scholarly journals Formulated Chinese Medicine Shaoyao Gancao Tang Reduces Tau Aggregation and Exerts Neuroprotection through Anti-Oxidation and Anti-Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-16 ◽  
Author(s):  
I-Cheng Chen ◽  
Te-Hsien Lin ◽  
Yu-Hsuan Hsieh ◽  
Chih-Ying Chao ◽  
Yih-Ru Wu ◽  
...  
Keyword(s):  
Cell Model ◽  
Neuronal Cell Death ◽  
Herbal Medicines ◽  
Neuronal Cell ◽  
Tau Proteins ◽  
No Production ◽  
Study Results ◽  
Apoptosis Protein ◽  
Anti Inflammatory ◽  
Protein Array Analysis

Misfolded tau proteins induce accumulation of free radicals and promote neuroinflammation by activating microglia-releasing proinflammatory cytokines, leading to neuronal cell death. Traditional Chinese herbal medicines (CHMs) have been widely used in clinical practice to treat neurodegenerative diseases associated with oxidative stress and neuroinflammation. This study examined the neuroprotection effects of formulated CHMs Bai-Shao (made of Paeonia lactiflora), Gan-Cao (made of Glycyrrhiza uralensis), and Shaoyao Gancao Tang (SG-Tang, made of P. lactiflora and G. uralensis at 1 : 1 ratio) in cell model of tauopathy. Our results showed that SG-Tang displayed a greater antioxidative and antiaggregation effect than Bai-Shao and Gan-Cao and a stronger anti-inflammatory activity than Bai-Shao but similar to Gan-Cao. In inducible 293/SH-SY5Y cells expressing proaggregant human tau repeat domain (ΔK280 tauRD), SG-Tang reduced tau misfolding and reactive oxygen species (ROS) level in ΔK280 tauRD 293 cells and promoted neurite outgrowth in ΔK280 tauRD SH-SY5Y cells. Furthermore, SG-Tang displayed anti-inflammatory effects by reducing nitric oxide (NO) production in mouse BV-2 microglia and increased cell viability of ΔK280 tauRD-expressing SH-SY5Y cells inflamed by BV-2 conditioned medium. To uncover the neuroprotective mechanisms of SG-Tang, apoptosis protein array analysis of inflamed tau expressing SH-SY5Y cells was conducted and the suppression of proapoptotic proteins was confirmed. In conclusion, SG-Tang displays neuroprotection by exerting antioxidative and anti-inflammatory activities to suppress neuronal apoptosis in human tau cell models. The study results lay the base for future applications of SG-Tang on tau animal models to validate its effect of reducing tau misfolding and potential disease modification.

scholarly journals Effects of S-2474, a novel nonsteroidal anti-inflammatory drug, on amyloid β protein-induced neuronal cell death

2001 ◽  
Vol 134 (3) ◽  
pp. 673-681 ◽  
Author(s):  
Tatsurou Yagami ◽  
Keiichi Ueda ◽  
Kenji Asakura ◽  
Toshiyuki Sakaeda ◽  
Takayuki Kuroda ◽  
...  
Keyword(s):  
Cell Death ◽  
Neuronal Cell Death ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Amyloid Β Protein ◽  
Inflammatory Drug ◽  
Β Protein ◽  
Anti Inflammatory

scholarly journals Mesenchymal Stem Cells (MSCs) Coculture Protects [Ca2+]i Orchestrated Oxidant Mediated Damage in Differentiated Neurons In Vitro

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 250 ◽  
Author(s):  
Adel Alhazzani ◽  
Prasanna Rajagopalan ◽  
Zaher Albarqi ◽  
Anantharam Devaraj ◽  
Mohamed Hessian Mohamed ◽  
...  
Keyword(s):  
Cell Death ◽  
Transforming Growth Factor ◽  
Neuronal Cells ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Apoptotic Cells ◽  
Sequence Of Events ◽  
Cox 2 ◽  
Anti Inflammatory

