scholarly journals Docosahexaenoic fatty acid reduces the pro‐inflammatory response induced by IL-1β in astrocytes through inhibition of NF-κB and AP-1 transcription factor activation

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Emilia Zgórzyńska ◽  
Dawid Stulczewski ◽  
Barbara Dziedzic ◽  
Kuan-Pin Su ◽  
Anna Walczewska

Abstract Background Astrocytes are responsible for a broad range of functions that maintain homeostasis in the brain. However, their response to the pro-inflammatory cytokines released by activated microglia in various neurological pathologies may exacerbate neurodegenerative processes. Accumulating evidence suggests that omega-3 docosahexaenoic fatty acid (DHA) has an anti-inflammatory effect in various cell cultures studies and in a variety of neurological disorders. In this study we examined the mechanism involved in the inhibition of the pro-inflammatory response by DHA in astrocytes treated with IL-1β. Methods and results Activation of the transcription factors NF-κB and AP-1 was measured in IL-1β-treated primary astrocytes incubated with various concentrations of DHA. COX-2 and iNOS protein expression was determined by Western blot, and TNF-α and IL-6 secretion was measured using ELISA-based assays. DHA treatment inhibited translocation of p65NF-κB to the nucleus, significantly lowered p65NF-κB protein level and fluorescence of p65NF-κB in the nucleus, reduced dose-dependently IκB protein phosphorylation, and the binding of the AP-1 transcription factor members (c-Jun/c-Fos) to the specific TPA-response element (TRE) of DNA. In addition, the expression of pro-inflammatory COX-2 and iNOS proteins was downregulated and TNF-α and IL-6 secretion was also reduced. Conclusions These results indicate that DHA is a powerful factor that reduces the pro-inflammatory response in astrocytes. Consequently, successful introduction of DHA into the astrocyte membranes can attenuate neuroinflammation, which is a key factor of age-related neurodegenerative disorders.

Marine Drugs ◽  
2020 ◽  
Vol 19 (1) ◽  
pp. 1
Author(s):  
Peeraporn Varinthra ◽  
Shun-Ping Huang ◽  
Supin Chompoopong ◽  
Zhi-Hong Wen ◽  
Ingrid Y. Liu

Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer’s disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ1-42 oligomer (oAβ1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells treated with oAβ1-42 without causing any cytotoxicity or notable side effects. This study suggests that 4-PSB-2 is a promising drug candidate for attenuation of AMD.


2018 ◽  
Vol 88 (5-6) ◽  
pp. 309-318
Author(s):  
Hae Seong Song ◽  
Jung-Eun Kwon ◽  
Hyun Jin Baek ◽  
Chang Won Kim ◽  
Hyelin Jeon ◽  
...  

Abstract. Sorghum bicolor L. Moench is widely grown all over the world for food and feed. The effects of sorghum extracts on general inflammation have been previously studied, but its anti-vascular inflammatory effects are unknown. Therefore, this study investigated the anti-vascular inflammation effects of sorghum extract (SBE) and fermented extract of sorghum (fSBE) on human aortic smooth muscle cells (HASMCs). After the cytotoxicity test of the sorghum extract, a series of experiments were conducted. The inhibition effects of SBE and fSBE on the inflammatory response and adhesion molecule expression were measured using treatment with tumor necrosis factor-α (TNF-α), a crucial promoter for the development of atherosclerotic lesions, on HASMCs. After TNF-α (10 ng/mL) treatment for 2 h, then SBE and fSBE (100 and 200 μg/mL) were applied for 12h. Western blotting analysis showed that the expression of vascular cell adhesion molecule-1 (VCAM-1) (2.4-fold) and cyclooxygenase-2 (COX-2) (6.7-fold) decreased, and heme oxygenase-1 (HO-1) (3.5-fold) increased compared to the TNF-α control when treated with 200 μg/mL fSBE (P<0.05). In addition, the fSBE significantly increased the expression of HO-1 and significantly decreased the expression of VCAM-1 and COX-2 compared to the TNF-α control in mRNA level (P<0.05). These reasons of results might be due to the increased concentrations of procyanidin B1 (about 6-fold) and C1 (about 30-fold) produced through fermentation with Aspergillus oryzae NK for 48 h, at 37 °C. Overall, the results demonstrated that fSBE enhanced the inhibition of the inflammatory response and adherent molecule expression in HASMCs.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 111-111
Author(s):  
Kingsley Kalu ◽  
Angelica Ly ◽  
Charles McMonnies ◽  
Jayashree Arcot

