scholarly journals NLRC5 alleviated OGD/R-induced PC12-cell injury by inhibiting activation of the TLR4/MyD88/NF-κB pathway

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094045
Author(s):  
Zhen Zhang ◽  
Yuhan Sun ◽  
Xin Chen
Keyword(s):  
Cerebral Ischemia ◽  
Oxidative Damage ◽  
Pc12 Cells ◽  
Pc12 Cell ◽  
Cell Injury ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Apoptosis Rate

Objective To assess the role of NOD-like receptor C5 (NLRC5; a major NLRC family protein that regulates immunity, inflammation and tissue fibrosis), in cerebral ischemia-reperfusion injury, characterized by inflammation and oxidative damage. Methods Blood NLRC5 levels were assessed in neonates with cerebral ischemia and in healthy controls. A stable PC12 cell line was established that overexpressed or knocked down NLRC5. Inflammatory responses, apoptosis rate and oxidative damage in PC12 cells under oxygen-glucose deprivation/reperfusion (OGD/R) conditions were evaluated using enzyme-linked immunosorbent assay (ELISA), terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) and reactive oxygen species (ROS) assay. Results Blood NLRC5 levels were suppressed in neonates with cerebral ischemia. ELISAs showed that NLRC5 suppressed levels of tumour necrosis factor-α, interleukin (IL)-6, IL-1β, ROS and superoxide dismutase in OGD/R-treated PC12 cells. Furthermore, NLRC5 overexpression was associated with reduced apoptosis rate in PC12 cells treated by OGD/R. Overexpression of NLRC5 also inhibited levels of toll-like receptor (TLR)4, myeloid differentiation primary response protein MyD88 (MyD88) and phosphorylated nuclear factor kappa B-transcription factor p65 (NF-κB p-p65) in PC12 cells, and decreased nuclear levels of NF-κB p-p65. Conclusion NLRC5 alleviated inflammatory responses, oxidative damage and apoptosis in PC12 cells under OGD/R conditions by suppressing activation of the TLR4/MyD88/NF-κB pathway.

(Z)-7,4′-Dimethoxy-6-hydroxy-aurone- 4-O-β-glucopyranoside alleviates cerebral ischemia-reperfusion injury in rats associating with the regulation of JAK1/STAT1 signaling pathway

2020 ◽  
Vol 39 (11) ◽  
pp. 1507-1517
Author(s):  
R Du ◽  
X Zhou ◽  
D Yang ◽  
H Zhou ◽  
F Lin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Protein Expression ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Janus Kinase ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cerebral Ischemia Reperfusion ◽  
Brain Tissues

Inflammatory responses have been demonstrated to contribute to the neuronal death following cerebral ischemia. This study was to investigate the repairing effects and potential mechanisms of (Z)-7,4′-dimethoxy-6-hydroxy-aurone-4-O-β-glucopyranoside (DHAG), a compound with neuroprotective effects, on cerebral ischemia-reperfusion (I/R) injury in rats. Cerebral I/R model was established with middle cerebral artery occlusion method in Sprague Dawley rats and then rats were treated with DHAG (1 and 2 mg/kg) for 7 days. The volume of cerebral infarction was detected by triphenyltetrazolium chloride staining. The apoptosis in ischemic brain tissues was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Oxidative stress markers and inflammatory factors were detected by enzyme-linked immunosorbent assay. Protein expression was detected by Western blot. DHAG treatment significantly alleviated the cerebral I/R injury and decreased apoptosis in brain tissues. Moreover, DHAG treatment significantly inhibited oxidative stress and reduced inflammatory responses, associating with decreasing the protein expression of phosphorylated Janus kinase 1/phosphorylated signal transducer and transcriptional activator 1. These results demonstrated neuroprotective properties of DHAG and highlighted it as a potential therapeutic agent against injury of cerebral IR.

scholarly journals Protective Action of Betulinic Acid on Cerebral Ischemia/Reperfusion Injury through Inflammation and Energy Metabolic Homeostasis

