Discovery of Active Ingredients Targeted TREM2 by SPR Biosensor-UPLC/MS Recognition System, and Investigating the Mechanism of Anti-Neuroinflammatory Activity on the Lignin-Amides from Datura metel Seeds

As a new target protein for Alzheimer’s disease (AD), the triggering receptor expressed on myeloid Cells 2 (TREM2) was expressed on the surface of microglia, which was shown to regulate neuroinflammation, be associated with a variety of neuropathologic, and regarded as a potential indicator for monitoring AD. In this study, a novel recognition system based on surface plasmon resonance (SPR) for the TREM2 target spot was established coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-MS), in order to screen the active ingredients targeting TREM2 from Datura metel seeds. The results showed that four lignan-amides were discovered as candidate compounds by SPR biosensor-UPLC/MS recognition analysis. According to the guidance of the active ingredients discovered by the system, the lignin-amides from Datura metel seeds (LDS) were preliminarily identified as containing 27 lignan-amides, which were enriched compositions by the HP-20 of Datura metel seeds. Meanwhile, the anti-inflammatory activity of LDS was evaluated in BV2 microglia induced by LPS. Our experimental results demonstrated that LDS could reduce NO release in LPS-treated BV2 microglia cells and significantly reduce the expression of the proteins of inducible Nitric Oxide Synthase (iNOS), cyclooxygenase 2 (COX-2), microtubule-associated protein tau (Tau), and ionized calcium-binding adapter molecule 1 (IBA-1). Accordingly, LDS might increase the expression of TREM2/DNAX-activating protein of 12 kDa (DAP12) and suppress the Toll-like receptor SX4 (TLR4) pathway and Recombinant NLR Family, Pyrin Domain Containing Protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1 (Caspase-1) inflammasome expression by LDS in LPS-induced BV2 microglial cells. Then, the inhibitory release of inflammatory factors Interleukin 1 beta (IL-1β), Interleukin 6 (IL-6), and Tumor necrosis factor-alpha (TNFα) inflammatory cytokines were detected to inhibit neuroinflammatory responses. The present results propose that LDS has potential as an anti-neuroinflammatory agent against microglia-mediated neuroinflammatory disorders.

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A Randomized Control Trial Study to Determine the Effect of Melatonin on Serum Levels of IL-1β and TNF-α in Patients with Multiple Sclerosis

Iranian Journal of Allergy Asthma and Immunology ◽

10.18502/ijaai.v18i6.2177 ◽

2020 ◽

Cited By ~ 1

Author(s):

Masoomeh Yosefifard ◽

Gholamhassan Vaezi ◽

Ali Akbar Malekirad ◽

Fardin Faraji ◽

Vida Hojati

Keyword(s):

Multiple Sclerosis ◽

Interleukin 1 ◽

Serum Levels ◽

Inflammatory Factors ◽

Control Group ◽

Necrosis Factor Alpha ◽

Treatment Groups ◽

Tnf Α ◽

Significant Difference ◽

The Central Nervous System

Multiple sclerosis (MS) is the most common neurological disease that happens at a young age. MS is an inflammatory disease; associated with the demyelination of the central nervous system. Therefore, some inflammatory factors are effective in the mechanism and progression of the disease. Melatonin, as a multi-effect substance including anti-inflammatory effects, can reduce symptoms of MS in patients with a change in their inflammatory factors level. In this study, 50 MS patients who were referred to the MS Society of Markazi Province were randomly selected. All patients were treated with routine MS treatment (interferon) and were divided into control (25 placebo recipients) and treatment (25 recipients of 3 mg melatonin per day for 24 weeks) groups. Anthropometric data of patients including height, weight, and age were determined. Blood samples were collected after fasting in order to determine serum levels of interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Then, samples were immediately centrifuged for serum separation and sera were transferred to a freezer at -80°C and serum levels of these factors were determined; using ELISA kit. The results of this study showed that there was no significant difference between the control and treatment groups in terms of serum levels of TNF-α. However, the level of IL-1β was significantly reduced in the treatment group compared to the control group, indicating that melatonin decreases this inflammatory substance. Our findings suggest a valuable strategy in the treatment of patients who suffer from MS

