scholarly journals American Ginseng (Panax quinquefolium L.) as a Source of Bioactive Phytochemicals with Pro-Health Properties

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1041 ◽  
Author(s):  
Daria Szczuka ◽  
Adriana Nowak ◽  
Małgorzata Zakłos-Szyda ◽  
Ewa Kochan ◽  
Grażyna Szymańska ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Contractile Function ◽  
Neuronal Damage ◽  
American Ginseng ◽  
Anxiolytic Activity ◽  
Panax Quinquefolium ◽  
Cardiac Contractile Function ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Model Of Alzheimer’S Disease

Panax quinquefolium L. (American Ginseng, AG) is an herb characteristic for regions of North America and Asia. Due to its beneficial properties it has been extensively investigated for decades. Nowadays, it is one of the most commonly applied medical herbs worldwide. Active compounds of AG are ginsenosides, saponins of the glycosides group that are abundant in roots, leaves, stem, and fruits of the plant. Ginsenosides are suggested to be primarily responsible for health-beneficial effects of AG. AG acts on the nervous system; it was reported to improve the cognitive function in a mouse model of Alzheimer’s disease, display anxiolytic activity, and neuroprotective effects against neuronal damage resulting from ischemic stroke in animals, demonstrate anxiolytic activity, and induce neuroprotective effects against neuronal damage in ischemic stroke in animals. Administration of AG leads to inhibition of hypertrophy in heart failure by regulation of reactive oxygen species (ROS) in mice as well as depletion of cardiac contractile function in rats. It also has an anti-diabetic and anti-obesity potential as it increases insulin sensitivity and inhibits formation of adipose tissue. AG displays anti-cancer effect by induction of apoptosis of cancer cells and reducing local inflammation. It exerts antimicrobial effects against several pathogenic strains of bacteria. Therefore, AG presents a high potential to induce beneficial health effects in humans and should be further explored to formulate precise nutritional recommendations, as well as to assess its value in prevention and therapy of some disorders, including cancer.

Neuroprotection via AT2 receptor agonists in ischemic stroke

2018 ◽  
Vol 132 (10) ◽  
pp. 1055-1067 ◽  
Author(s):  
Douglas M. Bennion ◽  
U. Muscha Steckelings ◽  
Colin Sumners
Keyword(s):  
Ischemic Stroke ◽  
Neuronal Damage ◽  
Recombinant Tissue Plasminogen Activator ◽  
Neurological Deficits ◽  
At2 Receptor ◽  
Neuroprotective Effects ◽  
Receptor Agonists ◽  
Stroke Epidemiology ◽  
The Brain

Stroke is a devastating disease that afflicts millions of people each year worldwide. Ischemic stroke, which accounts for ~88% of cases, occurs when blood supply to the brain is decreased, often because of thromboembolism or atherosclerotic occlusion. This deprives the brain of oxygen and nutrients, causing immediate, irreversible necrosis within the core of the ischemic area, but more delayed and potentially reversible neuronal damage in the surrounding brain tissue, the penumbra. The only currently approved therapies for ischemic stroke, the thrombolytic agent recombinant tissue plasminogen activator (rtPA) and the endovascular clot retrieval/destruction processes, are aimed at restoring blood flow to the infarcted area, but are only available for a minority of patients and are not able in most cases to completely restore neurological deficits. Consequently, there remains a need for agents that will protect neurones against death following ischemic stroke. Here, we evaluate angiotensin II (Ang II) type 2 (AT2) receptor agonists as a possible therapeutic target for this disease. We first provide an overview of stroke epidemiology, pathophysiology, and currently approved therapies. We next review the large amount of preclinical evidence, accumulated over the past decade and a half, which indicates that AT2 receptor agonists exert significant neuroprotective effects in various animal models, and discuss the potential mechanisms involved. Finally, after discussing the challenges of delivering blood–brain barrier (BBB) impermeable AT2 receptor agonists to the infarcted areas of the brain, we summarize the evidence for and against the development of these agents as a promising therapeutic strategy for ischemic stroke.