2020 ◽  
Vol 10 (7) ◽  
pp. 2578
Author(s):  
Wenjiao Jiang ◽  
Kun Hao
Keyword(s):  
Cerebral Ischemia ◽  
Betulinic Acid ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Action ◽  
Enzyme Linked Immunosorbent Assay ◽  
Protective Effects ◽  
Cerebral Ischemia Reperfusion

This work evaluated the protective effects of betulinic acid (BA) in vitro cerebral ischemia/reperfusion and provides clues about its pharmacological mechanism. A rat model of middle cerebral artery occlusion (MCAO) was established to investigate the effects of BA on cerebral ischemia. SHSY5Y cell injury was induced by oxygen–glucose deprivation and recovery (OGD/R) to further verify the action of BA in vitro. Our data show a significant improvement in infarct size, neurological score, and cerebral edema after BA treatment. Enzyme linked immunosorbent assay (ELISA) data show that BA inhibited interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in vivo and in vitro. Protein expression results show that BA down-regulated hypoxia-inducible factor-1α (HIF-1α), up-regulated adenosine monophosphate activated protein kinase (AMPK), peroxisome proliferative activated receptor (PPAR)-α, and PPAR-γ coactivator-1α (PGC-1α), and blocked phosphorylation of IκBα and nuclear factor kappa Bp65 (NF-κB-p65) in the brains of MCAO rats and OGD/R-stimulated SHSY5Y cells. The results reveal the potent effects of BA on cerebral ischemia, suggesting that HIF-1α might be a crucial therapeutic target to regulate energy metabolism and inflammation.

scholarly journals The Antioxidant, Anti-Inflammatory and Anti-Apoptotic Activities of the Bauhinia Championii Flavone are Connected with Protection Against Myocardial Ischemia/Reperfusion Injury

2016 ◽  
Vol 38 (4) ◽  
pp. 1365-1375 ◽  
Author(s):  
Jie Jian ◽  
Feifei Xuan ◽  
Feizhang Qin ◽  
Renbin Huang
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion

Background/Aims: Previous studies have demonstrated that Bauhinia championii flavone (BCF) exhibits anti-oxidative, anti-hypoxic and anti-stress properties. This study was designed to investigate whether BCF has a cardioprotective effect against myocardial ischemia/reperfusion (I/R) injuries in rats and to shed light on its possible mechanism. Methods: The model of I/R was established by ligating the left anterior descending coronary artery for 30 min, then reperfusing for 180 min. Hemodynamic changes were continuously monitored. The content of malondialdehyde (MDA) as well as the lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed. The release of interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis of cardiomyocytes was determined by caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of TLR4, NF-κBp65, Bcl-2 and Bax were detected by western blotting. Results: Pretreatment with BCF significantly reduced the serum levels of LDH, MDA and IL-6, but increased the activities of SOD and GSH-Px. It also attenuated myocardial infarct size, reduced the apoptosis rate and preserved cardiac function. Furthermore, BCF inhibited caspase-3 activity and the expression of TLR4, phosphorylated NF-κBp65 and Bax, but enhanced the expression of Bcl-2. Conclusion: These results provide substantial evidence that BCF exerts a protective effect on myocardial I/R injury, which may be attributed to attenuating lipid peroxidation, the inflammatory response and apoptosis.

scholarly journals Safflower Yellow B Protects Brain against Cerebral Ischemia Reperfusion Injury through AMPK/NF-kB Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Shibin Du ◽  
Youliang Deng ◽  
Hongjie Yuan ◽  
Yanyan Sun
Keyword(s):  
Brain Injury ◽  
Cerebral Ischemia ◽  
Pc12 Cells ◽  
Inflammatory Cytokines ◽  
Nuclear Translocation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Secondary Damage

