Attenuation of inflammatory-mediated neurotoxicity by Saururus chinensis extract in LPS-induced BV-2 microglia cells via regulation of NF-κB signaling and anti-oxidant properties
TL;DR: The results indicated that SC inhibited the LPS-stimulated neuroinflammatory responses in BV-2 microglia via regulation of NF-κB signaling and can be potentially used in treating inflammatory-mediated neurodegenerative diseases.
Abstract: A Saururus chinensis Baill (SC) has been used by Native Americans, early colonists and practitioners of Korean traditional medicine for treating several diseases including cancer, rheumatoid arthritis and edema. The objective of this study was to evaluate the effects of SC extract in lipopolysaccharide (LPS)-stimulated neuroinflammatory responses in BV-2 microglial cells. The effects of SC on the LPS–induced neuroinflammatory responses in BV-2 microglial cells were assessed by Western blotting, RT-PCR and immunofluorescence labeling techniques. DPPH and alkyl radical scavenging assay was performed to evaluate the anti-oxidant effects. Comparisons between groups were analyzed using one-way analysis of variance followed by Dunnett’s multiple comparisons test using GraphPad Prism V5.01 software. Pre-treatment with SC extract (1, 5 and 10 μg/mL) significantly (p < 0.001 at 10 μg/mL) and concentration dependently inhibited LPS-induced production of nitric oxide (NO), inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2) and suppressed the inflammatory cytokine levels such as tumor necrosis factor-alpha and interleukin (IL)-6 in BV-2 microglial cells (p < 0.001 at 10 μg/mL). Further, SC suppressed the nuclear factor-kappa B (NF-κB) activation by blocking the degradation of IκB-α. SC also exhibited profound anti-oxidant effects by scavenging 1, 1-diphenyl-2-picrylhydrazyl (DPPH) (IC50: 0.055 mg/mL) and alkyl radicals (IC50: 0.349 mg/mL). High performance liquid chromatography finger printing analysis of SC revealed quercetin (QCT) as one of the major constituents compared with reference standard. QCT also inhibited the excessive release of NO, and inhibited the increased expressional levels of IL-6, iNOS and COX-2 in LPS-stimulated BV-2 cells. Our results indicated that SC inhibited the LPS-stimulated neuroinflammatory responses in BV-2 microglia via regulation of NF-κB signaling. The antioxidant active constituents of SC might be partly involved in delivering such effects. Based on the traditional claims and our present results SC can be potentially used in treating inflammatory-mediated neurodegenerative diseases.
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30 Dec 2019
TL;DR: A synopsis of the recent literature exploring the relationship between quercetin and cognitive performance in Alzheimer’s disease and its potential as a lead compound in clinical applications is provided.
Abstract: Quercetin is a flavonoid with notable pharmacological effects and promising therapeutic potential. It is widely distributed among plants and found commonly in daily diets predominantly in fruits and vegetables. Neuroprotection by quercetin has been reported in several in vitro studies. It has been shown to protect neurons from oxidative damage while reducing lipid peroxidation. In addition to its antioxidant properties, it inhibits the fibril formation of amyloid-β proteins, counteracting cell lyses and inflammatory cascade pathways. In this review, we provide a synopsis of the recent literature exploring the relationship between quercetin and cognitive performance in Alzheimer’s disease and its potential as a lead compound in clinical applications.
204 citations
TL;DR: In this article, the essential role of miR-Let-7a in inflammatory stress by over-expressing it to investigate its role in determining the BV2 microglial phenotype.
59 citations
TL;DR: The results indicated that the BDNF-EPO-Shh novel-signaling pathway underlies the regulation of inflammatory responses and may be regarded as a potential therapeutic target in neurodegenerative diseases.
