Chunghyuldan attenuates brain microglial inflammatory response

2009 ◽  
Vol 87 (6) ◽  
pp. 448-454 ◽  
Author(s):  
Kyong Nyon Nam ◽  
Hoon-Ji Jung ◽  
Mi-Hyun Kim ◽  
Chulhun Kang ◽  
Woo-Sang Jung ◽  
...  
Keyword(s):  
Rat Brain ◽  
Microglial Activation ◽  
Inflammatory Responses ◽  
Small Vessel Disease ◽  
Inhibitory Effect ◽  
Stroke Recurrence ◽  
Pcr Analysis ◽  
Prostaglandin E ◽  
Tnf Α ◽  
Proinflammatory Molecules

Microglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory molecules and neurotoxins. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target stroke and neurodegenerative diseases. Chunghyuldan, a combinatorial drug consisting of Scutellariae Radix, Coptidis Rhizoma, Phellodendri Cortex, Gardeniae Fructus, and Rhei Rhizoma, has an inhibitory effect on stroke recurrence in patients with small-vessel disease. It has also been reported to confer antihypertensive, antihyperlipidemic, and antiinflammatory effects. The aim of this study was to examine whether Chunghyuldan suppresses microglial activation. Chunghyuldan was effective at inhibiting LPS-induced nitric oxide (NO) release from rat brain microglia. Real-time reverse transcriptase PCR analysis revealed that pretreatment of rat brain microglia with Chunghyuldan attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-α, interleukin-1β, and cyclooxygenase-2. In rat brain microglia, Chunghyuldan reduced the LPS-stimulated production of TNF-α and prostaglandin E2. In addition, Chunghyuldan significantly decreased LPS-induced phosphorylation of the ERK1/2 and p38 signaling proteins. These results suggest that Chunghyuldan provide neuroprotection by reducing the release of various proinflammatory molecules from activated microglia.

scholarly journals Activated Platelets Induce an Anti-Inflammatory Response of Monocytes/Macrophages through Cross-Regulation of PGE2and Cytokines

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Bona Linke ◽  
Yannick Schreiber ◽  
Bettina Picard-Willems ◽  
Patrick Slattery ◽  
Rolf M. Nüsing ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Innate Immune ◽  
Prostaglandin E ◽  
Murine Bone Marrow ◽  
Activated Platelets ◽  
Monocytes And Macrophages ◽  
Inflammatory Processes ◽  
Necrosis Factor

Platelets are well known for their role in hemostasis and are also increasingly recognized for their roles in the innate immune system during inflammation and their regulation of macrophage activation. Here, we aimed to study the influence of platelets on the production of inflammatory mediators by monocytes and macrophages. Analyzing cocultures of platelets and murine bone marrow-derived macrophages or human monocytes, we found that collagen-activated platelets release high amounts of prostaglandin E2(PGE2) that leads to an increased interleukin- (IL-) 10 release and a decreased tumor necrosis factor (TNF)αsecretion out of the monocytes or macrophages. Platelet PGE2mediated the upregulation of IL-10 in both cell types via the PGE2receptor EP2. Notably, PGE2-mediated IL-10 synthesis was also mediated by EP4 in murine macrophages. Inhibition of TNFαsynthesis via EP2 and EP4, but not EP1, was mediated by IL-10, since blockade of the IL-10 receptor abolished the inhibitory effect of both receptors on TNFαrelease. This platelet-mediated cross-regulation between PGE2and cytokines reveals one mechanism how monocytes and macrophages can attenuate excessive inflammatory responses induced by activated platelets in order to limit inflammatory processes.

scholarly journals Keel Fracture Causes Stress and Inflammatory Responses and Inhibits the Expression of the Orexin System in Laying Hens

Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 804 ◽  
Author(s):  
Haidong Wei ◽  
Chun Li ◽  
Hongwei Xin ◽  
Shuang Li ◽  
Yanju Bi ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Laying Hens ◽  
Inflammatory Responses ◽  
Abdominal Muscle ◽  
Inflammatory Factors ◽  
Prostaglandin E ◽  
Inflammatory Factor ◽  
Tnf Α ◽  
Cox 2 ◽  
The Brain

