scholarly journals Benzoinum exerts NVU protective effect by inhibiting cell apoptosis in cerebral ischemia rats

2020 ◽  
Author(s):  
Qian Xie ◽  
Rong Ma ◽  
Xiaoqing Guo ◽  
Hai Chen ◽  
Jian Wang
Keyword(s):  
Ischemic Stroke ◽  
Protective Effect ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Cerebrovascular Diseases ◽  
Neuroprotective Activity ◽  
Stroke Therapy ◽  
Function Score ◽  
Cerebral Ischemic

Abstract Background Benzoinum (Styraceae) is a traditional Chinese medicine known to treat stroke and other cardio-cerebrovascular diseases for thousands of years. Benzoinum also proved to have diverse pharmacological activity, but the neuroprotection mechanism about apoptosis in ischemic stroke were not found. This study is to investigate the NVU protective effect and mechanisms of benzoinum on cerebral ischemic rats. Methods The neuroprotective activity of benzoinum against MCAO induced cerebral ischemic injury. Neurological scores, TTC staining, HE staining were conducted to evaluate neurological damage. Infarction rate and DCI were calculated. The ultrastructure of neuron and BBB was observed by TEM. Immunohistochemistry and RT-PCR were used to detect the Bax, Bcl-2, Caspase 3 expression. In addition, Claudin 5 also was detected by immunohistochemistry. Results The findings shown that benzoinum could significantly improve the neurological function score, reduce the cerebral infarction rate and DCI. Furthermore, benzoinum alleviated pathomorphological change and apoptosis in brain tissue of MCAO rats. The results of TEM and claudin 5 expression of immunohistochemistry showed that benzoinum could play a neuroprotective effect in NVU. Besides, benzoinum enhanced Bcl2, reduced Bax and Bax/Bcl-2, Caspase 3, suggesting benzoinum provided neuroprotective effect by inhibited cell apoptosis. Conclusion Benzoinum could play a neuroprotective role and regulate apoptosis to repair and stabilize NVU. Our present findings provide a promising medicine for treatment of ischemic stroke therapy.

scholarly journals The Neuroprotective Effect of l-Borneolum on Cerebral Ischemic Stroke by Regulating Dll4/Notch1 Pathway

2021 ◽  
Author(s):  
Taiwei Dong ◽  
Nian Chen ◽  
Rong Ma ◽  
Qian Xie ◽  
Xiaoqing Guo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Artery Occlusion ◽  
Neurological Function ◽  
Immunohistochemical Method ◽  
Triphenyltetrazolium Chloride ◽  
Severity Scores ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

Abstract Aiml-Borneolum is a monoterpene compound witch deserved from Blumea balsamifera (L.) DC, this study aimed to investigate the potential mechanism of l-borneolum on cerebral ischemic stroke (CIS) rats and provide evidence for the development of l-borneolum in CIS.MethodsPermanent middle cerebral artery occlusion (pMCAO) model rats were applied to this study. Neurological function was assessed by modified neurological severity scores (mNSS) and Longa neurological function scoring methods. The pathological changes of cerebral tissue were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin (HE) staining. Ultrastructure of blood brain barrier (BBB) was observed by transmission electron microscopy. Additionally, the expression of Notch1, Dll4, Hey1, Hes1, Hes5, VEGFA and p65 in the cortex were determined by Western blotting (WB) while expression of caspase 3 were determined by immunohistochemical method (IHC). Resultsl-Borneolum improved neurological function in a dose-dependently. l-Borneolum significantly alleviated brainstem edema and inflammation, as well as improved the ultrastructure of capillary and BBB in cortex. Moreover, 0.2 g/kg l-borneolum substantially decreased the protein expressions of Dll4, Notch1, Hes1, Hes5, and VEGFA in the cortex while decreased the level of Caspase-3 in the cortex of rats. Conclusionsl-Borneolum could repair neurological function by regulating Dll4/Notch1 signaling pathway.

scholarly journals Artemisinin attenuated oxidative stress and apoptosis by inhibiting autophagy in MPP+-treated SH-SY5Y cells

2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Junqiang Yan ◽  
Hongxia Ma ◽  
Xiaoyi Lai ◽  
Jiannan Wu ◽  
Anran Liu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Membrane Potential ◽  
Protein Expression ◽  
Mitochondrial Membrane Potential ◽  
Western Blotting ◽  
Cell Apoptosis ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Neuroprotective Effects