Abstract: Inhibition of microglial over-activation is an important strategy to counter balance neurodegenerative progression. We previously demonstrated that the adenosine monophosphate-activated protein kinase (AMPK) may be a therapeutic target in mediating anti-neuroinflammatory responses in microglia. Brain-derived neurotrophic factor (BDNF) is one of the major neurotrophic factors produced by astrocytes to maintain the development and survival of neurons in the brain, and have recently been shown to modulate homeostasis of neuroinflammation. Therefore, the present study focused on BDNF-mediated neuroinflammatory responses and may provide an endogenous regulation of neuroinflammation. Among the tested neuroinflammation, epigallocatechin gallate (EGCG) and minocycline exerted BDNF upregulation to inhibit COX-2 and proinflammatory mediator expressions. Furthermore, both EGCG and minocycline upregulated BDNF expression in microglia through AMPK signaling. In addition, minocycline and EGCG also increased expressions of erythropoietin (EPO) and sonic hedgehog (Shh). In the endogenous modulation of neuroinflammation, astrocyte-conditioned medium (AgCM) also decreased the expression of COX-2 and upregulated BDNF expression in microglia. The anti-inflammatory effects of BDNF were mediated through EPO/Shh in microglia. Our results indicated that the BDNF-EPO-Shh novel-signaling pathway underlies the regulation of inflammatory responses and may be regarded as a potential therapeutic target in neurodegenerative diseases. This study also reveals a better understanding of an endogenous crosstalk between astrocytes and microglia to regulate anti-inflammatory actions, which could provide a novel strategy for the treatment of neuroinflammation and neurodegenerative diseases.
48 citations
Cites background from "Attenuation of inflammatory-mediate..."
...Numerous reports demonstrated that microglia are sensitive to the external environmental stimulation and could directly response to pathogenic stimuli by increasing the expression of innate inflammatory mediators [73]....
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TL;DR: In this paper, the authors discuss the potential mechanisms involved in age-related cognitive decline or early stage cognitive impairment and current evidence from clinical human studies conducted on polyphenols and the aforementioned outcomes.
47 citations
TL;DR: In this paper , the authors discuss the potential mechanisms involved in age-related cognitive decline or early stage cognitive impairment and current evidence from clinical human studies conducted on polyphenols and the aforementioned outcomes.
45 citations
References
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TL;DR: A new automated system for the analysis of nitrate via reduction with a high-pressure cadmium column that automatically eliminates interference from other compounds normally present in urine and other biological fluids is described.
11,238 citations
"Attenuation of inflammatory-mediate..." refers methods in this paper
...NO production was assayed by measuring the levels of nitrite in culture medium using a colorimetric assay with Griess reagent [17]....
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TL;DR: Recent progress has been made in understanding the details of the signaling pathways that regulate NF-kappaB activity, particularly those responding to the proinflammatory cytokines tumor necrosis factor-alpha and interleukin-1.
Abstract: NF-κB (nuclear factor-κB) is a collective name for inducible dimeric transcription factors composed of members of the Rel family of DNA-binding proteins that recognize a common sequence motif. NF-κ...
4,724 citations
"Attenuation of inflammatory-mediate..." refers background in this paper
...The molecular mechanisms of NF-κB activation have been well studied, and they involve activation of a cascade of cytoplasmic proteins and nuclear translocation of the NF-κB p65 subunit [42,43]....
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TL;DR: The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes in suppressing toxic/septic shock, graft-vs-host reactions, acute inflammatory reactions, severe phase response, and radiation damage.
