
Aortic Ring ◽  
Nuclear Factor Κb ◽  
Janus Kinase ◽  
Intercellular Adhesion Molecule ◽  
Soluble Form ◽  
Intercellular Adhesion Molecule 1

AbstractThe 4A11 antigen is a unique cytokine-inducible antigen up-regulated on rheumatoid arthritis (RA) synovial endothelial cells (ECs) compared with normal ECs. Previously, we showed that in soluble form, this antigen, Lewisy-6/H-5-2 (Ley/H) or its glucose analog, 2-fucosyl lactose (H-2g), induced the expression of EC intercellular adhesion molecule-1 (ICAM-1) and leukocyte-endothelial adhesion through the Janus kinase 2 (JAK2)–signal transducer and activator of transcription 3 (STAT3) pathway. Currently, we show that H-2g induces release of EC angiogenic basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), an effect inhibited by decoy nuclear factor κB (NFκB) oligodeoxynucleotide (ODN). JAK2 and phosphoinositide-3 kinase (PI3K) are 2 upstream kinases of NFκB activated by H-2g, as confirmed by an inhibitor of kappa B kinase (IKKβ) assay. In vitro, H-2g induces vascular sprouting in the rat aortic ring model, whereas blockade of JAK2, PI3K, or NFκB inhibits sprouting. Likewise, in the in vivo mouse Matrigel plug angiogenesis assay, chemical inhibitors and antisense or decoy ODNs of JAK2, PI3K, or NFκB decrease angiogenesis, confirming the importance of these pathways in H-2g–induced EC signaling. The critical role of Ley/H involvement in angiogenesis and its signaling pathways may provide new targets for therapy of diseases characterized by pathologic neovascularization.

Cerulein upregulates ICAM-1 in pancreatic acinar cells, which mediates neutrophil adhesion to these cells

2000 ◽  
Vol 279 (4) ◽  
pp. G666-G676 ◽  
Author(s):  
Vjekoslav Zaninovic ◽  
Anna S. Gukovskaya ◽  
Ilya Gukovsky ◽  
Michelle Mouria ◽  
Stephen J. Pandol
Keyword(s):  
Acinar Cells ◽  
Neutrophil Infiltration ◽  
Nuclear Factor Κb ◽  
Pancreatic Acinar Cells ◽  
Intercellular Adhesion Molecule ◽  
Neutrophil Adhesion ◽  
Adhesion Assay ◽  
Intercellular Adhesion Molecule 1 ◽  
Basal Expression ◽  
Activation Of Transcription

Neutrophil infiltration into the pancreas is a key event in pancreatitis. Here we show that intercellular adhesion molecule-1 (ICAM-1), which regulates neutrophil adhesion, is present on rat pancreatic acinar cells, is upregulated by a hormone (cerulein) and mediates direct binding of neutrophils to acinar cells. ICAM-1 was upregulated in pancreas of rats with experimental pancreatitis induced by supramaximal doses of cerulein. Furthermore, cerulein time and dose dependently stimulated expression of ICAM-1 mRNA and protein in isolated pancreatic acinar cells. Inhibitory analysis showed that activation of transcription factor nuclear factor-κB (NF-κB) was involved in ICAM-1 upregulation by cerulein, but NF-κB did not mediate basal expression of ICAM-1 mRNA in acinar cells. With an adhesion assay, we found that neutrophils bind to isolated pancreatic acinar cells and that cerulein upregulates the extent of adhesion. Neutralizing ICAM-1 antibody blocked neutrophil binding to both control and cerulein-stimulated acinar cells, suggesting ICAM-1 involvement in this adhesion. Thus the acinar cell is capable of targeting neutrophils to its surface, a process that may be important for inflammatory and cell death responses in pancreatitis and other pancreatic disorders.

Effect of steroid on hyperoxia-induced ICAM-1 expression in pulmonary endothelial cells

2000 ◽  
Vol 278 (2) ◽  
pp. L245-L252 ◽  
Author(s):  
Yukio Suzuki ◽  
Kazumi Nishio ◽  
Kei Takeshita ◽  
Osamu Takeuchi ◽  
Kenji Watanabe ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Oxygen Toxicity ◽  
Immunoblot Analysis ◽  
Nuclear Factor Κb ◽  
Intercellular Adhesion Molecule ◽  
Dependent Manner ◽  
Activator Protein 1 ◽  
Intercellular Adhesion Molecule 1 ◽  
Mobility Shift