Abstract Background Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. The oxidative stress is an important component of the pathogenesis of PD. Artemisinin (ART) has antioxidant and neuroprotective effects. The purpose of this study is to explore the neuroprotective effect of ART on 1-methyl-4-phenyliodine iodide (MPP +)-treated SH-SY5Y cells and underlying mechanism. Methods We used MPP+-treated SH-SY5Y cells to study the neuroprotective effect of ART. Cell viability was measured by MTT assay after incubating the cells with MPP+ and/or ART for 24 h. DCFH-DA was used to detect the level of intracellular reactive oxygen species (ROS), and WST-8 was used to detect the level of superoxide dismutase (SOD). The level of intracellular reduced glutathione (GSH) was detected with 5,5΄-dithiobis-(2-nitrobenzoic acid), and the level of malondialdehyde (MDA) was assessed based on the reaction of MDA and thiobarbituric acid. A mitochondrial membrane potential detection kit (JC-1) was used to detect changes in the mitochondrial membrane potential (MMP), and an Annexin V-FITC cell apoptosis kit was used to detect cell apoptosis. The expression levels of caspase-3, cleaved caspase-3 and the autophagy-related proteins LC3, beclin-1, and p62 were detected by Western blotting. In addition, to verify the change in autophagy, we used immunofluorescence to detect the expression of LC3 and p62. Results No significant cytotoxicity was observed at ART concentrations up to 40 μM. ART could significantly increase the viability of SH-SY5Y cells treated with MPP+ and reduce oxidative stress damage and apoptosis. In addition, the Western blotting and immunofluorescence results showed that MPP+ treatment could increase the protein expression of beclin1 and LC3II/LC3I and decrease the protein expression of p62, indicating that MPP+ treatment could induce autophagy. Simultaneous treatment with ART and MPP+ could decrease the protein expression of beclin1 and LC3II/LC3I and increase the protein expression of p62, indicating that ART could decrease the level of autophagy induced by MPP+. Conclusion Our results indicate that ART has a protective effect on MPP+-treated SH-SY5Y cells by the antioxidant, antiapoptotic activities and inhibition of autophagy. Our findings may provide new hope for the prevention and treatment of PD.

Abstract WP62: Enhanced Neuroprotection of Normobaric Oxygenation with Ethanol Conferred by Apoptosis Reduction in Acute Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Sweena Parmar ◽  
Xiaokun Geng ◽  
Changya Peng ◽  
Murali Guthikonda ◽  
Yuchuan Ding
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Neuroprotective Effect ◽  
Apoptotic Cell Death ◽  
Ethanol Administration ◽  
Sprague Dawley ◽  
Apoptotic Proteins

Objectives: Normobaric oxygenation (NBO) has been shown to provide neuroprotection in vivo and in vitro . Yet, a recent Phase 2 clinical trial investigating NBO therapy in acute ischemic stroke was terminated due to questionable therapeutic benefit. NBO therapy alone may be insufficient to produce improved outcomes. In our recent study, we demonstrated a strong neuroprotective effect of ethanol at a dose of 1.5 g/kg (equivalent to the human legal driving limit). In this study, we sought to identify whether low-dose ethanol administration enhances the neuroprotection offered by NBO and whether combined administration of NBO with ethanol is associated with reduced apoptosis. Methods: Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. Ischemic animals received either an intraperitoneal injection of 1.0 g/kg ethanol, 2 h of 100% NBO, or both ethanol and NBO. The Cell Death Detection ELISA Assay (Roche) was performed to determine apoptotic cell death at 24 h after reperfusion. Levels of pro-apoptotic (Caspase-3, Bcl-2-associated X-BAX, and Apoptosis-Inducing Factor-AIF) and anti-apoptotic proteins (Bcl-2 and Bcl-xL) were determined by Western blot analysis at 3 and 24 h after reperfusion. Results: As expected, untreated ischemic rats had the highest apoptotic cell death. Combined NBO/ethanol therapy decreased cell death by 48%, as compared to 29% with ethanol and 22% with NBO. Similarly, combined NBO/ethanol therapy promoted the greatest expression of anti-apoptotic factors and the lowest expression of pro-apoptotic proteins at 3 h after reperfusion. This effect was maintained at 24 h and even more pronounced for AIF and Caspase-3. Conclusions: Given singularly, NBO and ethanol improved the degree of cell death, decreased the expression of pro-apoptotic proteins, and increased the expression of anti-apoptotic proteins. Yet, when administered together, their effects largely compounded. These results suggest a synergistic neuroprotection offered by NBO with ethanol, which may be attributed at least in part to their shared role in modulating neuronal apoptosis.