Keel fracture has negative effects on the health and welfare of laying hens. We investigated effects of keel fracture on stress, inflammation, and the orexin system in laying hens. Ninety 17-week-old Lohmann white laying hens were palpated and euthanatized at 42 weeks old, and marked as normal keel (NK)/fractured keel (FK) from absence/presence of keel fracture. Serum, brain, liver, and abdominal-muscle samples were collected from 10 NK and 10 FK hens to determine the stress and inflammatory responses and the activity of orexin systems by corticosterone content, expression of heat shock proteins (TNF-α 60, 70, 90), and inflammatory factors (tumor necrosis factor (TNF)-α, nuclear factor-kappa Bp65 (NF-κBp65), inducible nitric oxide synthase (iNOS), prostaglandin E synthases (PTGEs), cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β)), orexin (ORX), and orexin-receptor 1/2 (ORXR1/ORXR2). The FK hens had higher serum corticosterone content, Hsps, and inflammatory factor mRNA expression levels than NK hens, although levels of iNOS in the liver and TNF-α in the muscle were similar. Protein levels of Hsp70 and Hsp90 in the brain and liver, iNOS and COX-2 in the liver, NF-κBp65, iNOS, and COX-2 in the brain of FK hens were increased compared with NK hens. Furthermore, FK hens had lower mRNA expression of ORX, ORXR1, and ORXR2 than NK hens. Therefore, keel fracture causes stress and inflammation, and inhibits the expression of the orexin system in laying hens.

Inhibition of TNF-α gene expression and bioactivity by site-specific transcription factor-binding oligonucleotides

2003 ◽  
Vol 284 (2) ◽  
pp. L386-L394 ◽  
Author(s):  
Jianping Ye ◽  
Liying Wang ◽  
Xiaoying Zhang ◽  
Vimon Tantishaiyakul ◽  
Yon Rojanasakul
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Inflammatory Responses ◽  
Inhibitory Effect ◽  
Therapeutic Modality ◽  
Nuclear Factor ◽  
Cellular Delivery ◽  
Factor Binding ◽  
Tnf Α ◽  
Transcriptional Inactivation

The present study investigated transcriptional inactivation of TNF-α gene by nuclear factor-binding oligonucleotides (ON) and their effects on pulmonary inflammatory responses in mice. PCR-based gene mutation and gel shift assays were used to identify specific cis-acting elements necessary for nuclear factor binding and transactivation of TNF-α gene by lipopolysaccharide (LPS). LPS inducibility of TNF-α was shown to require transcriptional activation by NF-κB at multiple binding sites, including the −850 (κ1), −655 (κ2), and −510 (κ3) sites, whereas the −210 (κ4) site had no effect. Maximum inducibility was associated with the activation of κ3 site. The sequence-specific, double-stranded ON targeting this site was most effective in inhibiting TNF-α activity induced by LPS. The inhibitory effect of ON on TNF-α bioactivity was also investigated using a murine lung inflammation model. Pretreatment of mice with ON, but not its mutated sequence, inhibited LPS-induced inflammatory neutrophil influx and TNF-α production by lung cells. Effective inhibition by ON in this model was shown to require a liposomal agent for efficient cellular delivery of the ON. Together, our results indicate that transcriptional inactivation of TNF-α gene can be achieved by using ON that compete for nuclear factor binding to TNF-α gene promoter. This gene inhibition approach may be used as a research tool or as potential therapeutic modality for diseases with etiology dependent on aberrant gene expression.

scholarly journals Neutrophil recruitment inhibitory factor: a possible candidate for a novel cytokine

1992 ◽  
Vol 1 (1) ◽  
pp. 49-54 ◽  
Author(s):  
W. M. S. C. Tamashiro ◽  
B. M. Tavares-Murta ◽  
F. Q. Cunha ◽  
M. C. Roque-Barreira ◽  
R. M. D. Nogueira ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Inflammatory Responses ◽  
Neutrophil Migration ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Neutrophil Recruitment ◽  
Tnf Α ◽  
Inflammatory Stimuli