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In Vitro Anti-Inflammatory Effects of Phenolic Compounds from Moraiolo Virgin Olive Oil (MVOO) in Brain Cells via Regulating the TLR4/NLRP3 Axis

Molecules ◽

10.3390/molecules24244523 ◽

2019 ◽

Vol 24 (24) ◽

pp. 4523 ◽

Cited By ~ 2

Author(s):

Agnese Taticchi ◽

Stefania Urbani ◽

Elisabetta Albi ◽

Maurizio Servili ◽

Michela Codini ◽

...

Keyword(s):

Olive Oil ◽

Calcium Binding ◽

Virgin Olive Oil ◽

Brain Cells ◽

Cns Injury ◽

Microglia Cell ◽

Pyrin Domain ◽

Bv2 Microglia ◽

Anti Inflammatory

Neuroinflammation is a feature of many classic neurodegenerative diseases. In the healthy brain, microglia cells are distributed throughout the brain and are constantly surveilling the central nervous system (CNS). In response to CNS injury, microglia quickly react by secreting a wide array of apoptotic molecules. Virgin olive oil (VOO) is universally recognized as a symbol of the Mediterranean diet. In the current study, using lipopolysaccharide (LPS)-stimulated BV2 microglia, the anti-inflammatory effects of VOO phenolic extracts from Moraiolo cultivar (MVOO-PE) were investigated. The results showed that low concentration of MVOO-PE prevented microglia cell death and attenuated the LPS-induced activation of toll-like receptor 4 (TLR4)/NOD-like receptor pyrin domain-containing-3 (NLRP3) signaling cascade. The levels of TLR4 and NF-kB were diminished, as well as NLRP3 inflammasome and interleukin-1β (IL-1β) production. Cyclooxygenase-2 (COX-2) isoenzyme and ionized calcium binding adaptor molecule 1 (Iba-1) inflammatory mediator were also reduced. By modulating the TLR4/NLRP3 axis, MVOO-PE pretreatment was able to significantly down-regulate the mRNA expression of inflammatory mediators and suppress the cytokine secretion. Finally, we showed protective effect of MVOO-PE in a transwell neuron–microglia co-culture system. In conclusion, these results suggest that MVOO-PE could exerts anti-inflammatory activity on brain cells and become a promising candidate for preventing several neuroinflammatory diseases.

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The Effect of Scaling and Root Planning on Salivary TNF-α and IL-1α Concentrations in Patients with Chronic Periodontitis

The Open Dentistry Journal ◽

10.2174/1874210601711010573 ◽

2017 ◽

Vol 11 (1) ◽

pp. 573-580 ◽

Cited By ~ 7

Author(s):

Masoome Eivazi ◽

Negar Falahi ◽

Nastaran Eivazi ◽

Mohammad Ali Eivazi ◽

Asad Vaisi Raygani ◽

...

Keyword(s):

Chronic Periodontitis ◽

Interleukin 1 ◽

Negative Relationship ◽

Inflammatory Factors ◽

Control Group ◽

Pocket Depth ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Root Planning ◽

Scaling And Root Planning

Objective:Periodontitis is one of the main diseases in the oral cavity that causes tooth loss. The host immune response and inflammatory factors have important role in periodontal tissue. The current study was done with the objective to determine the effect of scaling and root planning on the salivary concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin-1-alpha (IL-1α).Methods:In this quasi-experimental clinical trial, 29 patients with chronic periodontitis and 29 healthy subjects without periodontitis were studied. Clinical examination findings and salivary TNF-α and IL-1α (using ELISA method) were compared before and after scaling, root planning.Results:Before starting treatment, salivary TNF-α and IL-1α concentrations were higher in healthy control group than in periodontitis group (P< 0.05). Non-surgical treatment increased the concentration of these two biomarkers in the saliva. However, increase in IL-1α concentration was not statistically significant (P= 0.056). There was a negative relationship between TNF-α and IL-1α levels with pocket depth and attachment loss (P< 0.05).Conclusion:Scaling and root planning improved periodontal disease indices and salivary TNF-α and IL-1α levels.