scholarly journals Sirtuin 3 Mediates Neuroprotection of Ketones against Ischemic Stroke

2015 ◽  
Vol 35 (11) ◽  
pp. 1783-1789 ◽  
Author(s):  
Junxiang Yin ◽  
Pengcheng Han ◽  
Zhiwei Tang ◽  
Qingwei Liu ◽  
Jiong Shi
Keyword(s):  
Ischemic Stroke ◽  
Ketone Bodies ◽  
Infarct Volume ◽  
Field Tests ◽  
Underlying Mechanism ◽  
Sirtuin 3 ◽  
Neuroprotective Effects ◽  
Beneficial Effects ◽  
Beta Hydroxybutyrate

Stroke is one of the leading causes of death. Growing evidence indicates that ketone bodies have beneficial effects in treating stroke, but their underlying mechanism remains unclear. Our previous study showed ketone bodies reduced reactive oxygen species by using NADH as an electron donor, thus increasing the NAD+/NADH ratio. In this study, we investigated whether mitochondrial NAD+-dependent Sirtuin 3 (SIRT3) could mediate the neuroprotective effects of ketone bodies after ischemic stroke. We injected mice with either normal saline or ketones (beta-hydroxybutyrate and acetoacetate) at 30 minutes after ischemia induced by transient middle cerebral artery (MCA) occlusion. We found that ketone treatment enhanced mitochondria function, reduced oxidative stress, and therefore reduced infarct volume. This led to improved neurologic function after ischemia, including the neurologic score and the performance in Rotarod and open field tests. We further showed that ketones' effects were achieved by upregulating NAD+-dependent SIRT3 and its downstream substrates forkhead box O3a (FoxO3a) and superoxide dismutase 2 (SOD2) in the penumbra region since knocking down SIRT3 in vitro diminished ketones' beneficial effects. These results provide us a foundation to develop novel therapeutics targeting this SIRT3-FoxO3a-SOD2 pathway.

scholarly journals MiR-137 Boosts the Neuroprotective Effect of Endothelial Progenitor Cell Derived-Exosomes in Oxyhemoglobin Treated SH-SY5Y Cells Partially via COX2/PGE2 Pathway

2020 ◽  
Author(s):  
Yuchen Li ◽  
Jinju Wang ◽  
Shuzhen Chen ◽  
Pei Wu ◽  
Shancai Xu ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Ischemic Stroke ◽  
Glutathione Peroxidase ◽  
Iron Overload ◽  
Mitochondrial Dysfunction ◽  
Neuroprotective Effect ◽  
Endothelial Progenitor ◽  
Neuroprotective Effects ◽  
Protection Mechanism ◽  
Beneficial Effects

