Upregulation of Suppressor of Cytokine Signaling 3 in Microglia by Cinnamic Acid

Chakrabarti, Sudipta; Jana, Malabendu; Roy, Avik; Pahan, Kalipada

doi:10.2174/1567205015666180507104755

Cited by 27 publications

(20 citation statements)

References 53 publications

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“…To verify the effect of tested compounds on NF-κB activity, the secretion of TNF-α, which is under its transcription control [44], was measured. CA is known for its ability to attenuate the production of this pro-inflammatory cytokine in vitro and in vivo [45,46]. In our experiment, pure CA did not affect the TNF-α production, see Figure 7.…”

Section: Inhibition Of Tnf-α Secretionmentioning

confidence: 47%

Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

et al. 2019

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A series of sixteen ring-substituted N-arylcinnamanilides, previously described as highly antimicrobially effective against a wide spectrum of bacteria and fungi, together with two new derivatives from this group were prepared and characterized. Moreover, the molecular structure of (2E)-N-(2-bromo-5-fluorophenyl)-3-phenylprop-2-enamide as a model compound was determined using single-crystal X-ray analysis. All the compounds were tested for their anti-inflammatory potential, and most tested compounds significantly attenuated the lipopolysaccharide-induced NF-κB activation and were more potent than the parental cinnamic acid. (2E)-N-[2-Chloro-5-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide, (2E)-N-(2,6-dibromophenyl)-3-phenylprop-2-enamide, and (2E)-N-(2,5-dichlorophenyl)-3-phenylprop-2-enamide demonstrated the highest inhibition effect on transcription factor NF-κB at the concentration of 2 µM and showed a similar effectiveness as the reference drug prednisone. Several compounds also decreased the level of TNF-α. Nevertheless, subsequent tests showed that the investigated compounds affect neither IκBα level nor MAPKs activity, which suggests that the N-arylcinnamanilides may have a different mode of action to prednisone. The modification of the C (2,5) or C (2,6) positions of the anilide core by rather lipophilic and bulky moieties seems to be preferable for the anti-inflammatory potential of these compounds.Molecules 2019, 24, 4531 2 of 15 drugs are directly obtained from plants or fungi or are "nature-inspired" [11]. One such molecule is cinnamic acid (CA). It is a small organic molecule, which can be found in many kinds of plants in pure form or as a part of more complicated structures. CA and its natural and synthetic derivatives possess many interesting biological effects, such as antimicrobial [12,13], anticancer [14], anti-oxidant [13], and anti-inflammatory activities [15].N-Arylcinnamides represent a group of synthetic derivatives of CA. This group of compounds possesses several potentially active moieties-styryl, amide (peptide-like [16]) bond, and aryl [17][18][19][20][21][22]. Thus, cinnamides can be considered as a privilege structure or a scaffold (a part) of more complex molecules in medicinal chemistry [23,24] The series of N-arylcinnamide derivatives presented in this work was previously tested for their anti-microbial activity (compounds 1-15 and 17) [25,26], and three new derivatives 16 and 18 were prepared and characterized. Based on the concepts of polypharmacology, multifactorial diseases, and multitarget drugs [27], as well as the above-mentioned results, a group of eighteen N-arylcinnamanilides was chosen for the screening of their ability to moderate the inflammation-like reaction in vitro. Results and Discussion ChemistryThe investigated compounds (previously published compounds 1-15 and 17 [25] and two new compounds, 16 and 18) were prepared using a one-step microwave-assisted synthesis, see Scheme 1. Briefly, the carboxyl group of CA was activated with phosphorus trichloride, and then...