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Exogenous hydrogen sulfide alleviates surgery-induced neuroinflammatory cognitive impairment in adult mice by inhibiting NO signaling

BMC Anesthesiology ◽

10.1186/s12871-019-0927-z ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 2

Author(s):

Lijun Yin ◽

Shunli Gao ◽

Changkun Li

Keyword(s):

Nitric Oxide ◽

Hydrogen Sulfide ◽

Cognitive Dysfunction ◽

Calcium Binding ◽

Interleukin 1 ◽

Terminal Deoxynucleotidyl Transferase ◽

Tunel Staining ◽

Necrosis Factor Alpha ◽

Western Blots ◽

No Signaling

Abstract Background To investigate the effect and mechanisms of exogenous hydrogen sulfide in surgery-induced neuroinflammatory cognitive dysfunction. Methods C57BL/6 J male mice (n = 140) were used and randomly divided into seven groups: the sham group, surgery group, GYY4137 group, L-NAME group, surgery+GYY4137 group, surgery +L-NAME group, and surgery+GYY4137 + L-NAME group. After the interventions, open field tests (OFT) and the Morris water maze (MWM) test were conducted to evaluate learning and memory abilities in the mice. ELISAs, nitrate reductase assays, and Western blots (WB) were conducted to evaluate interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), nitric oxide (NO), inducible nitric oxide synthase (iNOS), malondialdehyde (MDA), and antioxidant enzyme superoxide dismutase (SOD) levels. Furthermore, the expression level of microglial marker ionized calcium binding adaptor molecule 1 (IBA) in the hippocampal CA1 and CA3 areas was detected by an immunohistochemical (IHC) assay and apoptotic cells were observed using terminal deoxynucleotidyl transferase dUTP end-labeling (TUNEL) staining kits. Results We found that surgery induced neuroinflammatory cognitive dysfunction, oxidative stress, microglial activation, and cell apoptosis in the hippocampus. Moreover, following surgery, NO and iNOS levels were elevated in the hippocampus. Notably, all the effects caused by surgery were reversed by the H2S donor GYY4137 or the iNOS inhibitor N(gamma)-nitro-L-arginine methyl ester (L-NAME). However, the combined application of GYY4137 and L-NAME was not superior to treatment with either agent alone and the effect of GYY4137 was similar to that of L-NAME. Conclusion The long-acting hydrogen sulfide donor GYY4137 had an ability to reversed the cognitive deficits and inflammation caused by carotid artery exposure surgery. This implies that NO signaling pathways might participate in this process. These results indicate that exogenous H2S may be a promising therapy for POCD.

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Serum Inflammatory Factor Profiles in the Pathogenesis of High-Altitude Polycythemia and Mechanisms of Acclimation to High Altitudes

Mediators of Inflammation ◽

10.1155/2021/8844438 ◽

2021 ◽

Vol 2021 ◽

pp. 1-9

Author(s):

Hai Yi ◽

Qianjin Yu ◽

Dongfeng Zeng ◽

Zhaohua Shen ◽

Jiali Li ◽

...