Abstract Background: We have previously verified the beneficial effects of exosomes from endothelial progenitor cells (EPC-EXs) in ischemic stroke. However, the effects of EPC-EXs in hemorrhagic stroke have not been investigated. Additionally, miR-137 is reported to regulate ferroptosis and to be involved in the neuroprotection against ischemic stroke. Hence, the present work explored the effects of miR-137-overexpressing EPC-EXs on apoptosis, mitochondrial dysfunction, and ferroptosis in oxyhemoglobin (oxyHb)-injured SH-SY5Y cells. Methods: The lentiviral miR-137 was transfected into EPCs and then the EPC-EXs were collected. RT-PCR was used to detect the miR-137 level in EPCs, EXs and neurons. The uptake mechanisms of EPC-EXs in SH-SY5Y cells were explored by the co-incubation of Dynasore, Pitstop 2, Ly294002 and Genistein. After the transfection of different types of EPC-EXs, flow cytometry and expression of cytochrome c and cleaved caspase-3 were used to detect the apoptosis of oxyHb-injured neurons. Neuronal mitochondrial function was assessed by reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) depolarization, and cellular ATP content. Cell ferroptosis was measured by lipid peroxidation, iron overload, degradation of glutathione and glutathione peroxidase 4. Additionally, recombinational PGE2 was used to detect if activation of COX2/PGE2 pathway could reverse the protection of miR-137 overexpression.Results: The present work showed 1) EPC-EXs could be taken in by SH-SY5Y cells via caveolin-/clathrin-mediated pathways and macropinocytosis; 2) miR-137 was decreased in neurons after oxyHb treatment, and EXsmiR-137 could restore the miR-137 levels; 3) EXsmiR-137 worked better than EXs in reducing the number of apoptotic neurons and pro-apoptotic protein expression after oxyHb treatment; 4) EXsmiR-137 are more effective in improving the cellular MMP, ROS and ATP level; 5) EXsmiR-137, but not EXs, protected oxyHb-treated SH-SY5Y cells against lipid peroxidation, iron overload, degradation of glutathione and glutathione peroxidase 4; 6) EXsmiR-137 suppressed the expression of the COX2/PGE2 pathway, and activation of the pathway could partially reverse the neuroprotective effects of EXsmiR-137. Conclusion: MiR-137 overexpression boosts the neuroprotective effects of EPC-EXs against apoptosis and mitochondrial dysfunction in oxyHb-treated SH-SY5Y cells. Furthermore, EXsmiR-137 rather than EXs can restore the decrease in miR-137 levels and inhibit ferroptosis, and the protection mechanism might involve the miR-137-COX2/PGE2 signaling pathway.

scholarly journals MiR-137 Boosts the Neuroprotective Effect of Endothelial Progenitor Cell Derived-Exosomes in Oxyhemoglobin Treated SH-SY5Y Cells Partially via COX2/PGE2 Pathway

2020 ◽  
Author(s):  
Yuchen Li ◽  
Jinju Wang ◽  
Shuzhen Chen ◽  
Pei Wu ◽  
Shancai Xu ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Ischemic Stroke ◽  
Glutathione Peroxidase ◽  
Iron Overload ◽  
Mitochondrial Dysfunction ◽  
Neuroprotective Effect ◽  
Endothelial Progenitor ◽  
Neuroprotective Effects ◽  
Protection Mechanism ◽  
Beneficial Effects

Abstract Background: We have previously verified the beneficial effects of exosomes from endothelial progenitor cells (EPC-EXs) in ischemic stroke. However, the effects of EPC-EXs in hemorrhagic stroke have not been investigated. Additionally, miR-137 is reported to regulate ferroptosis and to be involved in the neuroprotection against ischemic stroke. Hence, the present work explored the effects of miR-137-overexpressing EPC-EXs on apoptosis, mitochondrial dysfunction, and ferroptosis in oxyhemoglobin (oxyHb)-injured neurons.Methods: The lentiviral miR-137 was transfected into EPCs and then the EPC-EXs were collected. RT-PCR was used to detect the miR-137 level in EPCs, EXs and neurons. The uptake mechanisms of EPC-EXs in neurons were explored by the co-incubation of Dynasore, Pitstop 2, Ly294002 and Genistein. After the transfection of different types of EPC-EXs, flow cytometry and expression of cytochrome c and cleaved caspase-3 were used to detect the apoptosis of oxyHb-injured neurons. Neuronal mitochondrial function was assessed by reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) depolarization, and cellular ATP content. Cell ferroptosis was measured by lipid peroxidation, iron overload, degradation of glutathione and glutathione peroxidase 4. Additionally, recombinational PGE2 was used to detect if activation of COX2/PGE2 pathway could reverse the protection of miR-137 overexpression.Results: The present work showed 1) EPC-EXs could be taken in by SH-SY5Y cells via caveolin-/clathrin-mediated pathways and macropinocytosis; 2) miR-137 was decreased in neurons after oxyHb treatment, and EXs miR-137 could restore the miR-137 levels; 3) EXs miR-137 worked better than EXs in reducing the number of apoptotic neurons and pro-apoptotic protein expression after oxyHb treatment; 4) EXs miR-137 are more effective in improving the cellular MMP, ROS and ATP level; 5) EXs miR-137 , but not EXs, protected oxyHb-treated neurons against lipid peroxidation, iron overload, degradation of glutathione and glutathione peroxidase 4; 6) EXs miR-137 suppressed the expression of the COX2/PGE2 pathway, and activation of the pathway could partially reverse the neuroprotective effects of EXs miR-137 .Conclusion: MiR-137 overexpression boosts the neuroprotective effects of EPC-EXs against apoptosis and mitochondrial dysfunction in oxyHb-treated neurons. Furthermore, EXs miR-137 rather than EXs can restore the decrease in miR-137 levels and inhibit ferroptosis, and the protection mechanism might involve the miR-137-COX2/PGE2 signaling pathway.

