Evaluating nitric oxide produced by rat inflamed microglial cell Lline, CHME-5, under the effect of IMOD

Nitric oxide (NO), as a free radical, is produced by inflamed microglia cells and is one of the destructive factors of the immune system and a factor in myelin degradation. Therefore, inhibition of microglia activity is a chief strategy in reducing neurotoxic damage to the central nervous system. In this study, an herbal Immunomodulatory Drug (IMOD) was used to evaluate the effects of this drug in controlling the amount of nitric oxide. Nitric oxide induction was performed by bacterial lipopolysaccharide (LPS) in rat inflamed microglial cell line, CHME-5. ELISA test was used to measure the produced nitric oxide at 24, 48, and 72 hours. The results showed that the high concentrations of IMOD (1.2, and 4% V/V) had anti-inflammatory effects on microglial cells and were able to reduce the amount of nitric oxide in these cells but the effective dose of IMOD was in the range of 1.2% V/V. Therefore, the safest dose and the best time for the effect of IMOD on inflammatory cell groups are 1.2% V/V and 72h, respectively. Hence, with further studies, IMOD can be considered as an herbal anti-inflammatory drug that is effective in controlling neurodegenerative diseases.

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Carbon Monoxide-Neuroglobin Axis Targeting Metabolism Against Neuroinflammation

10.21203/rs.3.rs-852619/v1 ◽

2021 ◽

Author(s):

Daniela Dias-Pedroso ◽

José S. Ramalho ◽

Vilma A. Sardão ◽

John G. Jones ◽

Carlos C. Romão ◽

...

Keyword(s):

Nitric Oxide ◽

Carbon Monoxide ◽

Oxygen Consumption ◽

Inflammatory Response ◽

Microglial Cell ◽

Cell Metabolism ◽

Competent Cell ◽

Metabolic Shift ◽

Anti Inflammatory ◽

Inflammatory Effect

Abstract Microglia are the immune competent cell of the central nervous system (CNS), promoting brain homeostasis and regulating inflammatory response against infection and injury. Chronic or exacerbated neuroinflammation is a cause of damage in several brain pathologies. Endogenous carbon monoxide (CO), produced from the degradation of heme, is described as anti-apoptotic and anti-inflammatory in several contexts, including in the CNS. Neuroglobin (Ngb) is a haemoglobin-homologous protein, which upregulation triggers antioxidant defence and prevents neuronal apoptosis. Thus, we hypothesized a crosstalk between CO and Ngb, in particular, that the anti-neuroinflammatory role of CO in microglia depends on Ngb. A novel CO-releasing molecule (ALF826) based on molybdenum was used for delivering CO in microglial culture.BV-2 mouse microglial cell line was challenged with lipopolysaccharide (LPS) for triggering inflammation, and after 6h ALF826 was added. CO exposure limited inflammation by decreasing inducible nitric oxide synthase (iNOS) expression and the production of nitric oxide (NO) and tumour necrosis factor-a (TNF-a), and by increasing interleukine-10 (IL-10) release. CO-induced Ngb upregulation correlated in time with CO’s anti-inflammatory effect. Moreover, knocking down Ngb reversed the anti-inflammatory effect of CO, suggesting that dependents on Ngb expression. CO-induced Ngb upregulation was independent on ROS signalling, but partially dependent on the transcriptional factor SP1. Finally, microglial cell metabolism is also involved in the inflammatory response. In fact, LPS treatment decreased oxygen consumption in microglia, indicating a switch to glycolysis, which is associated with a proinflammatory. While CO treatment increased oxygen consumption, reverting LPS effect and indicating a metabolic shift into a more oxidative metabolism. Moreover, in the absence of Ngb this phenotype was no longer observed, indicating Ngb is needed for CO’s modulation of microglial metabolism. Finally, the metabolic shift induced by CO did not depend on alteration of mitochondrial population. In conclusion, neuroglobin emerges for the first time as a key player for CO signalling against exacerbated neuroinflammation in microglia.