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Section: Inhibition Of Tnf-α Secretionmentioning

confidence: 47%

Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

et al. 2019

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“…In vitro studies have shown that upregulation of SOCS3 by cinnamic acid suppressed expression of iNOS, TNF-a, IL-1b, and IL-6 in LPS-triggered mouse BV-2 microglia. 88 Studies in LysMCre-SOCS3 fl/fl mice, which lack SOCS3 expression in myeloid lineage cells, demonstrated enhanced polarization of microglia towards a pro-inflammatory state as demarcated by increased production and secretion of TNF-a, IL-1b, IL-6, CCL3, CCL4, and CXCL11. 89 Histone H3K27me3 demethylase Jumonji domain containing 3 (Jmjd3) also plays a pivotal role in microglial polarization towards an anti-inflammatory phenotype.…”

Section: Dynamic Transition Between Microglia Activation Statesmentioning

confidence: 99%

Regulation of blood–brain barrier integrity by microglia in health and disease: A therapeutic opportunity

Ronaldson

Davis

2020

J Cereb Blood Flow Metab

239

180

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The blood–brain barrier (BBB) is a critical regulator of CNS homeostasis. It possesses physical and biochemical characteristics (i.e. tight junction protein complexes, transporters) that are necessary for the BBB to perform this physiological role. Microvascular endothelial cells require support from astrocytes, pericytes, microglia, neurons, and constituents of the extracellular matrix. This intricate relationship implies the existence of a neurovascular unit (NVU). NVU cellular components can be activated in disease and contribute to dynamic remodeling of the BBB. This is especially true of microglia, the resident immune cells of the brain, which polarize into distinct proinflammatory (M1) or anti-inflammatory (M2) phenotypes. Current data indicate that M1 pro-inflammatory microglia contribute to BBB dysfunction and vascular “leak”, while M2 anti-inflammatory microglia play a protective role at the BBB. Understanding biological mechanisms involved in microglia activation provides a unique opportunity to develop novel treatment approaches for neurological diseases. In this review, we highlight characteristics of M1 proinflammatory and M2 anti-inflammatory microglia and describe how these distinct phenotypes modulate BBB physiology. Additionally, we outline the role of other NVU cell types in regulating microglial activation and highlight how microglia can be targeted for treatment of disease with a focus on ischemic stroke and Alzheimer’s disease.

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“…Acute phase response (APR) organs include the brain (involved in the increased synthesis of corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), liver (involved in the increased synthesis of metallothionein and antioxidants to restore homeostasis of plasma proteins), bone marrow (increased thrombocytosis and reduced erythropoiesis), adrenal gland (increased cortisol production), and muscle (proteolysis) and adipose cells (altered lipid metabolism) (Robinson et al, 2016). The APR is regulated via interleukin 1 receptor antagonist (IL-1RA), IL-10, suppressor of cytokine signaling (SOCS) proteins, and transient expression of APP and their mRNA half-lives (McCormick et al, 2016; Chakrabarti et al, 2018). There are ~200 different APPs in animals.…”

Section: Acute Phase Proteinsmentioning

confidence: 99%

Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values

Dhama

Latheef

Dadar

et al. 2019

Front. Mol. Biosci.

211

172

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Various internal and external factors negatively affect the homeostatic equilibrium of organisms at the molecular to the whole-body level, inducing the so-called state of stress. Stress affects an organism's welfare status and induces energy-consuming mechanisms to combat the subsequent ill effects; thus, the individual may be immunocompromised, making them vulnerable to pathogens. The information presented here has been extensively reviewed, compiled, and analyzed from authenticated published resources available on Medline, PubMed, PubMed Central, Science Direct, and other scientific databases. Stress levels can be monitored by the quantitative and qualitative measurement of biomarkers. Potential markers of stress include thermal stress markers, such as heat shock proteins (HSPs), innate immune markers, such as Acute Phase Proteins (APPs), oxidative stress markers, and chemical secretions in the saliva and urine. In addition, stress biomarkers also play critical roles in the prognosis of stress-related diseases and disorders, and therapy guidance. Moreover, different components have been identified as potent mediators of cardiovascular, central nervous system, hepatic, and nephrological disorders, which can also be employed to evaluate these conditions precisely, but with stringent validation and specificity. Considerable scientific advances have been made in the detection, quantitation, and application of these biomarkers. The present review describes the current progress of identifying biomarkers, their prognostic, and therapeutic values.

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Upregulation of Suppressor of Cytokine Signaling 3 in Microglia by Cinnamic Acid

Cited by 27 publications

References 53 publications

Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

Investigation of Anti-Inflammatory Potential of N-Arylcinnamamide Derivatives

Regulation of blood–brain barrier integrity by microglia in health and disease: A therapeutic opportunity

Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values

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