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.

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 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.

scholarly journals Gualou Guizhi Granule Suppresses LPS-induced Inflammatory Response of Microglia and Protects Against Microglial-Mediated Neurotoxicity in HT22 via Akt/NF-κB Signaling Pathways

2020 ◽  
Author(s):  
Yuqin Zhang ◽  
Yaojun Liu ◽  
Liming Fan ◽  
Lihong Nan ◽  
Wei Xu ◽  
...  
Keyword(s):  
Conditioned Medium ◽  
Neuronal Apoptosis ◽  
Neuroprotective Effect ◽  
Microglial Cells ◽  
Nuclear Factor ◽  
Ht22 Cells ◽  
Nuclear Factor Kappa ◽  
Bv2 Cells ◽  
Bv2 Microglia ◽  
Bv2 Microglial Cells

Abstract Background Neuroinflammation plays a crucial part in the commence and advancement of ischemic stroke. Gualou Guizhi Granule (GLGZG) is known to exhibit well neuroprotective effect, but it is not known whether GLGZG can regulate inflammatory process at the cellular level in BV2 microglia cells and protect against microglial-mediated neurotoxicity in neurons. Herein, we aimed to investigate the anti-inflammatory effects of GLGZG on BV2 microglia cells and protection against microglial-mediated neurotoxicity in neurons. Methods Cell model of neuroinflammation was constructed by lipopolysaccharide (LPS) to observe the effect of GLGZG in the presence or absence of GLGZG. The production of nitric oxide (NO), inflammatory mediators were detected. Moreover, potential mechanisms associated with anti-inflammatory effect, such as inhibition of microglial activation, the nuclear factor kappa B (NF-κB) were also investigated. In addition, to prove whether GLGZG protects against microglial-mediated neurotoxicity, neuronal HT22 cells were cultured in conditioned medium. And cell survivability, neuronal apoptosis of HT22 were evaluated. Results It was found that a main regulator of inflammation, NO, is suppressed by GLGZG in BV2 microglial cells. Moreover, GLGZG dose-dependently decreased the mRNA and protein levels of inducible NO synthase (iNOS) in LPS-stimulated BV2 cells. Additionally, GLGZG inhibited the expression and secretion of proinflammatory cytokines in BV2 microglial cells. And, GLGZG inhibited LPS-activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) in BV2 microglial cells at the intracellular level. GLGZG negatively affected Akt phosphorylation: phosphorylated forms of Akt decreased. To check whether GLGZG protects against microglial-mediated neurotoxicity, neuronal HT22 cells were incubated in the conditioned medium. GLGZG showed a neuroprotective effect by promoting cell survivability, suppressing neuronal apoptosis. Conclusions GLGZG exerted its potential effects on suppressing inflammatory responses in LPS-induced BV2 cells by attenuating NF-κB and Akt pathways. In addition, GLGZG could protect against microglial-mediated neurotoxicity in HT22.

scholarly journals Danggui-Shaoyao-San (DSS) Ameliorates Cerebral Ischemia-Reperfusion Injury via Activating SIRT1 Signaling and Inhibiting NADPH Oxidases

2021 ◽  
Vol 12 ◽  
Author(s):  
Yunxia Luo ◽  
Hansen Chen ◽  
Bun Tsoi ◽  
Qi Wang ◽  
Jiangang Shen
Keyword(s):  
Ischemic Stroke ◽  
Reperfusion Injury ◽  
Aqueous Extract ◽  
Nitrosative Stress ◽  
Ischemia Reperfusion Injury ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Ethanol Extract ◽  
Dependent Manner ◽  
Neuroprotective Effects