Keyword(s):

High Altitude ◽

Interleukin 1 ◽

Interleukin 2 ◽

Inflammatory Factors ◽

Tnf Alpha ◽

Antibody Array ◽

Inflammatory Factor ◽

High Altitudes ◽

Serum Samples ◽

Necrosis Factor Alpha

High-altitude polycythemia (HAPC) is a common aspect of chronic mountain sickness (CMS) caused by hypoxia and is the main cause of other symptoms associated with CMS. However, its pathogenesis and the mechanisms of high-altitude acclimation have not been fully elucidated. Exposure to high altitude is associated with elevated inflammatory mediators. In this study, the subjects were recruited and placed into a plain control (PC) group, plateau control (PUC) group, early HAPC (eHAPC) group, or a confirmed HAPC (cHAPC) group. Serum samples were collected, and inflammatory factors were measured by a novel antibody array methodology. The serum levels of interleukin-2 (IL-2), interleukin-3 (IL-3), and macrophage chemoattractant protein-1 (MCP-1) in the eHAPC group and the levels of interleukin-1 beta (IL-1 beta), IL-2, IL-3, tumor necrosis factor-alpha (TNF-alpha), MCP-1, and interleukin-16 (IL-16) in the cHAPC group were higher than those in the PUC group. More interestingly, the expression of IL-1 beta, IL-2, IL-3, TNF-alpha, MCP-1, and IL-16 in the PUC group showed a remarkable lower value than that in the PC group. These results suggest that these six factors might be involved in the pathogenesis of HAPC as well as acclimation to high altitudes. Altered inflammatory factors might be new biomarkers for HAPC and for high-altitude acclimation.

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Multifaceted Protective Role of Glucosamine against Osteoarthritis: Review of Its Molecular Mechanisms

Scientia Pharmaceutica ◽

10.3390/scipharm87040034 ◽

2019 ◽

Vol 87 (4) ◽

pp. 34 ◽

Cited By ~ 2

Author(s):

Al-Saadi ◽

Pang ◽

Ima-Nirwana ◽

Chin

Keyword(s):

Molecular Mechanisms ◽

Interleukin 1 ◽

Cartilage Degeneration ◽

Redox Status ◽

Joint Disease ◽

Inflammatory Factors ◽

Current Evidence ◽

Necrosis Factor Alpha ◽

Joint Health ◽

Anti Inflammatory

Osteoarthritis (OA) is a joint disease resulting from cartilage degeneration and causing joint pain and stiffness. Glucosamine exerts chondroprotective effects and effectively reduces OA pain and stiffness. This review aims to summarise the mechanism of glucosamine in protecting joint health and preventing OA by conducting a literature search on original articles. Current evidence has revealed that glucosamine exhibits anti-inflammatory effects by reducing the levels of pro-inflammatory factors (such as tumour necrosis factor-alpha, interleukin-1, and interleukin-6) and enhancing the synthesis of proteoglycans that retard cartilage degradation and improve joint function. Additionally, glucosamine improves cellular redox status, reduces OA-mediated oxidative damages, scavenges free radicals, upregulates antioxidant proteins and enzyme levels, inhibits the production of reactive oxygen species, and induces autophagy to delay OA pathogenesis. In conclusion, glucosamine prevents OA and maintains joint health by reducing inflammation, improving the redox status, and inducing autophagy in joints. Further studies are warranted to determine the synergistic effect of glucosamine with other anti-inflammatory and/or antioxidative agents on joint health in humans.

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Upregulated TSG-6 Expression in ADSCs Inhibits the BV2 Microglia-Mediated Inflammatory Response

BioMed Research International ◽

10.1155/2018/7239181 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Yang Hu ◽

Gaigai Li ◽

Ye Zhang ◽

Na Liu ◽

Ping Zhang ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Inflammatory Response ◽