Intercellular adhesion molecule-1 (ICAM-1) of the vascular endothelium plays a key role in the development of pulmonary oxygen toxicity. We studied the effect of steroid on hyperoxia-induced ICAM-1 expression using cultured endothelial cells in vitro. Human pulmonary artery endothelial cells (HPAECs) were cultured to confluence, and then the monolayers were exposed to either control (21% O2-5% CO2) or hyperoxic (90% O2-5% CO2) conditions with and without a synthetic glucocorticoid, methylprednisolone (MP). MP reduced hyperoxia-induced ICAM-1 and ICAM-1 mRNA expression in a dose-dependent manner. Neutrophil adhesion to hyperoxia-exposed endothelial cells was also inhibited by MP treatment. In addition, MP attenuated hyperoxia-induced H2O2 production in HPAECs as assessed by flow cytometry. An electrophoretic mobility shift assay demonstrated that hyperoxia activated nuclear factor-κB (NF-κB) but not activator protein-1 (AP-1) and that MP attenuated hyperoxia-induced NF-κB activation dose dependently. With Western immunoblot analysis, IκB-α expression was decreased by hyperoxia and increased by MP treatment. These results suggest that MP downregulates hyperoxia-induced ICAM-1 expression by inhibiting NF-κB activation via increased IκB-α expression.

Monocyte Arrest and Transmigration on Inflamed Endothelium in Shear Flow Is Inhibited by Adenovirus-Mediated Gene Transfer of IκB-

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3685-3693 ◽  
Author(s):  
Kim S.C. Weber ◽  
Georg Draude ◽  
Wolfgang Erl ◽  
Rainer de Martin ◽  
Christian Weber
Keyword(s):  
Gene Transfer ◽  
Shear Flow ◽  
Adhesion Molecule ◽  
Recombinant Adenovirus ◽  
Surface Protein ◽  
Nuclear Factor Κb ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Monocyte Chemoattractant Protein 1 ◽  
Adenoviral Transfer

Abstract Mobilization of nuclear factor-κB (NF-κB) activates transcription of genes encoding endothelial adhesion molecules and chemokines that contribute to monocyte infiltration critical in atherogenesis. Inhibition of NF-κB has been achieved by pharmacological and genetic approaches; however, monocyte interactions with activated endothelium in shear flow following gene transfer of the NF-κB inhibitor IκB- have not been studied. We found that overexpression of IκB- in endothelial cells using a recombinant adenovirus prevented tumor necrosis factor- (TNF-)–induced degradation of IκB- and suppressed the upregulation of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin mRNA and surface protein expression and the upregulation of transcripts for the chemokines monocyte chemoattractant protein 1 (MCP-1) and growth-related activity- (GRO-) by TNF-. This was associated with a reduction in endothelial MCP-1 secretion and GRO- immobilization. Adhesion assays under physiological shear flow conditions showed that firm arrest, spreading, and transmigration of monocytes on TNF-–activated endothelium was markedly inhibited by IκB- overexpression. Inhibition with monoclonal antibodies and peptide antagonists inferred that this was due to reduced expression of Ig integrin ligand as well as of chemokines specifically involved in these events. In contrast, rolling of monocytes was increased by IκB- transfer and was partly mediated by P-selectin; however, it appeared to be unaffected by the inhibition of E-selectin induction. Thus, our data provide novel evidence that selective modulation of NF-κB by adenoviral transfer of IκB- impairs the expression of multiple endothelial gene products required for subsequent monocyte arrest and emigration in shear flow and thus for monocyte infiltration in atherosclerotic plaques.

scholarly journals Quercetin inhibits inducible ICAM-1 expression in human endothelial cells through the JNK pathway

1999 ◽  
Vol 277 (3) ◽  
pp. C403-C411 ◽  
Author(s):  
Hirotsugu Kobuchi ◽  
Sashwati Roy ◽  
Chandan K. Sen ◽  
Hao G. Nguyen ◽  
Lester Packer
Keyword(s):  
Adhesion Molecule ◽  
Inflammatory Responses ◽  
Surface Expression ◽  
Nuclear Factor Κb ◽  
Intercellular Adhesion Molecule ◽  
Mrna Levels ◽  
Intercellular Adhesion Molecule 1 ◽  
Jnk Pathway ◽  
Tnf Α ◽  
Dose Dependent

The cell adhesion molecule intercellular adhesion molecule-1 (ICAM-1) plays a pivotal role in inflammatory responses. Quercetin (3,3′,4′,5,7-pentahydroxyflavone), a naturally occurring dietary flavonol, has potent anti-inflammatory properties. The effect of quercetin on ICAM-1 expression induced by agonists phorbol 12-myristate 13-acetate (PMA) and tumor necrosis factor-α (TNF-α) in human endothelial cell line ECV304 (ECV) was investigated. Quercetin treatment downregulated both PMA- and TNF-α-induced surface expression, as well as the ICAM-1 mRNA levels, in ECV cells in a dose-dependent (10–50 μM) manner. Quercetin had no effect on PMA- or TNF-α-induced nuclear factor-κB (NF-κB) activation. However, under similar conditions a remarkable dose-dependent downregulation of activator protein-1 (AP-1) activation was observed. This decrease in AP-1 activation was observed to be associated with the inhibitory effects of quercetin on the c-Jun NH2-terminal kinase (JNK) pathway. These results suggest that quercetin downregulates both PMA- and TNF-α-induced ICAM-1 expression via inhibiting both AP-1 activation and the JNK pathway.

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