Danggui-Shayao-San (DSS) is a famous Traditional Chinese Medicine formula that used for treating pain disorders and maintaining neurological health. Recent studies indicate that DSS has neuroprotective effects against ischemic brain damage but its underlining mechanisms remain unclear. Herein, we investigated the neuroprotective mechanisms of DSS for treating ischemic stroke. Adult male Sprague-Dawley (S.D.) rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) plus 22 h of reperfusion. Both ethanol extract and aqueous extract of DSS (12 g/kg) were orally administrated into the rats at 30 min prior to MCAO ischemic onset. We found that 1) ethanol extract of DSS, instead of aqueous extract, reduced infarct sizes and improved neurological deficit scores in the post-ischemic stroke rats; 2) Ethanol extract of DSS down-regulated the expression of the cleaved-caspase 3 and Bax, up-regulated bcl-2 and attenuated apoptotic cell death in the ischemic brains; 3) Ethanol extract of DSS decreased the production of superoxide and peroxynitrite; 4) Ethanol extract of DSS significantly down-regulated the expression of p67phox but has no effect on p47phox and iNOS statistically. 5) Ethanol extract of DSS significantly up-regulated the expression of SIRT1 in the cortex and striatum of the post-ischemic brains; 6) Co-treatment of EX527, a SIRT1 inhibitor, abolished the DSS’s neuroprotective effects. Taken together, DSS could attenuate oxidative/nitrosative stress and inhibit neuronal apoptosis against cerebral ischemic-reperfusion injury via SIRT1-dependent manner.

scholarly journals trans-Cinnamaldehyde Inhibits Microglial Activation and Improves Neuronal Survival against Neuroinflammation in BV2 Microglial Cells with Lipopolysaccharide Stimulation

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Yan Fu ◽  
Pin Yang ◽  
Yang Zhao ◽  
Liqing Zhang ◽  
Zhangang Zhang ◽  
...  
Keyword(s):  
Neurodegenerative Disorders ◽  
Microglial Activation ◽  
Neuronal Damage ◽  
Neuronal Survival ◽  
Microglial Cells ◽  
Neuroprotective Effects ◽  
Bv2 Cells ◽  
Parkinson’S Diseases ◽  
Cox 2 ◽  
Bv2 Microglial Cells

Background.Microglial activation contributes to neuroinflammation and neuronal damage in neurodegenerative disorders including Alzheimer’s and Parkinson’s diseases. It has been suggested that neurodegenerative disorders may be improved if neuroinflammation can be controlled.trans-cinnamaldehyde (TCA) isolated from the stem bark ofCinnamomum cassiapossesses potent anti-inflammatory capability; we thus tested whether TCA presents neuroprotective effects on improving neuronal survival by inhibiting neuroinflammatory responses in BV2 microglial cells.Results.To determine the molecular mechanism behind TCA-mediated neuroprotective effects, we assessed the effects of TCA on lipopolysaccharide- (LPS-) induced proinflammatory responses in BV2 microglial cells. While LPS potently induced the production and expression upregulation of proinflammatory mediators, including NO, iNOS, COX-2, IL-1β, and TNF-α, TCA pretreatment significantly inhibited LPS-induced production of NO and expression of iNOS, COX-2, and IL-1βand recovered the morphological changes in BV2 cells. TCA markedly attenuated microglial activation and neuroinflammation by blocking nuclear factor kappa B (NF-κB) signaling pathway. With the aid of microglia and neuron coculture system, we showed that TCA greatly reduced LPS-elicited neuronal death and exerted neuroprotective effects.Conclusions.Our results suggest that TCA, a natural product, has the potential of being used as a therapeutic agent against neuroinflammation for ameliorating neurodegenerative disorders.

scholarly journals Neuroprotective Effects of Hesperetin in Regulating Microglia Polarization after Ischemic Stroke by Inhibiting TLR4/NF-κB Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Jiawen Zhang ◽  
Hao Jiang ◽  
Fang Wu ◽  
Xiaofei Chi ◽  
Yu Pang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Nerve Repair ◽  
Artery Occlusion ◽  
Sham Operation ◽  
Mrna Levels ◽  
Neuroprotective Effects ◽  
Sham Operation Group ◽  
Bv2 Cells ◽  
Tnf Α