Memantine attenuates cell apoptosis by suppressing the calpain-caspase-3 pathway in an experimental model of ischemic stroke

2017 ◽  
Vol 351 (2) ◽  
pp. 163-172 ◽  
Author(s):  
Bin Chen ◽  
Guoxiang Wang ◽  
Weiwei Li ◽  
Weilin Liu ◽  
Ruhui Lin ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Experimental Model ◽  
Cell Apoptosis ◽  
Caspase 3

scholarly journals Calreticulin Binds to Fas Ligand and Inhibits Neuronal Cell Apoptosis Induced by Ischemia-Reperfusion Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Beilei Chen ◽  
Zhengzheng Wu ◽  
Jun Xu ◽  
Yun Xu
Keyword(s):  
Reperfusion Injury ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Fas Ligand ◽  
Ischemia Reperfusion Injury ◽  
Early Stage ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Neuronal Cell ◽  
Caspase 8

Background. Calreticulin (CRT) can bind to Fas ligand (FasL) and inhibit Fas/FasL-mediated apoptosis of Jurkat T cells. However, its effect on neuronal cell apoptosis has not been investigated.Purpose. We aimed to evaluate the neuroprotective effect of CRT following ischemia-reperfusion injury (IRI).Methods. Mice underwent middle cerebral artery occlusion (MCAO) and SH-SY5Y cells subjected to oxygen glucose deprivation (OGD) were used as models for IRI. The CRT protein level was detected by Western blotting, and mRNA expression of CRT, caspase-3, and caspase-8 was measured by real-time PCR. Immunofluorescence was used to assess the localization of CRT and FasL. The interaction of CRT with FasL was verified by coimmunoprecipitation. SH-SY5Y cell viability was determined by MTT assay, and cell apoptosis was assessed by flow cytometry. The measurement of caspase-8 and caspase-3 activity was carried out using caspase activity assay kits.Results. After IRI, CRT was upregulated on the neuron surface and bound to FasL, leading to increased viability of OGD-exposed SH-SY5Y cells and decreased activity of caspase-8 and caspase-3.Conclusions. This study for the first time revealed that increased CRT inhibited Fas/FasL-mediated neuronal cell apoptosis during the early stage of ischemic stroke, suggesting it to be a potential protector activated soon after IRI.

scholarly journals LncRNA WT1-AS Attenuates hypoxia/ischemia Induced Neuronal Injury in Cerebral Ischemic Stroke via miR-186-5p/XIAP Axis

2021 ◽  
Author(s):  
Jianquan You ◽  
Fei Qian ◽  
Yu Huang ◽  
Yingxuan Guo ◽  
Yaqian Lv ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cell Viability ◽  
Cell Apoptosis ◽  
Neuronal Damage ◽  
Luciferase Reporter ◽  
Occurrence Rate ◽  
Pcr Analysis ◽  
Gene Assay ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic

Abstract BackgroundCerebral ischemic stroke was a nervous system disease with high occurrence rate and mortality rate. This study aimed to investigate the role and mechanism of lncRNA WT1-AS in cerebral ischemic stroke. Materials and methodsStarbase and dual luciferase reporter gene assay were used to analyze the target relationship between lncRNA WT1-AS and miR-186-5p. qRT-PCR analysis was used to detect lncRNA WT1-AS and miR-186-5p expression. OGD-induced SH-SY5Y cells injury model was conducted, and cell viability and cell apoptosis were determined by MTT and flow cytometer assay. Caspase3 ability was determined using Caspase3 activity detection kit. ResultsmiR-186-5p was a target of lncRNA-WT1-AS. lncRNA WT1-AS was down-regulated and miR-186-5p was up-regulated in blood samples of patients with ischemic stroke and in OGD-induced SH-SY5Y cells. We found that WT1-AS-plasmid promoted OGD-induced cell viability, reduced cell apoptosis and decreased caspase3 ability, and these changes were reversed by miR-186-5p mimic. Subsequently, our results proved that XIAP was a target of miR-186-5p. Similarly, miR-186-5p inhibitor reduced OGD-induced neuronal damage by up-regulating XIAP expression. ConclusionlncRNA-WT1-AS/miR-186-5p/XIAP might be a new target for cerebral ischemic stroke treatment.