scholarly journals Inhibitory Effect of Gualou Guizhi Decoction on Microglial Inflammation and Neuron Injury by Promoting Anti-Inflammation via Targeting mmu-miR-155

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Haixia Hu ◽  
Xinghua Zhong ◽  
Xinjun Lin ◽  
Jinbo Yang ◽  
Xiaoqin Zhu
Keyword(s):  
Ischemic Stroke ◽  
Cell Line ◽  
Conditioned Medium ◽  
Neuronal Damage ◽  
Apoptotic Cell ◽  
Neuroprotective Effects ◽  
Ht22 Cells ◽  
Guizhi Decoction ◽  
Bv2 Cells ◽  
Microglial Inflammation

Gualou Guizhi decoction (GLGZD) treatment exerts neuroprotective effects and promotes spasticity following ischemic stroke. However, the molecular mechanism of GLGZD treatment on ischemic stroke remains unclear. Our previous study indicated that GLGZD ameliorates neuronal damage caused by secondary inflammatory injury induced by microglia. In the present study, we investigate the potential mechanism of GLGZD treatment on neuron damage induced by neuroinflammation via mmu-miR-155 in vitro. The HT22 cell line and the BV2 cell line were exposed to oxygen/glucose-deprive (OGD) conditions; the conditioned medium was prepared using the supernatants from OGD-stimulated BV2 cells after pretreating with GLGZD. Cell viability was determined by MTT assays; levels of released inflammatory cytokines were assessed using the BioPlex system. mmu-miR-155 and its targeting genes were detected using real-time reverse transcription polymerase chain reaction (RT-PCR). The expression of anti-inflammatory proteins was evaluated by Western blotting. DAPI staining was used to test the apoptotic cells. Our results showed that GLGZD pretreatment significantly induced IL10 release and decreased the production of TNF-α, IL6, and IFN-γ. In addition, GLGZD markedly attenuated mmu-miR-155 expression and its downstream SOCS1, SMAD2, SHIP1, and TAB2 expression levels. The DAPI-stained apoptotic cell death and caspase-3 activation in HT22 cells exposed to the conditioned medium were reversed by GLGZD treatment. Our findings suggested that GLGZD pretreatment downregulates the mmu-miR-155 signaling, which inhibits microglial inflammation, thereby resulting in the suppression of neuron apoptosis after OGD stress. The underlying mechanisms may provide the support for GLGZD treatment of cerebral ischemic injury.

scholarly journals miR-137 boosts the neuroprotective effect of endothelial progenitor cell-derived exosomes in oxyhemoglobin-treated SH-SY5Y cells partially via COX2/PGE2 pathway

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuchen Li ◽  
Jinju Wang ◽  
Shuzhen Chen ◽  
Pei Wu ◽  
Shancai Xu ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Ischemic Stroke ◽  
Glutathione Peroxidase ◽  
Iron Overload ◽  
Mitochondrial Dysfunction ◽  
Neuroprotective Effect ◽  
Endothelial Progenitor ◽  
Neuroprotective Effects ◽  
Protection Mechanism ◽  
Beneficial Effects