Inhibitory effect upon neutrophil migration to the inflammatory focus was previously detected in the cell-free incubation fluid of lipopolysaccharide (LPS)-stimulated macrophage monolayers. In the present study we showed that the neutrophil recruitment inhibitory activity from this supernatant was mainly detected in a fraction (P2) obtained by gel filtration chromatography on Sephacryl S-300. P2 fraction was able to inhibit ‘in vivo’ neutrophil emigration induced by different inflammatory stimuli, but it did not affect ‘in vitro’ neutrophil chemotaxis induced by FMLP. When injected intravenously, P2 inhibited oedema induced by carrageenin or immunological stimulus but not the oedema induced by dextran, thus affecting cell-dependent inflammatory responses. It was observed that P2 also induced neutrophil migration when injected locally in peritoneal cavities. This activity was significantly reduced by pretreatment of the animals with dexamethasone. Cytokines, such as IL-8 and TNF-α that are known to exhibit inhibitory effect upon neutrophil migration, were not detected in P2 fraction by highly sensitive assays. Overall the results suggest the existence of a novel cytokine exhibiting ‘in vivo’ neutrophil inhibitory activity, referred as NRIF.

scholarly journals Inhibitory Effect of Methyleugenol on IgE-Mediated Allergic Inflammation in RBL-2H3 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Feng Tang ◽  
Feilong Chen ◽  
Xiao Ling ◽  
Yao Huang ◽  
Xiaomei Zheng ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Allergic Inflammation ◽  
Allergic Diseases ◽  
Inhibitory Effect ◽  
Prostaglandin E ◽  
Therapeutic Drugs ◽  
Cytosolic Phospholipase ◽  
Ige Mediated ◽  
Cox 2 ◽  
Mast Cell Line

Allergic diseases, such as asthma and allergic rhinitis, are common. Therefore, the discovery of therapeutic drugs for these conditions is essential. Methyleugenol (ME) is a natural compound with antiallergic, antianaphylactic, antinociceptive, and anti-inflammatory effects. This study examined the antiallergic effect of ME on IgE-mediated inflammatory responses and its antiallergy mechanism in the mast cell line, RBL-2H3. We found that ME significantly inhibited the release ofβ-hexosaminidase, tumor necrosis factor- (TNF-)α, and interleukin- (IL-) 4, and was not cytotoxic at the tested concentrations (0–100 μM). Additionally, ME markedly reduced the production of the proinflammatory lipid mediators prostaglandin E2(PGE2), prostaglandin D2(PGD2), leukotriene B4(LTB4), and leukotriene C4(LTC4). We further evaluated the effect of ME on the early stages of the FcεRI cascade. ME significantly inhibited Syk phosphorylation and expression but had no effect on Lyn. Furthermore, it suppressed ERK1/2, p38, and JNK phosphorylation, which is implicated in proinflammatory cytokine expression. ME also decreased cytosolic phospholipase A2(cPLA2) and 5-lipoxygenase (5-LO) phosphorylation and cyclooxygenase-2 (COX-2) expression. These results suggest that ME inhibits allergic response by suppressing the activation of Syk, ERK1/2, p38, JNK, cPLA2, and 5-LO. Furthermore, the strong inhibition of COX-2 expression may also contribute to the antiallergic action of ME. Our study provides further information about the biological functions of ME.

scholarly journals Inhibitory Effect of Chunghyul-dan on Stroke Recurrence in Small Vessel Disease Patients: A 5-Year Observational Study

2018 ◽  
Vol 23 ◽  
pp. 2515690X1878937 ◽  
Author(s):  
Woo-Sang Jung ◽  
In Kyu Min ◽  
Chul Jin ◽  
Joo Young Park ◽  
Hyung Gyu Kim ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Primary Outcome ◽  
Small Vessel Disease ◽  
Recurrent Stroke ◽  
Inhibitory Effect ◽  
Small Vessel ◽  
Secondary Outcome ◽  
Stroke Recurrence ◽  
Drug Compliance