Tumor Necrosis ◽

High Throughput Sequencing ◽

Bioinformatics Analysis ◽

Interleukin 1 ◽

Negative Control ◽

Necrosis Factor Alpha ◽

Bv2 Microglia ◽

Necrosis Factor

Objectives. The microglial cells are immune surveillance cells in the central nervous system and can be activated during neurological disorders. Adipose-derived stem cells (ADSCs) were reported to inhibit the inflammatory response in microglia by secreting proteins like tumor necrosis factor-inducible gene 6 protein (TSG-6). We aim to explore the mechanisms and the associated microRNAs. Methods. ADSCs were cultured and TSG-6 expression was evaluated. ADSCs were cocultured with lipopolysaccharide- (LPS-) induced BV2 microglia and the supernatant was harvested for detecting cytokines. The total RNA was extracted and sequenced by high-throughput sequencing. MicroRNA profiles were compared between two treatment groups of ADSCs. A comprehensive bioinformatics analysis and confirmation experiments were performed to identify the microRNAs targeting at TSG-6. Results. We found that ADSCs could secrete TSG-6 to inhibit the proinflammatory cytokines, including interleukin-1 beta and interleukin-6, and tumor necrosis factor alpha (TNFα), produced by LPS-induced microglia-mediated inflammatory response. Bioinformatics analysis showed a total of 35 microRNAs differentially expressed between the two groups of ADSCs, and miR-214-5p was identified as a regulator of TSG-6 mRNA. Conclusion. Following a treatment with TNFα, ADSCs can regulate the inflammatory response in LPS-activated BV2 microglia by upregulating TSG-6 expression, which itself is under the negative control of miR-214-5p.

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Effect of Resveratrol on NF-κB Activity in Rat Peritoneal Macrophages

The American Journal of Chinese Medicine ◽

10.1142/s0192415x06004156 ◽

2006 ◽

Vol 34 (04) ◽

pp. 623-630 ◽

Cited By ~ 14

Author(s):

Zhen-Hua Ma ◽

Qing-Yong Ma ◽

Lian-Cai Wang ◽

Huan-Chen Sha ◽

Sheng-Li Wu ◽

...

Keyword(s):

Culture Medium ◽

Interleukin 1 ◽

Peritoneal Macrophages ◽

Inflammatory Factors ◽

Future Application ◽

Control Group ◽

Sprague Dawley ◽

Necrosis Factor Alpha ◽

Tnf Α ◽

Significant Difference

This study was to investigate the inhibitive effect of resveratrol (RESV) on nuclear factor kappa B (NF-κB) expression and activity induced by lipopolysaccharide (LPS) in rat peritoneal macrophages (PMA). Male Sprague-Dawley (SD) rats were randomly divided into 7 groups, including control group, LPS group and RESV I-V group. In the LPS group, PMA were incubated in DMEM containing LPS (10 μg/ml), whereas in control group, PMA were incubated in DMEM only. In the RESV I-V groups, PMA were incubated in DMEM containing LPS (10 μg/ml) and different concentrations of RESV. After 24 hours of incubation, NF-κB activity in PMA, and the levels of tumor necrosis factor alpha (TNF-α), interleukin-1 (IL-1) and nitric oxide (NO) in the culture medium were measured. In the concentrations of 1.25-5 μg/ml, RESV had a dose- dependent inhibitive effect on NF-κB activity in PMA as well as the expressions of TNF-α, IL-1 and NO in the culture medium contrasted with the LPS group. There was no significant difference in the levels of these pro-inflammatory factors between the groups of 5 μg/ml and 10 μg/ml RESV. In conclusion, RESV has the potential for the future application of preventing inflammatory diseases involving PMA.

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Ruscogenin alleviates cognitive dysfunction by inhibiting the activation of isoflurane-induced NLRP3 inflammasome in aged mice

Quality Assurance and Safety of Crops & Foods ◽

10.15586/qas.v13i3.964 ◽

2021 ◽

Vol 13 (3) ◽

pp. 109-115

Author(s):

Xiaohu Liang ◽

Xiaoqun Luo ◽

Danping Li ◽

Lingqiong Kong

Keyword(s):