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Role of nitric oxide and melanogenesis in the accomplishment of anticryptococcal activity by the BV-2 microglial cell line

Journal of Neuroimmunology ◽

10.1016/0165-5728(95)00016-u ◽

1995 ◽

Vol 58 (1) ◽

pp. 111-116 ◽

Cited By ~ 50

Author(s):

E Blasi

Keyword(s):

Nitric Oxide ◽

Cell Line ◽

Microglial Cell ◽

Microglial Cell Line ◽

Anticryptococcal Activity

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Anti-Inflammatory Effects of Modified Buyang Huanwu Decoction

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/6458460 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 2

Author(s):

Hyang-Hwa Ryu ◽

Jun-Chul Kang ◽

Uk Namgung ◽

Song-Yi Kim ◽

Ji-Yeun Park

Keyword(s):

Nitric Oxide ◽

Therapeutic Effects ◽

Buyang Huanwu Decoction ◽

P38 Inhibitor ◽

Length Of Treatment ◽

Proinflammatory Mediators ◽

Inflammatory Status ◽

Medicine Prescription ◽

Anti Inflammatory ◽

High Concentrations

Background/Aims. Buyang Huanwu decoction (BHD) is a traditional Chinese and Korean herbal medicine prescription that has been widely used to treat various diseases including cerebral ischemia, gynecological disease, and neurological disorders. BHD is commonly used as a variable modified combination for synergistic therapeutic effects. However, the mechanism by which modified BHD (mBHD) produces anti-inflammatory effects has not been elucidated yet. The purpose of this study was to develop mBHD with diminished potential side effects and verify its anti-inflammatory effects. Methods. A cytotoxicity assay for BHD was performed using the MTT assay. Following treatment with BHD, mBHD-1, and mBHD-2 in the presence of lipopolysaccharide (LPS), nitric oxide (NO) secretion was detected in cell supernatants using a NO detection kit. The expression of proinflammatory mediators was detected using RT-PCR and western blotting. To verify the mechanism of mBHD, specific inhibitors of JNK (SP600125) or p38 (SB203580) were used for co-treatment with mBHD, and then the changes in NO and nitric oxide synthase (iNOS) were measured. Results. Both mBHD-1 and mBHD-2 showed greater anti-inflammatory effects than BHD. Both mBHD-1 and mBHD-2 inhibited NO secretion and decreased the expression of IL-1β, IL-6, TNF-α, and iNOS. Treatment with a p38 inhibitor and a JNK inhibitor in mBHD-1- and mBHD-2-treated cells resulted in inhibition of NO and iNOS. Conclusion. We provided the first experimental evidence that mBHD may be a more useful anti-inflammatory than BHD. High concentrations or long-term use of BHD may be harmful to inflammatory status. Therefore, the length of treatment and concentration should be considered depending on the targeted disease.

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Nitric oxide/cyclic GMP signaling regulates motility of a microglial cell line and primary microglia in vitro

Brain Research ◽

10.1016/j.brainres.2014.03.048 ◽

2014 ◽

Vol 1564 ◽

pp. 9-21 ◽

Cited By ~ 17

Author(s):

Hannah Scheiblich ◽

Frank Roloff ◽

Vikramjeet Singh ◽

Martin Stangel ◽

Michael Stern ◽

...

Keyword(s):

Nitric Oxide ◽

Cell Line ◽

Cyclic Gmp ◽

Microglial Cell ◽

Primary Microglia ◽

Microglial Cell Line

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Design, synthesis, and anti-neuroinflammatory activity of amidecontaining dithiolethiones

Medicinal Chemistry ◽

10.2174/1573406416666200909105100 ◽

2020 ◽

Vol 16 ◽

Author(s):

Karrington Craig ◽

Paula Avila ◽

Dennis A. Brown

Keyword(s):