Abstract Background We have previously verified the beneficial effects of exosomes from endothelial progenitor cells (EPC-EXs) in ischemic stroke. However, the effects of EPC-EXs in hemorrhagic stroke have not been investigated. Additionally, miR-137 is reported to regulate ferroptosis and to be involved in the neuroprotection against ischemic stroke. Hence, the present work explored the effects of miR-137-overexpressing EPC-EXs on apoptosis, mitochondrial dysfunction, and ferroptosis in oxyhemoglobin (oxyHb)-injured SH-SY5Y cells. Methods The lentiviral miR-137 was transfected into EPCs and then the EPC-EXs were collected. RT-PCR was used to detect the miR-137 level in EPCs, EXs, and neurons. The uptake mechanisms of EPC-EXs in SH-SY5Y cells were explored by the co-incubation of Dynasore, Pitstop 2, Ly294002, and Genistein. After the transfection of different types of EPC-EXs, flow cytometry and expression of cytochrome c and cleaved caspase-3 were used to detect the apoptosis of oxyHb-injured neurons. Neuronal mitochondrial function was assessed by reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP) depolarization, and cellular ATP content. Cell ferroptosis was measured by lipid peroxidation, iron overload, degradation of glutathione, and glutathione peroxidase 4. Additionally, recombinational PGE2 was used to detect if activation of COX2/PGE2 pathway could reverse the protection of miR-137 overexpression. Results The present work showed (1) EPC-EXs could be taken in by SH-SY5Y cells via caveolin-/clathrin-mediated pathways and macropinocytosis; (2) miR-137 was decreased in neurons after oxyHb treatment, and EXsmiR-137 could restore the miR-137 levels; (3) EXsmiR-137 worked better than EXs in reducing the number of apoptotic neurons and pro-apoptotic protein expression after oxyHb treatment; (4) EXsmiR-137 are more effective in improving the cellular MMP, ROS, and ATP level; (5) EXsmiR-137, but not EXs, protected oxyHb-treated SH-SY5Y cells against lipid peroxidation, iron overload, degradation of glutathione, and glutathione peroxidase 4; and (6) EXsmiR-137 suppressed the expression of the COX2/PGE2 pathway, and activation of the pathway could partially reverse the neuroprotective effects of EXsmiR-137. Conclusion miR-137 overexpression boosts the neuroprotective effects of EPC-EXs against apoptosis and mitochondrial dysfunction in oxyHb-treated SH-SY5Y cells. Furthermore, EXsmiR-137 rather than EXs can restore the decrease in miR-137 levels and inhibit ferroptosis, and the protection mechanism might involve the miR-137-COX2/PGE2 signaling pathway.

scholarly journals Design, Synthesis and Biological Evaluation of Indoline Derivatives as Multifunctional Agents for the Treatment of Ischemic Stroke

2021 ◽  
Author(s):  
Shuaishuai Du ◽  
Fan Jin ◽  
Jiaming Li ◽  
Xiaodong Ma ◽  
Hongwei Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Neuronal Damage ◽  
Glucose Deprivation ◽  
Biological Evaluation ◽  
Artery Occlusion ◽  
Raw 264.7 Cells ◽  
Protective Effects ◽  
Neuroprotective Agents ◽  
Neuroprotective Effects ◽  
Design Synthesis

Abstract In this work, a series of indoline derivatives as multifunctional neuroprotective agents for battling ischemic stroke were designed, synthesized, and biologically evaluated. In antioxidant assay, all compounds showed significant protective effects against H2O2-induced death of RAW 264.7 cells. In oxygen glucose deprivation/reperfusion (OGD/R)-induced neuronal damage, some compounds significantly elevated the cell survival rate. Among them, 7i, 7j and 7r exerted comparable neuroprotective effects to Ifenprodil, and exhibited binding affinity to N-methyl-D-aspartic acid receptors 2B (NMDA-GluN2B). At the concentrations of 0.1, 1 and 10 μM, 7i, 7j and 7r dose-dependently lowered the LPS-induced secretion of inflammatory cytokines, including TNF-α, IL-6 and NO, by BV-2 cells. Importantly, 7i and 7j can dramatically reduce the cerebral infarction rate and improve neurological deficit scores in middle cerebral artery occlusion (MCAO) rat model. As demonstrated by the above results, 7i and 7j are potential neuroprotective agents for the treatment of ischemic stroke.