We investigated the stroke recurrence rate and the rate of adverse effects induced by an herbal medicine, Chunghyul-dan, administered to patients over a 5-year period. We prescribed 600 mg Chunghyul-dan a day to patients with small vessel diseases and investigated stroke recurrence, adverse effects, and drug compliance for 5 years. The primary outcome was the prevalence of stroke recurrence (in 3, 4, and 5 years). The secondary outcome was the frequency of adverse effects induced by Chunghyul-dan. We recruited 400 patients. Among them, 270, 233, and 195 patients completed 3, 4, and 5 years of follow-up, respectively. Among patients who completed 3, 4, and 5 years of follow-up, cumulative recurrent stroke occurred in 7 (2.6%), 11 (4.7%), and 12 (6.2%) patients. There were no adverse effects. We suggest that Chunghyul-dan might be useful for the inhibition of stroke recurrence by reducing microangiography progression. Further study is needed to confirm our hypothesis.

Inhibition of Peripheral TNF-α and Downregulation of Microglial Activation by Alpha-Lipoic Acid and Etanercept Protect Rat Brain Against Ischemic Stroke

2015 ◽  
Vol 53 (7) ◽  
pp. 4961-4971 ◽  
Author(s):  
Ming-Hsiu Wu ◽  
Chao-Ching Huang ◽  
Chung-Ching Chio ◽  
Kuen-Jer Tsai ◽  
Ching-Ping Chang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Rat Brain ◽  
Lipoic Acid ◽  
Microglial Activation ◽  
Alpha Lipoic Acid ◽  
Tnf Α

scholarly journals MicroRNA-155-5p promotes neuroinflammation and central sensitization via inhibiting SIRT1 in a nitroglycerin-induced chronic migraine mouse model

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Qianwen Wen ◽  
Yunfeng Wang ◽  
Qi Pan ◽  
Ruimin Tian ◽  
Dunke Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Chronic Migraine ◽  
Central Sensitization ◽  
Cellular Localization ◽  
Microglial Activation ◽  
Inflammatory Responses ◽  
Neurological Diseases ◽  
Thermal Hyperalgesia ◽  
Qrt Pcr ◽  
Tnf Α

Abstract Background Previous studies have confirmed that the microglial activation and subsequent inflammatory responses in the trigeminal nucleus caudalis (TNC) are involved in the central sensitization of chronic migraine (CM). MicroRNA-155-5p has been shown to modulate the polarization of microglia and participate in inflammatory processes in a variety of neurological diseases. However, its role in CM remains unclear. The purpose of this study was to determine the precise role of miR-155-5p in CM. Methods A model of CM in C57BL/6 mice was established by recurrent intraperitoneal injection of nitroglycerin (NTG). Mechanical and thermal hyperalgesia were evaluated by Von Frey filaments and radiant heat. The expression of miR-155-5p was examined by qRT-PCR, and the mRNA and protein levels of silent information regulator 1(SIRT1) were measured by qRT-PCR, Western blotting (WB) and immunofluorescence (IF) analysis. The miR-155-5p antagomir, miR-155-5p agomir, SRT1720 (a SIRT1 activator) and EX527 (a SIRT1 inhibitor) were administered to confirm the effects of miR-155-5p and SIRT1 on neuroinflammation and the central sensitization of CM. ELISA, WB and IF assays were applied to evaluate the expression of TNF-α, myeloperoxidase (MPO), IL-10, p-ERK, p-CREB, calcitonin gene-related peptide (CGRP), c-Fos and microglial activation. The cellular localization of SIRT1 was illustrated by IF. Results After the NTG-induced mouse model of CM was established, the expression of miR-155-5p was increased. The level of SIRT1 was decreased, and partly colocalized with Iba1 in the TNC. The miR-155-5p antagomir and SRT1720 downregulated the expression of p-ERK, p-CREB, CGRP, and c-Fos, alleviating microglial activation and decreasing inflammatory substances (TNF-α, MPO). The administration of miR-155-5p agomir or EX527 exacerbated neuroinflammation and central sensitization. Importantly, the miR-155-5p agomir elevated CGRP and c-Fos expression and microglial activation, which could subsequently be alleviated by SRT1720. Conclusions These data demonstrate that upregulated miR-155-5p in the TNC participates in the central sensitization of CM. Inhibiting miR-155-5p alleviates neuroinflammation by activating SIRT1 in the TNC of CM mice.

