scholarly journals Total Saponins of Panax Notoginseng Exhibit Neuroprotection by The Activation of Akt/mTOR Pathway in Vitro and in Vivo

2020 ◽  
Author(s):  
Dong-Ping Wu ◽  
Yu-Wei Pan ◽  
Hua-Feng Liang ◽  
Gen-Yun Tang ◽  
Ming Chen ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cerebral Ischemia ◽  
Cortical Neurons ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Panax Notoginseng ◽  
Mtor Pathway ◽  
Dead Cell ◽  
Cerebral Ischemia Reperfusion ◽  
Underlying Mechanisms

Abstract Background: Panax notoginseng (Burkill) F.H.Chen is a traditional Chinese medicine. The present study reports the potential therapeutic effect of total saponins of Panax notoginseng (Burkill) F.H.Chen (TSPN) on ischemic stroke and investigates the underlying mechanisms. To reveal the neuroprotective effect of TSPN on cerebral ischemia-reperfusion injury and the underlying mechanisms.Methods: Oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons was used as a model of neuronal injury. The neuroprotective effect of TSPN was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and Live/Dead cell assay. The morphology of dendrites was detected by immunofluorescence. Rat middle cerebral artery occlusion (MCAO) was used as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological score, tail hang test, TTC staining, and Nissl staining. Western blot analysis, immunohistochemistry or immunofluorescence was used to measure the changes in Akt/mTOR signaling pathway.Results: MTT showed that TSPN had a rescue effect on cortical neurons after OGD/R-treated. Flow cytometry and Live/Dead cell assay indicated that TSPN decreased neuronal apoptosis, and immunofluorescence showed that TSPN restored dendrite morphology of the damaged neurons. Moreover, TSPN down-regulated the expressions of cleaved-Caspase-3 and LC3B-II/LC3B-I, whereas up-regulated the levels of phosphorylated (p)- Akt and p-mTOR. In MCAO model, TSPN rescued defective neurological behavior and reduced infarct volume. Moreover, the expressions of Beclin-1 and LC3B in cerebral ischemic penumbra were down-regulated after the treatment of TSPN, whereas p-mTOR level was up-regulated.Conclusion: TSPN show neuroprotective effects against OGD/R-induced cortical neuronal damage and exhibit potential therapeutic effects on cerebral ischemia in rat MCAO model. Up-regulation of mTOR pathway and inhibition of the autophagic pathway could be the mechanisms that underlie the action of TSPN.

scholarly journals Celastrol exerts a neuroprotective effect by directly binding to HMGB1 protein in cerebral ischemia–reperfusion

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Dan-Dan Liu ◽  
Piao Luo ◽  
Liwei Gu ◽  
Qian Zhang ◽  
Peng Gao ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Cortical Neurons ◽  
Chemical Constituents ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Parent Compound ◽  
High Mobility Group Protein ◽  
Neuroprotective Effects ◽  
Adult Rats ◽  
Cerebral Ischemia Reperfusion

Abstract Background Celastrol (cel) was one of the earliest isolated and identified chemical constituents of Tripterygium wilfordii Hook. f. Based on a cel probe (cel-p) that maintained the bioactivity of the parent compound, the targets of cel in cerebral ischemia–reperfusion (I/R) injury were comprehensively analyzed by a quantitative chemical proteomics method. Methods We constructed an oxygen–glucose deprivation (OGD) model in primary rat cortical neurons and a middle cerebral artery occlusion (MCAO) model in adult rats to detect the direct binding targets of cel in cerebral I/R. By combining various experimental methods, including tandem mass tag (TMT) labeling, mass spectrometry, and cellular thermal shift assay (CETSA), we revealed the targets to which cel directly bound to exert neuroprotective effects. Results We found that cel inhibited the proinflammatory activity of high mobility group protein 1 (HMGB1) by directly binding to it and then blocking the binding of HMGB1 to its inflammatory receptors in the microenvironment of ischemia and hypoxia. In addition, cel rescued neurons from OGD injury in vitro and decreased cerebral infarction in vivo by targeting HSP70 and NF-κB p65. Conclusion Cel exhibited neuroprotective and anti-inflammatory effects by targeting HSP70 and NF-κB p65 and directly binding to HMGB1 in cerebral I/R injury.