scholarly journals Based on Dll4/Notch1 Signaling Pathway to Elucidate the Therapeutic Effect and Mechanism of L-borneolum on Cerebral Ischemic Stroke Rats

2021 ◽  
Author(s):  
Taiwei Dong ◽  
Nian Chen ◽  
Rong Ma ◽  
Qian Xie ◽  
Xiaoqing Guo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Caspase 3 ◽  
Neurological Function ◽  
Immunohistochemical Method ◽  
Research Progress ◽  
Notch1 Signaling ◽  
Cerebral Ischemic Stroke ◽  
Cerebral Ischemic ◽  
Notch1 Signaling Pathway

Abstract Background: The current research progress suggests that a single therapy may not be ideal means for complex cerebral ischemic stoke (CIS). l-Borneolum is the crystallization of fresh leaves of Blumea balsamifera (L.) DC, we have found that l-borneolum plays a best anti-cerebral ischemic effect than d-borneolum or synthetic borneolum. However, the mechanism is needed to be explored in depth. Therefore, based on comprehensive approach that combines molecular docking technology and molecular biology, this stiudy aimed to investigate the potential mechanism of l-borneolum on CIS rats and provide scientific evidence for the treatment of l-borneolum in CIS.Methods: Cerebral ischemic stroke (CIS) rats with permanent middle cerebral artery occlusion (pMCAO) were applied to this study. The modified neurological severity scores (mNSS) and Longa neurological function scoring methods were used to assess the neurobehavioral scores. 2,3,5-Triphenyltetrazolium chloride (TTC) staining and hematoxylin-eosin (HE) staining were used to evaluate pathological changes of cerebral tissue. Ultrastructure of cortical capillary and blood-brain barrier (BBB) in rats were observed by transmission electron microscopy. In addition, the protein expression of Notch1, Dll4, Hey1, Hes1, Hes5, VEGFA and p65 in the cortex of rats were determined by Western blotting (WB). The protein contents of Caspase 3 in the cortex of rats were determined by immunohistochemical method (IHC). Results: l-Borneolum could prolong the resuscitation time, reduce the abnormal increased rectal temperature, improve neurological function in a dose-dependently. Additionally, l-borneolum could significantly alleviate brainstem edema and inflammation, as well as improve the ultrastructure of capillary and BBB in cortex. Moreover, 0.2 g/kg l-borneolum could substantially decrease the protein expressions of Dll4, Notch1, Hes1, Hes5, and VEGFA in the cortex while it decreased the level of Caspase-3 in the cortex of rats. Conclusions: l-Borneolum could repair neurological function by regulating Dll4/Notch1 signaling pathway, l-borneolum might be a good complementary agent for CIS.

scholarly journals Neuroprotective Activity of Water Soluble Extract fromChorispora bungeanaagainst Focal Cerebral Ischemic/Reperfusion Injury in Mice

2014 ◽  
Vol 2014 ◽  
pp. 1-9
Author(s):  
Ya-Xuan Sun ◽  
Ting Liu ◽  
Xue-Ling Dai ◽  
Ya-Bo Li ◽  
Yu-Yao Li ◽  
...  
Keyword(s):  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Water Extract ◽  
Water Soluble ◽  
Neuroprotective Activity ◽  
Control Group ◽  
Chorispora Bungeana ◽  
Model Control ◽  
Water Soluble Extract ◽  
Cerebral Ischemic

The purpose of the present study was to clarify whether the water extract ofChorispora bungeanawas an antioxidant agent against cerebral ischemia/reperfusion (I/R). Our results showed that water extract ofChorispora bungeanatreatment significantly reduced neurological deficit scores, infarct size, MDA and carbonyl contents, and GSH/GSSG ratio compared with the model control group. After being treated byChorispora bungeana, SOD, CAT, and GSH-Px activities remarkably increased.Chorispora bungeanatreatment also improved 8-OHdG expression and cell apoptosis. Our findings indicated that the water extract ofChorispora bungeanapossesses neuroprotective effect which is most likely achieved by antioxidant and antiapoptotic activities.