Cell-therapy modalities using mesenchymal stem (MSCs) in experimental strokes are being investigated due to the role of MSCs in neuroprotection and regeneration. It is necessary to know the sequence of events that occur during stress and how MSCs complement the rescue of neuronal cell death mediated by [Ca2+]i and reactive oxygen species (ROS). In the current study, SH-SY5Y-differentiated neuronal cells were subjected to in vitro cerebral ischemia-like stress and were experimentally rescued from cell death using an MSCs/neuronal cell coculture model. Neuronal cell death was characterized by the induction of proinflammatory tumor necrosis factor (TNF)-α, interleukin (IL)-1β and -12, up to 35-fold with corresponding downregulation of anti-inflammatory cytokine transforming growth factor (TGF)-β, IL-6 and -10 by approximately 1 to 7 fold. Increased intracellular calcium [Ca2+]i and ROS clearly reaffirmed oxidative stress-mediated apoptosis, while upregulation of nuclear factor NF-B and cyclo-oxygenase (COX)-2 expressions, along with ~41% accumulation of early and late phase apoptotic cells, confirmed ischemic stress-mediated cell death. Stressed neuronal cells were rescued from death when cocultured with MSCs via increased expression of anti-inflammatory cytokines (TGF-β, 17%; IL-6, 4%; and IL-10, 13%), significantly downregulated NF-B and proinflammatory COX-2 expression. Further accumulation of early and late apoptotic cells was diminished to 23%, while corresponding cell death decreased from 40% to 17%. Low superoxide dismutase 1 (SOD1) expression at the mRNA level was rescued by MSCs coculture, while no significant changes were observed with catalase (CAT) and glutathione peroxidase (GPx). Interestingly, increased serotonin release into the culture supernatant was proportionate to the elevated [Ca2+]i and corresponding ROS, which were later rescued by the MSCs coculture to near normalcy. Taken together, all of these results primarily support MSCs-mediated modulation of stressed neuronal cell survival in vitro.

From tau phosphorylation to tau aggregation: what about neuronal death?

2010 ◽  
Vol 38 (4) ◽  
pp. 967-972 ◽  
Author(s):  
Luc Buée ◽  
Laëtitia Troquier ◽  
Sylvie Burnouf ◽  
Karim Belarbi ◽  
Anneke Van der Jeugd ◽  
...  
Keyword(s):  
Cell Death ◽  
Cognitive Impairment ◽  
Neurodegenerative Disorders ◽  
Neuronal Death ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Tau Phosphorylation ◽  
Tau Proteins ◽  
Phosphorylated Tau ◽  
Sequence Of Events

Tau pathology is characterized by intracellular aggregates of abnormally and hyperphosphorylated tau proteins. It is encountered in many neurodegenerative disorders, but also in aging. These neurodegenerative disorders are referred to as tauopathies. Comparative biochemistry of the tau aggregates shows that they differ in both tau isoform phosphorylation and content, which enables a molecular classification of tauopathies. In conditions of dementia, NFD (neurofibrillary degeneration) severity is correlated to cognitive impairment and is often considered as neuronal death. Using tau animal models, analysis of the kinetics of tau phosphorylation, aggregation and neuronal death in parallel to electrophysiological and behavioural parameters indicates a disconnection between cognition deficits and neuronal cell death. Tau phosphorylation and aggregation are early events followed by cognitive impairment. Neuronal death is not observed before the oldest ages. A sequence of events may be the formation of toxic phosphorylated tau species, their aggregation, the formation of neurofibrillary tangles (from pre-tangles to ghost tangles) and finally neuronal cell death. This sequence will last from 15 to 25 years and one can ask whether the aggregation of toxic phosphorylated tau species is a protection against cell death. Apoptosis takes 24 h, but NFD lasts for 24 years to finally kill the neuron or rather to protect it for more than 20 years. Altogether, these data suggest that NFD is a transient state before neuronal death and that therapeutic interventions are possible at that stage.

scholarly journals Peroxisome Proliferator-Activated Receptors: “Key” Regulators of Neuroinflammation after Traumatic Brain Injury