Inflammation had showed its important role in the pathogenesis of cerebral ischemia and secondary damage. Safflower yellow B (SYB) had neuroprotective effects against oxidative stress-induced brain injuries, but the mechanisms were still largely unknown to us. In this study, we tried to investigate the anti-inflammation effects of SYB and the possible roles of AMPK/NF-κB signaling pathway on these protective effects. In vivo, brain ischemia/reperfusion (I/R) was induced by transient middle cerebral artery occlusion for 2 h and reperfusion for 20 h. Neurofunctional evaluation, infarction area, and brain water contents were measured. Brain injury markers and inflammatory cytokines levels were measured by ELISA kits. In vitro, cell viability, apoptosis, and LDH leakage were measured after I/R in PC12 cells. The expression and phosphorylation levels of AMPK, NF-κB p65, and P-IκB-α in cytoplasm and nuclear were measured by Western blotting. SiRNA experiment was performed to certify the role of AMPK. The results showed SYB reduced infarct size, improved neurological outcomes, and inhibited brain injury after I/R. In vitro test, SYB treatment alleviated PC12 cells injury and apoptosis and inhibited the inflammatory cytokines (IL-1, IL-6, TNF-α, and COX-2) in a dose-dependent manner. SYB treatment induced AMPK phosphorylation and inhibited NF-κB p65 nuclear translocation both in brain and in PC12 cells. Further studies also showed that the inhibition of NF-κB activity of SYB was through AMPK. In conclusion, SYB protected brain I/R injury through reducing expression of inflammatory cytokines and this effect might be partly due to the inhibition of NF-κB mediated by AMPK.

scholarly journals RiPerC Attenuates Cerebral Ischemia Injury through Regulation of miR-98/PIK3IP1/PI3K/AKT Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Dengwen Zhang ◽  
Li Mei ◽  
Ruichun Long ◽  
Can Cui ◽  
Yi Sun ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Regulatory Mechanism ◽  
Ischemia Reperfusion ◽  
Quantitative Polymerase Chain Reaction ◽  
Akt Signaling ◽  
Enzyme Linked Immunosorbent Assay ◽  
Akt Signaling Pathway ◽  
Remote Ischemic Perconditioning ◽  
Cerebral Ischemic

Background. Cerebral ischemic stroke is a refractory disease which seriously endangers human health. Remote ischemic perconditioning (RiPerC) by which the sublethal ischemic stimulus is administered during the ischemic event is beneficial after an acute stroke. However, the regulatory mechanism of RiPerC that relieves cerebral ischemic injury is still not completely clear. Methods. In the present study, we investigated the regulatory mechanism of RiPerC in a rat model of ischemia induced by the middle cerebral artery occlusion (MCAO). Forty-eight adult male Sprague-Dawley (SD) rats were injected intracerebroventricularly with miR-98 agomir, miR-98 antagomir, or their negative controls (agomir-NC, antagomir-NC) 2 h before MCAO or MCAO+RiPerC followed by animal behavior tests and infraction volume measurement at 24 h after MCAO. The expression of miR-98, PIK3IP1, and tight junction proteins in rat hippocampus and cerebral cortex tissues was detected by quantitative polymerase chain reaction (qPCR) and Western blot (WB). Enzyme-linked immunosorbent assay (ELISA) was used to assess the IL-1β, IL-6, and TNF-α levels in the rat serum. Results. The results showed that in MCAO group, the expression of PIK3IP1 was upregulated, but decreased after RiPerC treatment. Then, we found that PIK3IP1 was a potential target of miR-98. Treatment with miR-98 agomir decreased the infraction volume, reduced brain edema, and improved neurological functions compared to control rats. But treating with miR-98 antagomir in RiPerC group, the protective effect on cerebral ischemia injury was canceled. Conclusion. Our finding indicated that RiPerC inhibited the MCAO-induced expression of PIK3IP1 through upregulated miR-98, thereby reducing the apoptosis induced by PIK3IP1 through the PI3K/AKT signaling pathway, thus reducing the cerebral ischemia-reperfusion injury.

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