scholarly journals Ion Transport Modulators Differentially Modulate Inflammatory Responses in THP-1-Derived Macrophages

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Steven C. Mitini-Nkhoma ◽  
Narmada Fernando ◽  
G. K. D. Ishaka ◽  
Shiroma M. Handunnetti ◽  
Sisira L. Pathirana
Keyword(s):  
Nitric Oxide ◽  
Ion Transport ◽  
Inflammatory Responses ◽  
Inhibitory Effect ◽  
Superoxide Production ◽  
Noncommunicable Diseases ◽  
Nitric Oxide Production ◽  
Oxide Production ◽  
Tnf Α ◽  
Inflammatory Processes

Ion transport modulators are most commonly used to treat various noncommunicable diseases including diabetes and hypertension. They are also known to bind to receptors on various immune cells, but the immunomodulatory properties of most ion transport modulators have not been fully elucidated. We assessed the effects of thirteen FDA-approved ion transport modulators, namely, ambroxol HCl, amiloride HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide, metformin, omeprazole, pantoprazole, phenytoin, verapamil, drug X, and drug Y on superoxide production, nitric oxide production, and cytokine expression by THP-1-derived macrophages that had been stimulated with ethanol-inactivated Mycobacterium bovis BCG. Ambroxol HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide, metformin, pantoprazole, phenytoin, verapamil, and drug Y had an inhibitory effect on nitric oxide production, while all the test drugs had an inhibitory effect on superoxide production. Amiloride HCl, diazoxide, digoxin, furosemide, phenytoin, verapamil, drug X, and drug Y enhanced the expression of IL-1β and TNF-α. Unlike most immunomodulatory compounds currently in clinical use, most of the test drugs inhibited some inflammatory processes while promoting others. Ion pumps and ion channels could therefore serve as targets for more selective immunomodulatory agents which do not cause overt immunosuppression.

scholarly journals Myrrh Inhibits LPS-Induced Inflammatory Response and Protects from Cecal Ligation and Puncture-Induced Sepsis

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Min-Sun Kim ◽  
Gi-Sang Bae ◽  
Kyoung-Chel Park ◽  
Bon Soon Koo ◽  
Byung-Jin Kim ◽  
...  
Keyword(s):  
Inflammatory Mediators ◽  
Inflammatory Responses ◽  
Cecal Ligation ◽  
Inhibitory Effect ◽  
Peritoneal Macrophages ◽  
Prostaglandin E ◽  
Cecal Ligation And Puncture ◽  
Extracellular Signal ◽  
Alanine Aminotransferase Level ◽  
Anti Inflammatory

Myrrh has been used as an antibacterial and anti-inflammatory agent. However, effect of myrrh on peritoneal macrophages and clinically relevant models of septic shock, such as cecal ligation and puncture (CLP), is not well understood. Here, we investigated the inhibitory effect and mechanism(s) of myrrh on inflammatory responses. Myrrh inhibited LPS-induced productions of inflammatory mediators such as nitric oxide, prostaglandin E2, and tumor necrosis factor-αbut not of interleukin (IL)-1βand IL-6 in peritoneal macrophages. In addition, Myrrh inhibited LPS-induced activation of c-jun NH2-terminal kinase (JNK) but not of extracellular signal-regulated kinase (ERK), p38, and nuclear factor-κB. Administration of Myrrh reduced the CLP-induced mortality and bacterial counts and inhibited inflammatory mediators. Furthermore, administration of Myrrh attenuated CLP-induced liver damages, which were mainly evidenced by decreased infiltration of leukocytes and aspartate aminotransferase/alanine aminotransferase level. Taken together, these results provide the evidence for the anti-inflammatory and antibacterial potential of Myrrh in sepsis.

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