Cognitive Dysfunction ◽

Calcium Binding ◽

Neuronal Damage ◽

Postoperative Cognitive Dysfunction ◽

Neuron Specific Enolase ◽

Morris Water Maze Test ◽

Neuroprotective Effects ◽

Necrosis Factor Alpha ◽

Aged Mice ◽

Pyrin Domain

Ruscogenin exerts an anti-inflammatory effect in the pathogenesis of various human diseases, including pulmonary hypertension, acute lung injury, acute pancreatitis and cerebral ischemia. Its role in isoflurane-induced rats with postoperative cognitive dysfunction (POCD) was investigated in this study. Aged rats were exposed to isoflurane for establishing a model of POCD, and administered with ruscogenin by gavage. Cognitive dysfunction was evaluated by the Morris water maze test. Hematoxylin and Eosin (H&E) staining was designed to assess neuronal damage. Markers of brain damage and neuroinflammation were detected by enzyme-linked-immunosorbent serologic assay. Isoflurane exposure caused impaired cognitive function by increasing escape latency, decreasing the time taken for crossing target and time in target quadrant. However, administration of ruscogenin reversed these cognitive dysfunctions. Abnormal morphological phenomena on neurons and enhanced levels of serum calcium-binding protein β (S-100β) and neuron-specific enolase (NSE) were identified in mice post-isoflurane exposure. Administration of ruscogenin ameliorated the neuronal morphological damages and reduced the levels of S-100β and NSE in the hippocampi of isoflurane-induced aged mice. Ruscogenin also attenuated isoflurane-induced enhancements in the levels of Interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha in the hippocampi of mice. Isoflurane-induced enhancements in the mRNA expression levels of NLR family pyrin domain containing 3 (NLRP3), ASC, IL-1β and IL-18 proteins were also restored by administration of ruscogenin. Ruscogenin exerted neuroprotective effects against isoflurane-induced cognitive dysfunction and neuroinflammation through blocking of NLRP3 pathway.

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Upregulation of Connexin-43 is Critical for Irradiation-induced Neuroinflammation

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527317666180706124602 ◽

2018 ◽

Vol 17 (7) ◽

pp. 539-546 ◽

Cited By ~ 1

Author(s):

Wei Chen ◽

Wusong Tong ◽

Yijun Guo ◽

Bin He ◽

Lei Chen ◽

...

Keyword(s):

Ischemic Stroke ◽

Connexin 43 ◽

Interleukin 1 ◽

Pathological Process ◽

Inflammatory Factors ◽

Mrna Levels ◽

Necrosis Factor Alpha ◽

Γ Radiation ◽

Neural Damage ◽

Cx 43

Background: Radiation therapy is widely used for the treatment of pituitary adenomas. Unfortunately, it might raise the risk of ischemic stroke, with neuroinflammation being a major pathological process. Astrocytes are the most abundant cell type in the central nervous system and have been reported for playing important roles in ischemic stroke. Objective: Here we studied how γ-radiation would introduce astrocytes into a detrimental state for neuroinflammation and provide new theory evidence and target for the clinical management of inflammation- related neural damage after radiation-induced ischemic stroke. Method: HA-1800 cells were treated with γ-radiation and then the protein and mRNA levels of Connexin (Cx)-43 were evaluated by western and q-PCR. The culture supernatant was collected and the concentrations of the inflammatory factors were determined by ELISA. MiRNA complementary to Cx-43 was designed through the online tools. Results: Cx-43 is upregulated in the treatment of γ-radiation in astrocytes and γ-radiation introduced the detrimental function of astrocytes: cell viability was reduced while the apoptotic cells were increased. Inflammatory factors like tumor necrosis factor alpha, interferon gamma, interleukin-6, interleukin 1-beta were dramatically up-regulated by the irradiation. MiR-374a rescued irradiation induced Cx-43 up-regulation of astrocytes and eliminated detrimental function triggered by γ-radiation. Conclusion: Cx-43 expression level may play an important role in the inflammation-related neural damage after irradiation-induced ischemic stroke.

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