This study aimed to explore the influence of hesperidin on the polarization of microglia to clarify the key mechanism of regulating the polarization of M2 microglia. C57BL/6 mice were randomly divided into middle cerebral artery occlusion model group (MCAO group), MCAO + hesperidin treatment group (MCAO + hesperidin group), and sham group (sham operation group). The mice were assessed with neurological scores for their functional status. 2,3,5-Triphenyltetrazole chloride (TTC) was used to determine the volume of cerebral infarction. Hematoxylin and eosin (H&E) staining was performed to detect brain loss. The system with 1% O2, 5% CO2, and 92% N2 was applied to establish BV2 in vitro model induced by MCAO. TNF-α, IL-1β, TGF-β, and IL-10 levels of cytokines in the supernatant were detected by ELISA. RT-qPCR was used to detect mRNA levels of M1 iNOS, CD11b, CD32, and CD86, and mRNA levels of M2 CD206, Arg-1, and TGF-β. The Iba-1, iNOS, and Arg-1 of microglia and protein levels of TLR4 and p-NF-κB related to the pathway were detected by Western blot. After treatment with hesperidin, BV2 cells induced by MCAO in vitro can reduce the proinflammatory cytokines of TNF-α and IL-1β significantly, further upregulating anti-inflammatory cytokines of TGF-β, IL-10 while inhibiting TLR4 and p-NF-κB expression. The MCAO-induced BV2 cells treated by TLR-4 inhibitor TAK-242 and NF-κB inhibitor BAY 11-7082 had similar polarization effects to those treated with hesperidin. This study found that hesperetin gavage treatment can improve the neurological deficit and regulate the polarization of microglia in MCAO mice. In vitro experiments further verified that hesperidin plays a neuroprotective role by inhibiting the TLR4-NF-κB pathway, thus providing new targets and strategies for neuroprotection and nerve repair after ischemic stroke.

scholarly journals Chemical Identification of Isoflavonoids from a Termite-Associated Streptomyces sp. RB1 and Their Neuroprotective Effects in Murine Hippocampal HT22 Cell Line

2018 ◽  
Vol 19 (9) ◽  
pp. 2640 ◽  
Author(s):  
Seoung Lee ◽  
Ji Song ◽  
Jae-Hyoung Song ◽  
Hyun-Jeong Ko ◽  
Ji Baek ◽  
...  
Keyword(s):  
Cell Line ◽  
Neuronal Damage ◽  
2D Nmr ◽  
Neuroprotective Effects ◽  
Associated Bacteria ◽  
Streptomyces Sp ◽  
Lead Compounds ◽  
Ros Accumulation ◽  
Ht22 Cell ◽  
Line Compound

Insect-associated bacteria have been recognized as a very promising natural resource for discovering bioactive secondary metabolites with diverse pharmacological effects. One new isoflavonoid glycoside, termisoflavone D (1), together with seven known isoflavonoids (2–8), were identified from MeOH extracts of the fungus-growing termite-associated Streptomyces sp. RB1. The chemical structure of the new compound 1 was elucidated using comprehensive spectroscopic methods including 1D and 2D NMR, along with LC/MS analysis. The existence of two rhamnose moieties in 1 was determined with comparative NMR analysis, and the absolute configuration was elucidated using chemical reactions. The neuroprotective activities of compounds 1–8 were thoroughly investigated using the murine hippocampal HT22 cell line. Compound 5 prevented glutamate-induced HT22 cell death by blocking intracellular reactive oxygen species (ROS) accumulation. The present study provides the first experimental evidence for the potential use of isoflavonoids from termite-associated bacteria as lead compounds that can prevent neuronal damage induced by glutamate.

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 Neuroprotective Effects of Bikaverin on H2O2-Induced Oxidative Stress Mediated Neuronal Damage in SH-SY5Y Cell Line

2014 ◽  
Vol 34 (7) ◽  
pp. 973-985 ◽  
Author(s):  
D. Nirmaladevi ◽  
M. Venkataramana ◽  
S. Chandranayaka ◽  
A. Ramesha ◽  
N. M. Jameel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Line ◽  
Neuronal Damage ◽  
Neuroprotective Effects

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.

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