Cell Line ◽

Microglial Cell ◽

Neuronal Cell ◽

Activity Data ◽

Design Synthesis ◽

Inflammatory Damage ◽

Immune Mediated ◽

Microglial Cell Line ◽

The Central Nervous System ◽

Anti Oxidant

Background: Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterized by demyelination of neurons and neurodegeneration. Current MS therapies ameliorate inflammatory damage but are unable to address the degenerative aspects of the disease. Objective: In this report, we evaluate the ability of amide-based dithiolethiones (DTTs) to suppress neuroinflammation in microglia and increase anti-oxidant capacity neuron-like cells. Methods: A series of amide-containing DTTs were designed, synthesized, and assayed for ability to suppress proneuroinflammatory cytokines IL-12p40 and IL-23p19 induced by LPS in the BV2 microglial cell line. Lead analog 2c was identified and further characterized. Results: Structure-activity data revealed tolerance towards a variety of amides. Morpholine analog 2c dose-dependently reduced various other inflammatory cytokines and mediators, including TNF, IL-6, IL-1β, NOS2, and COX2. Additionally, 2c elevated cellular levels of glutathione in SH-SH5Y neuronal cell line. Furthermore, mechanistic studies showed 2c increased the expression of anti-inflammatory Nrf2 and HMOX proteins. Conclusion: The combination of anti-neuroinflammatory and anti-oxidant activities of amide-based DTTs suggest they are promising agents for the treatment of both demyelination and neurodegeneration in MS.

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Vitamin D3 inhibits proinflammatory cytokines and nitric oxide production by the EOC13 microglial cell line

Journal of Neuroscience Research ◽

10.1002/jnr.10491 ◽

2003 ◽

Vol 71 (4) ◽

pp. 575-582 ◽

Cited By ~ 72

Author(s):

Christian Lefebvre d'Hellencourt ◽

Claudia N. Montero-Menei ◽

Rozenn Bernard ◽

Dominique Couez

Keyword(s):

Nitric Oxide ◽

Cell Line ◽

Proinflammatory Cytokines ◽

Vitamin D3 ◽

Microglial Cell ◽

Nitric Oxide Production ◽

Oxide Production ◽

Microglial Cell Line

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Heme Oxygenase-1-Inducing Activity of 4-Methoxydalbergione and 4’-Hydroxy-4-methoxydalbergione from Dalbergia odorifera and Their Anti-inflammatory and Cytoprotective Effects in Murine Hippocampal and BV2 Microglial Cell Line and Primary Rat Microglial Cells

Neurotoxicity Research ◽

10.1007/s12640-017-9796-8 ◽

2017 ◽

Vol 33 (2) ◽

pp. 337-352 ◽

Cited By ~ 5

Author(s):

Dong-Cheol Kim ◽

Dong-Sung Lee ◽

Wonmin Ko ◽

Kwan-Woo Kim ◽

Hye Jin Kim ◽

...

Keyword(s):

Cell Line ◽

Heme Oxygenase ◽

Microglial Cell ◽

Microglial Cells ◽

Heme Oxygenase 1 ◽

Microglial Cell Line ◽

Anti Inflammatory ◽

Dalbergia Odorifera

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Acanthamoeba culbertsoni Elicits Soluble Factors That Exert Anti-Microglial Cell Activity

Infection and Immunity ◽

10.1128/iai.00047-10 ◽

2010 ◽

Vol 78 (9) ◽

pp. 4001-4011 ◽

Cited By ~ 11

Author(s):

Jenica L. Harrison ◽

Gabriela A. Ferreira ◽

Erinn S. Raborn ◽

Audrey D. Lafrenaye ◽

Francine Marciano-Cabral ◽

...

Keyword(s):

Microglial Cell ◽

Cell Activity ◽

Opportunistic Pathogen ◽

Neonatal Rat ◽

Cell Contact ◽

Soluble Factors ◽

Microglial Cell Line ◽

The Central Nervous System ◽

Acanthamoeba Culbertsoni ◽

Induced Apoptosis

ABSTRACT Acanthamoeba culbertsoni is an opportunistic pathogen that causes granulomatous amoebic encephalitis (GAE), a chronic and often fatal disease of the central nervous system (CNS). A hallmark of GAE is the formation of granulomas around the amoebae. These cellular aggregates consist of microglia, macrophages, lymphocytes, and neutrophils, which produce a myriad of proinflammatory soluble factors. In the present study, it is demonstrated that A. culbertsoni secretes serine peptidases that degrade chemokines and cytokines produced by a mouse microglial cell line (BV-2 cells). Furthermore, soluble factors present in cocultures of A. culbertsoni and BV-2 cells, as well as in cocultures of A. culbertsoni and primary neonatal rat cerebral cortex microglia, induced apoptosis of these macrophage-like cells. Collectively, the results indicate that A. culbertsoni can apply a multiplicity of cell contact-independent modes to target macrophage-like cells that exert antiamoeba activities in the CNS.

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