Tanshinone IIA Attenuates H2O2-Induced Injury in Human Umbilical Vein Endothelial Cells

2012 ◽  
Vol 40 (06) ◽  
pp. 1307-1319 ◽  
Author(s):  
Paul Chan ◽  
Yen-Cheng Chen ◽  
Li-Jen Lin ◽  
Tzu-Hurng Cheng ◽  
Kazunori Anzai ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Protective Effect ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Umbilical Vein ◽  
Tanshinone Iia ◽  
Cardiovascular Disorders ◽  
P53 Expression ◽  
Umbilical Vein Endothelial Cells

The injury of endothelial cell is the critical event of vascular disease. In endothelial cell, oxidative stress is regarded as critical to pathogenic factors in endothelial cell injury and apoptosis. Tanshinone IIA is the main effective component of Salvia miltiorrhiza known as "Danshen" in traditional Chinese medicine for treating cardiovascular disorders, but the mechanism by which it exerts the protective effect is not well established. The present study was designed to test the hypothesis that tanshinone IIA can inhibit hydrogen peroxide ( H2O2 )-induced injury and unravel its intracellular mechanism in human umbilical vein endothelial cells (HUVECs). In this study, HUVECs were treated with tanshinone IIA in the presence/absence of H2O2 . The protective effects of tanshinone IIA against H2O2 were evaluated. Our results show that HUVECs incubated with 200 μM H2O2 had significantly decreased the viability of endothelial cells, which was accompanied with apparent cell apoptosis, the activation of caspase-3 and the upregulation of p53 expression, which was known to play a key role in H2O2 -induced cell apoptosis. However, pretreatment with tanshinone IIA (3–10 μM) resulted in a significant resistance to H2O2 -induced apoptosis. In addition, pretreatment with tanshinone IIA decreased the activity of caspase-3 and p53 expression. Tanshinone IIA also induced activating transcription factor (ATF) 3 expression; while knockdown of ATF-3 with ATF-3 siRNAsignificantly reduced tanshinone IIA's protective effect. In conclusion, the present study shows that tanshinone IIA can protect endothelial cells against oxidative injury induced by H2O2 , suggesting that this compound may constitute a promising intervention against cardiovascular disorders and ATF-3 may play an important role in this process.

scholarly journals Neuroprotective Effects of Purple Sweet Potato Balinese Cultivar in Wistar Rats With Ischemic Stroke

2018 ◽  
Vol 6 (11) ◽  
pp. 1959-1964 ◽  
Author(s):  
I Made Oka Adnyana ◽  
AA Raka Sudewi ◽  
DPG Purwa Samatra ◽  
DN Suprapta
Keyword(s):  
Ischemic Stroke ◽  
Cytochrome C ◽  
Sweet Potato ◽  
Ipomoea Batatas ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Control Group ◽  
Neuroprotective Effects ◽  
Apoptosis Rate ◽  
Purple Sweet Potato

BACKGROUND: Purple sweet potato (Ipomoea Batatas L.) is one of the sources for anthocyanin, which promotes the health through antioxidant, anti-inflammatory, anti-cancer, neuroprotection, and anti-apoptosis activities. Oxidative stress has been shown to be the cause of apoptosis in ischemic stroke. AIM: The objective of this research was to delineate the pleiotropic effects of anthocyanin for neuroprotection during an acute stroke event. METHODS: Anthocyanin was extracted from Balinese cultivar of purple sweet potato and subsequently administered to rat models of induced ischemic stroke (labelled as treatment group), as well as a placebo (labelled as a control group). Several parameters were in turn evaluated, i.e. the activities of anti-apoptotic (Bcl-2) as well as pro-apoptotic (cytochrome c, caspase-3) molecules, and apoptosis rate. Bcl-2 levels were determined using the histochemical method, cytochrome c and caspase-3 via ELISA method, while apoptosis rate was measured by TdT-medicated Dutp-Nick End Labeling (TUNEL) assay. RESULTS: Bcl-2 expression demonstrated significantly higher Bcl-2 expression in the treatment compared with control group (median 31.2 vs. 1.1; p = 0.001). Accordingly, pro-apoptotic cytochrome c and caspase-3 levels were also found significantly lower in the treatment as opposed to control group (mean 4.17 vs. 8.06; p = 0.001; mean 3.81 vs. 8.02; p = 0.001). Ultimately, apoptosis rate was found markedly lower among treatment than control groups (mean 3.81 vs. control 21.97; p = 0.003). CONCLUSION: The results of this study indicated a significant neuroprotective effect of anthocyanin derived from Balinese cultivar of PSP. Anthocyanin was able to increase and reduce anti-apoptotic and pro-apoptotic protein levels, respectively, resulting in lesser cellular apoptotic rate when compared with placebo. The potential mechanism was thought mainly due to its anti-oxidant properties.

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