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Philip F. Stahel ◽  
Wade R. Smith ◽  
Jay Bruchis ◽  
Craig H. Rabb
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Synthetic Cannabinoids ◽  
Experimental Studies ◽  
Neuronal Cell ◽  
Peroxisome Proliferator ◽  
Therapeutic Concept ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors

Traumatic brain injury is characterized by neuroinflammatory pathological sequelae which contribute to brain edema and delayed neuronal cell death. Until present, no specific pharmacological compound has been found, which attenuates these pathophysiological events and improves the outcome after head injury. Recent experimental studies suggest that targeting peroxisome proliferator-activated receptors (PPARs) may represent a new anti-inflammatory therapeutic concept for traumatic brain injury. PPARs are “key” transcription factors which inhibit NFκBactivity and downstream transcription products, such as proinflammatory and proapoptotic cytokines. The present review outlines our current understanding of PPAR-mediated neuroprotective mechanisms in the injured brain and discusses potential future anti-inflammatory strategies for head-injured patients, with an emphasis on the putative beneficial combination therapy of synthetic cannabinoids (e.g., dexanabinol) with PPARαagonists (e.g., fenofibrate).

scholarly journals UPEI-400, a Conjugate of Lipoic Acid and Scopoletin, Mediates Neuroprotection in a Rat Model of Ischemia/Reperfusion

2016 ◽  
Author(s):  
Barry J. Connell ◽  
Monique C. Saleh ◽  
Desikan Rajagopal ◽  
Tarek M. Saleh
Keyword(s):  
Cell Death ◽  
Lipoic Acid ◽  
Ischemia Reperfusion ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Covalent Bond ◽  
Male Rats ◽  
In Vivo Model ◽  
Naturally Occurring ◽  
Anti Inflammatory

Background: Previously, our laboratory has provided evidence that pre-administration of the antioxidant, lipoic acid covalently bonded to various naturally occurring antioxidants, enhanced neuroprotective capacity compared to the administration of lipoic acid on its own. The naturally occurring compound scopoletin, a coumarin derivative, has been shown in various in vitro studies to have both antioxidant and anti-inflammatory mechanism of actions. To date, the effect of scopoletin on neuronal cell death in an in vivo model of ischemia or ischemia-reperfusion has not been investigated. Therefore, the present investigation was designed to determine if scopoletin on its own, or a co-drug consisting of lipoic acid and scopoletin covalent bond, named UPEI-400, would be capable of demonstrating a similar neuroprotective efficacy. Methods: Using a rodent model of stroke in male rats (anesthetized with Inactin®; 100 mg/kg, iv), the middle cerebral artery was permanently occluded for 6 hours (pMCAO), or in separate animals, occluded for 30 min followed by 5.5 hrs of reperfusion (ischemia/reperfusion; I/R). Results: Pre-administration of either scopoletin or UPEI-400 significantly decreased infarct volume in the I/R model (p<0.05), but not in the pMCAO model of stroke. However, UPEI-400 was ~1000 times more potent as compared to scopoletin on its own. The optimal dose of UPEI-400 was then injected during the occlusion and at several time points during reperfusion and significant neuroprotection was observed for up to 150 mins following the start of reperfusion (p<0.05). Conclusion: The data suggest that synthetic combination of scopoletin with lipoic acid (UPEI-400) is a more effective neuroprotectant that either compound on their own. Also, since UPEI-400 was only effective in a model of I/R, it is possible that it may act to enhance neuronal antioxidant capacity and/or upregulate anti-inflammatory pathways to prevent the neuronal cell death.

scholarly journals Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH)

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Rebecca Heinz ◽  
Susan Brandenburg ◽  
Melina Nieminen-Kelhä ◽  
Irina Kremenetskaia ◽  
Philipp Boehm-Sturm ◽  
...  
Keyword(s):  
Cell Death ◽  
Brain Injury ◽  
Neuronal Cell Death ◽  
Treatment Strategies ◽  
Neuronal Cell ◽  
Surface Expression ◽  
Receptor Activation ◽  
Sham Operation ◽  
Secondary Brain Injury ◽  
Anti Inflammatory