Abstract: NF-kappa B is a ubiquitous transcription factor. Nevertheless, its properties seem to be most extensively exploited in cells of the immune system. Among these properties are NF-kappa B's rapid posttranslational activation in response to many pathogenic signals, its direct participation in cytoplasmic/nuclear signaling, and its potency to activate transcription of a great variety of genes encoding immunologically relevant proteins. In vertebrates, five distinct DNA binding subunits are currently known which might extensively heterodimerize, thereby forming complexes with distinct transcriptional activity, DNA sequence specificity, and cell type- and cell stage-specific distribution. The activity of DNA binding NF-kappa B dimers is tightly controlled by accessory proteins called I kappa B subunits of which there are also five different species currently known in vertebrates. I kappa B proteins inhibit DNA binding and prevent nuclear uptake of NF-kappa B complexes. An exception is the Bcl-3 protein which in addition can function as a transcription activating subunit in th nucleus. Other I kappa B proteins are rather involved in terminating NF-kappa B's activity in the nucleus. The intracellular events that lead to the inactivation of I kappa B, i.e. the activation of NF-kappa B, are complex. They involve phosphorylation and proteolytic reactions and seem to be controlled by the cells' redox status. Interference with the activation or activity of NF-kappa B may be beneficial in suppressing toxic/septic shock, graft-vs-host reactions, acute inflammatory reactions, acute phase response, and radiation damage. The inhibition of NF-kappa B activation by antioxidants and specific protease inhibitors may provide a pharmacological basis for interfering with these acute processes.
4,708 citations
"Attenuation of inflammatory-mediate..." refers background in this paper
...Abbreviations BSA: Bovine Serum Albumin; COX-2: Cyclooxygenase-2; DMEM: Dimethyl Sulfoxide; FBS: Fetal Bovine Serum; GAPDH: Glyceraldehydes-3-Phosphate Dehydrogenase; HPLC: High-performance liquid chromatography; IĸB-α: Inhibitory protein kappa B alpha; IL-1β: Interleukin-1beta; IL-6: Interleukin-6; iNOS: Inducible Nitric Oxide Synthase; LPS: Lipopolysaccharide; MTT: p-nitrophenyl phosphate, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; NF-ĸB: Nuclear factor kappa B; NO: Nitric Oxide; PBS: Phosphate-buffered saline; PD: Parkinson’s Disease; RT-PCR: Reverse transcription polymerase chain reaction; SDS: Sodium Dodecyl Sulfate; TNF-α: Tumor necrosis factor-α....
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...Proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 are stimulators and/or co-stimulators of iNOS gene expression and play major roles in inflammatory disease ed BV-2 microglia....
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...We found that SC extract attenuated LPS-induced IκB-α degradation as well as nuclear translocation of p65 in BV-2 microglia, indicating that SC extract inhibits iNOS and TNF-α gene expression in microglia and may be involved in the inhibition of NF-κB activation as a possible mechanism....
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...Pretreatment with SC for 1 h attenuated the upregulation of TNF-α and IL-6 in a concentration-dependent manner (Figure 3A and Figure 3B)....
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...Lee AK, Sung SH, Kim YC, Kim SG: Inhibition of lipopolysaccharide-inducible nitric oxide synthase, TNF-alpha and COX-2 expression by sauchinone effects on I-kappaBalpha phosphorylation, C/EBP and AP-1 activation....
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2,141 citations
"Attenuation of inflammatory-mediate..." refers background in this paper
...A previous study reported that LPS increases activation of the NF-κB subunit (via phosphorylation, ubiquitination, degradation and translocation of p65 and IκB-a) and regulates the expression of iNOS, COX-2, and other pro-inflammatory cytokines [22,23]....
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TL;DR: The role of microglia in three diseases in which their activity is at least partially deleterious: HIV, multiple sclerosis, and Alzheimer's disease is discussed in this article, where the authors discuss their role in protecting the central nervous system.
Abstract: ▪ Abstract Microglia are the principal immune cells in the central nervous system (CNS) and have a critical role in host defense against invading microorganisms and neoplastic cells. However, as with immune cells in other organs, microglia may play a dual role, amplifying the effects of inflammation and mediating cellular degeneration as well as protecting the CNS. In entities like human immunodeficiency virus (HIV) infection of the nervous system, microglia are also critical to viral persistence. In this review we discuss the role of microglia in three diseases in which their activity is at least partially deleterious: HIV, multiple sclerosis, and Alzheimer's disease.
993 citations