scholarly journals Upregulation of CREB1 and FOXO1 transcription factor pathways in Neuregulin-1 mediated neuroprotection following ischemic stroke

2021 ◽  
Author(s):  
Kimberly R. Bennett ◽  
Monique C. Surles-Zeigler ◽  
Cathrerine J. Augello ◽  
Etchi Ako ◽  
Victor G.J. Rodgers ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Ischemic Stroke ◽  
Stress Responses ◽  
Molecular Mechanisms ◽  
Neuronal Damage ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Artery Occlusion ◽  
Neuroprotective Effects ◽  
Neuregulin 1

Neuregulin-1 (NRG-1) is growth factor that has been investigated for its neuroprotective properties following ischemic stroke. While NRG-1 has shown significant promise in preventing neuronal damage following stroke, the mechanisms behind its neuroprotective effects are unclear. The goal of this research was to investigate the effects of NRG-1 treatment on ischemia-induced gene expression profiles following a permanent middle cerebral artery occlusion (MCAO) in rats. Rats were sacrificed twelve hours following MCAO and either vehicle or NRG-1 treatment. RNA extracted from the peri-infarct cortex of the brain was hybridized to an Affymetrix Rat Genome 2.0st Microarray Gene Chip. Data were analyzed using the Affymetrix Transcriptome Analysis Console (TAC) 4.0 software and the STRING Protein-Protein Interaction Networks database.  Our results showed that NRG?1 delivery increased the regulation of pro-survival genes. Most notably, NRG-1 treatment upregulated the CREB1 and FOXO1 transcription factor pathways which are involved in increasing anti-inflammatory and cell proliferation responses and decreasing apoptosis and oxidative stress responses, respectively. Luminex multiplex transcription factor assays demonstrated that the activities of CREB1 and FOXO1 were increased by NRG-1 treatment with MCAO. These findings provide novel insight into the molecular mechanisms involved in NRG-1 mediated neuroprotection.

Heat Shock Protein 70 kDa as a Target for Diagnostics and Therapy of Cardiovascular and Cerebrovascular Diseases

2019 ◽  
Vol 25 (6) ◽  
pp. 710-714 ◽  
Author(s):  
Ekaterina V. Konstantinova ◽  
Natalia S. Chipigina ◽  
Marina H. Shurdumova ◽  
E.I. Kovalenko ◽  
Alexander M. Sapozhnikov
Keyword(s):  
Myocardial Infarction ◽  
Ischemic Stroke ◽  
Heat Shock ◽  
Cerebrovascular Diseases ◽  
Peripheral Blood Lymphocytes ◽  
Neuroprotective Effects ◽  
Adverse Conditions ◽  
Shock Proteins ◽  
Diagnostics And Therapy ◽  
Main Factor

Acute focal ischemia is a main factor of pathogenesis of a number of widespread cardiovascular and cerebrovascular diseases, in particular, myocardial infarction and ischemic stroke. It is known that under the conditions of ischemia expression of intracellular heat shock proteins (HSPs), especially HSP70, grows greatly irrespective of the cell type. This stress-induced cell response is connected with cytoprotective properties of HSP70. The protective functions of HSP70 contribute to the cell survival under adverse conditions and inhibit development of programmed cell death. It was shown, that the level of HSP70 increases in cardiomyocytes and brain cells in response to ischemia, that was connected with cardioprotective and neuroprotective effects. Besides, in recent years, clinical studies of HSP70 have demonstrated elevated level of HSP70 in peripheral blood lymphocytes in groups of patients with ischemic stroke and myocardial infarction. This review indicates that HSP70 can serve as a target for developing new approaches to diagnostics and therapy of cardiovascular and cerebrovascular diseases.

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