Abstract Background Microglia-driven cerebral spreading inflammation is a key contributor to secondary brain injury after SAH. Genetic depletion or deactivation of microglia has been shown to ameliorate neuronal cell death. Therefore, clinically feasible anti-inflammatory approaches counteracting microglia accumulation or activation are interesting targets for SAH treatment. Here, we tested two different methods of interference with microglia-driven cerebral inflammation in a murine SAH model: (i) inflammatory preconditioning and (ii) pharmacological deactivation. Methods 7T-MRI-controlled SAH was induced by endovascular perforation in four groups of C57Bl/6 mice: (i) Sham-operation, (ii) SAH naïve, (iii) SAH followed by inflammatory preconditioning (LPS intraperitoneally), and (iv) SAH followed by pharmacological microglia deactivation (colony-stimulating factor-1 receptor-antagonist PLX3397 intraperitoneally). Microglia accumulation and neuronal cell death (immuno-fluorescence), as well as activation status (RT-PCR for inflammation-associated molecules from isolated microglia) were recorded at day 4 and 14. Toll-like receptor4 (TLR4) status was analyzed using FACS. Results Following SAH, significant cerebral spreading inflammation occurred. Microglia accumulation and pro-inflammatory gene expression were accompanied by neuronal cell death with a maximum on day 14 after SAH. Inflammatory preconditioning as well as PLX3397-treatment resulted in significantly reduced microglia accumulation and activation as well as neuronal cell death. TLR4 surface expression in preconditioned animals was diminished as a sign for receptor activation and internalization. Conclusions Microglia-driven cerebral spreading inflammation following SAH contributes to secondary brain injury. Two microglia-focused treatment strategies, (i) inflammatory preconditioning with LPS and (ii) pharmacological deactivation with PLX3397, led to significant reduction of neuronal cell death. Increased internalization of inflammation-driving TLR4 after preconditioning leaves less receptor molecules on the cell surface, providing a probable explanation for significantly reduced microglia activation. Our findings support microglia-focused treatment strategies to overcome secondary brain injury after SAH. Delayed inflammation onset provides a valuable clinical window of opportunity.

scholarly journals Metal Chelating, Inhibitory DNA Damage, and Anti-Inflammatory Activities of Phenolics from Rambutan (Nephelium lappaceum) Peel and the Quantifications of Geraniin and Corilagin

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2263 ◽  
Author(s):  
Yujing Li ◽  
Zhaojie Li ◽  
Hu Hou ◽  
Yongliang Zhuang ◽  
Liping Sun
Keyword(s):  
Dna Damage ◽  
Cell Model ◽  
Biological Properties ◽  
Raw 264.7 Cells ◽  
Raw 264.7 ◽  
Dependent Manner ◽  
Protective Effects ◽  
Metal Chelating ◽  
Study Results ◽  
Anti Inflammatory

Whereas the preparation and biological properties of rambutan peel phenolics (RPP) were explored in our previous studies, the metal chelating, inhibitory DNA damage, and anti-inflammatory activities of RPP were evaluated and the important phenolics of RPP quantified in this study. Results showed that RPP had high Fe2+ and Cu2+-chelating activities with EC50 of 0.80 mg/mL and 0.13 mg/mL, respectively. RPP effectively decreased the production of hydroxyl radical with IC50 of 62.4 μg/mL. The protective effects of RPP against AAPH-induced DNA damage were also explored. RPP efficiently inhibited peroxyl radical-induced plasmid DNA strand breakage. The anti-inflammatory effects of RPP were determined using a lipopolysaccharide (LPS)-induced RAW 264.7 cell model. RPP significantly inhibited the production of nitric oxide (NO) and controlled the levels of inducible NO synthase mRNA in LPS-induced RAW 264.7 cells. The inhibitory activity increased in a dose-dependent manner. The above bioactivity of RPP was associated with its phenolic content and phenolic profiles. Furthermore, the contents of geraniin and corilagin in RPP were determined by an ultra-high performance liquid chromatography coupled with triple quadruple mass spectrometry (UPLC-QQQ-MS), showing 140.02 and 7.87 mg/g extract dry weight. Thus, RPP has potential applications as a novel nutraceutical and functional food in health promotion.