Syringin protects against cerebral ischemia/reperfusion injury via inhibiting neuroinflammation and TLR4 signaling

Perfusion ◽  
2021 ◽  
pp. 026765912110070
Author(s):  
Yan Liu ◽  
Xuyao Zhu ◽  
Xiuxia Tong ◽  
Ziqiang Tan
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Learning And Memory ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Cerebral Damage ◽  
Memory Ability ◽  
Cerebral Ischemia Reperfusion ◽  
Cerebral Ischemia Reperfusion Injury

Introduction: Cerebral ischemia/reperfusion injury (CI/R) is associated with high mortality and remains a large challenge in the clinic. Syringin is a bioactive compound with anti-inflammation, antioxidant, as well as neuroprotective effects. Nevertheless, whether syringin could protect against CI/R injury and its potential mechanism was still unclear. Methods: Rats were randomly divided into five groups: sham group, syringin group, CI/R group, CI/R + syringin group, and CI/R + syringin + LPS (TLR4 agonist) group. The CI/R injury rat model was established by the middle cerebral artery occlusion (MCAO). The learning and memory ability of rats was estimated by the Morris water maze test. Modified neurological severity score test (mNSS) and infarct volume were detected to assess the neuroprotective effect of syringin. ELISA and RT-qPCR were used to analyze the concentration of proinflammation cytokines and the expression of TLR4. Results: CI/R injury induced increased mNSS scores and decreased learning and memory ability of rats. Syringin could significantly protect against CI/R injury as it decreased the cerebral damage and improved the cognitive ability of CI/R rats. Moreover, syringin also reduced neuroinflammation of CI/R injury rats. Additionally, TLR4 was significantly upregulated in CI/R injury rats, which was suppressed by syringin. The activation of TLR4 reversed the neuroprotective effect of syringin in CI/R rats. Conclusion: Syringin decreased the inflammation reaction and cerebral damage in CI/R injury rats. The neuroprotective effect of syringin may be correlated with the inhibition of TLR4.

Neuroprotective Effects of Alisol A 24-acetate on Cerebral Ischemia-reperfusion Injury by Regulating PI3K/AKT Pathway

2021 ◽  
Author(s):  
Taotao Lu ◽  
Huihong Li ◽  
Yangjie Zhou ◽  
Wei Wei ◽  
Linlin Ding ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Brain Regions ◽  
Global Cerebral Ischemia ◽  
Akt Pathway ◽  
Object Recognition Test ◽  
Neuroprotective Effects ◽  
Cerebral Ischemia Reperfusion

Abstract BackgroundNeuroinflammation and apoptosis are involved in the pathogenesis of ischemic stroke. Alisol A 24-acetate (24A) has a strong inhibitory effect on inflammation and cell apoptosis. The neuroprotective effect of 24A in the global cerebral ischemia/ reperfusion (GCI/R) is still unclear. Methods GCI/R mice was used to investigated the neuroprotective effect of 24A. Modified neurological deficit scores, Morris Water Maze and object recognition test were used to evaluate behaviors. The metabolism in brain regions was detected by MRS. The changes of microglia, astrocytes and neurons was detected. The inflammation and apoptosis were measured.Results The results showed that 24A improved behavioral dysfunction and brain metabolism, alleviate neuroinflammation and apoptosis, inhibited microglia and astrocytes activation, which is associated with the activation of PI3K/AKT pathway. ConclusionsTaken together, our study demonstrated that 24A could alleviate GCI/R injury through anti-neuroinflammation and anti-apoptosis via regulating the PI3K/AKT pathway.

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