scholarly journals Anti-Inflammatory Effect of By-Products fromHaliotis discus hannaiin RAW 264.7 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ho-Seok Rho ◽  
Hyang Kim ◽  
Jung-Ae Kim ◽  
Fatih Karadeniz ◽  
Byul-Nim Ahn ◽  
...  
Keyword(s):  
Antimicrobial Agents ◽  
Cell Model ◽  
Raw 264.7 Cells ◽  
No Production ◽  
Raw 264.7 ◽  
Food Ingredient ◽  
Pacific Abalone ◽  
Ability To Act ◽  
Anti Inflammatory ◽  
By Products

Several reports promoted the potential of shellfish due to their ability to act as antioxidant, anti-inflammatory, and antimicrobial agents. Pacific abalone,Haliotis discus hannaiviscera is, reported to possess bioactivities such as antioxidative stress and anti-inflammatory. In this study, anti-inflammatory potential of mucus-secreting glands from shell-shucking waste ofH. discus hannaiwas evaluated using RAW 264.7 mouse macrophage cell model. Results indicated that presence ofH. discus hannaimucosubstance by-products (AM) significantly lowered the nitric oxide (NO) production along the expressional suppression of inflammatory mediators such as cytokines TNF-α, IL-1β, and IL-6 and enzymes iNOS and COX-2. Also, AM was shown to increase expression of anti-inflammatory response mediator HO-1. Presence of AM also scavenged the free radicalsin vitro. In conclusion, by-products ofH. discus hannaiare suggested to possess notable anti-inflammatory potential which promotes the possibility of utilization as functional food ingredient.

scholarly journals Anti-inflammatory and Neuroprotective Effects of Fungal Immunomodulatory Protein Involving Microglial Inhibition

2018 ◽  
Vol 19 (11) ◽  
pp. 3678 ◽  
Author(s):  
Wen-Ying Chen ◽  
Cheng-Yi Chang ◽  
Jian-Ri Li ◽  
Jiaan-Der Wang ◽  
Chih-Cheng Wu ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Tyrosine Phosphatase ◽  
Primary Cultures ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neuroprotective Effects ◽  
Fungal Immunomodulatory Protein ◽  
Immunomodulatory Protein ◽  
Anti Inflammatory

Microglia polarization of classical activation state is crucial to the induction of neuroinflammation, and has been implicated in the pathogenesis of numerous neurodegenerative diseases. Fungal immunomodulatory proteins are emerging health-promoting natural substances with multiple pharmacological activities, including immunomodulation. Herein, we investigated the anti-inflammatory and neuroprotective potential of fungal immunomodulatory protein extracted from Ganoderma microsporum (GMI) in an in vitro rodent model of primary cultures. Using primary neuron/glia cultures consisting of neurons, astrocytes, and microglia, a GMI showed an alleviating effect on lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced inflammatory mediator production and neuronal cell death. The events of neuroprotection caused by GMI were accompanied by the suppression of Nitric Oxide (NO), Tumor Necrosis Factor-α (TNF-α), Interleukin-1β (IL-1β), and Prostaglandin E2 (PGE2) production, along with the inhibition of microglia activation. Mechanistic studies showed that the suppression of microglia pro-inflammatory polarization by GMI was accompanied by the resolution of oxidative stress, the preservation of protein tyrosine phosphatase and serine/threonine phosphatase activity, and the reduction of NF-κB, AP-1, cyclic AMP response element-binding protein (CREB), along with signal transducers and activators of transcription (Stat1) transcriptional activities and associated upstream activators. These findings suggest that GMI may have considerable potential towards the treatment of neuroinflammation-mediated neurodegenerative diseases.

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