Abstract Objectives The aim of this study was to assess the dietary intakes of lutein, zeaxanthin (L + Z) and omega-3-essential fatty acid(EFA) among a selected population of Australian based adults and to examine the effect of specified risk factors for age-related macular degeneration(AMD) on those levels. Methods A cross-sectional study involving 70 adults aged 19–52 years was carried out. Demographic data were obtained using an online self-administered questionnaire while dietary intakes were estimated using USDA's 24 hours recall questionnaire, the Victorian Cancer Council(Australia) food frequency questionnaire and anthropometric characteristics were obtained using a body composition analyzer. Dietary intakes of lutein, zeaxanthin, omega-3-EFA and anthropometric indices against the risk of AMD were established using descriptive statistics and Spearman correlation. Results The mean age of the population was 29.9 ± 8.1years with 51% men and 49% women. Women had a higher intake of L + Z (1908.6 μg/day versus 1032.8 μg/day) and alpha-linolenic acid(ALA) compared to men(1.7 ± 1.1 g/day versus 1.6 ± 1.2 g/day). Men consumed more omega-3-EFA than women (433 ± 397.1 mg/day versus 365 ± 210.7 mg/day). L + Z levels were higher among people of Middle Eastern and South Asian origin (&gt;4000 μg/day) in the 19–25years age group. People of Middle Eastern, South East Asian and South Asian had the highest intake of omega-3-EFA(&gt;500 mg/day) at ages 19–25, 26–32 and 34–52years respectively. Women aged 34–52years with a family history of AMD had higher levels of L + Z(&gt;2500 μg/day) while women aged 26–32years with a family history of AMD had higher levels of ALA(&gt;3 g/day). Ethnicity and L + Z were correlated (P = −0.456, P &lt; 0.02). Higher levels of intake of L + Z (&gt;4000 μg/day) were seen in participants aged 34–52years with a 5–10years residence in Australia. Participants who had less than 5–10years of residency had higher levels of omega-3-EFA(&gt;500 mg/day) for ages 26–32years while those aged 34–52years who had less than 5years of residency had higher ALA(&gt;4 g/day). Conclusions Intake levels for L + Z vary significantly among participants. Culturally specific dietary habits could feasibly influence the levels of intake of L + Z. Intake levels of omega-3-EFA were met. This study provides detailed intake levels of L + Z and omega-3-EFA for the ‘at-risk’ AMD group. Funding Sources No funding source.


2018 ◽  
Vol 73 (7-8) ◽  
pp. 273-279 ◽  
Author(s):  
Chang-Suk Kong ◽  
Jung Im Lee ◽  
Fatih Karadeniz ◽  
Hojun Kim ◽  
Youngwan Seo

Abstract The Arctic flora hosts a limited number of species due to its extreme environmental conditions which also yield novel and unique secondary metabolites from withstanding plants. Considering a lack of research on bioactivity potential of Arctic flora, Ranunculus hyperboreus, an Arctic plant, was studied for its anti-inflammatory potential as a part of ongoing research on discovering novel natural bioactive products. Solvent-based fractions (H2O, n-BuOH, 85% aq. MeOH, n-hexane) from R. hyperboreus extract were observed to decrease the elevated nitrate amount during the inflammatory response of lipopolysaccharide-induced mouse macrophage RAW264.7 cells. To some extent, treatment with fractions was able to regulate the expression and protein levels of inflammation-related enzymes, iNOS and COX-2, and pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6. The most active fractions, H2O and 85% aq. MeOH, were suggested to exert their effect through suppressed activation of MAPK pathways, especially JNK. Based on the studies of same species, phenolic glycosides were suggested to be the main active ingredients. To our knowledge, this is the first report of any bioactivity of R. hyperboreus which could be a valuable source of natural bioactive agents against inflammation.


2021 ◽  
Vol 22 (21) ◽  
pp. 11859
Author(s):  
Elodie Passeri ◽  
Kamil Elkhoury ◽  
Maria Camila Jiménez Garavito ◽  
Frédéric Desor ◽  
Marion Huguet ◽  
...  

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) play an important role in the development, maintenance, and function of the brain. Dietary supplementation of n-3 PUFAs in neurological diseases has been a subject of particular interest in preventing cognitive deficits, and particularly in age-related neurodegeneration. Developing strategies for the efficient delivery of these lipids to the brain has presented a challenge in recent years. We recently reported the preparation of n-3 PUFA-rich nanoliposomes (NLs) from salmon lecithin, and demonstrated their neurotrophic effects in rat embryo cortical neurons. The objective of this study was to assess the ability of these NLs to deliver PUFAs in cellulo and in vivo (in mice). NLs were prepared using salmon lecithin rich in n-3 PUFAs (29.13%), and characterized with an average size of 107.90 ± 0.35 nm, a polydispersity index of 0.25 ± 0.01, and a negative particle-surface electrical charge (−50.4 ± 0.2 mV). Incubation of rat embryo cortical neurons with NLs led to a significant increase in docosahexaenoic acid (DHA) (51.5%, p < 0.01), as well as palmitic acid, and a small decrease in oleic acid after 72 h (12.2%, p < 0.05). Twenty mice on a standard diet received oral administration of NLs (12 mg/mouse/day; 5 days per week) for 8 weeks. Fatty acid profiles obtained via gas chromatography revealed significant increases in cortical levels of saturated, monounsaturated, and n-3 (docosahexaenoic acid,) and n-6 (docosapentaenoic acid and arachidonic acid) PUFAs. This was not the case for the hippocampus or in the liver. There were no effects on plasma lipid levels, and daily monitoring confirmed NL biocompatibility. These results demonstrate that NLs can be used for delivery of PUFAs to the brain. This study opens new research possibilities in the development of preventive as well as therapeutic strategies for age-related neurodegeneration.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Helena Fisk ◽  
Rob Ayres ◽  
Caroline Childs ◽  
Elizabeth Miles ◽  
Rebecca Clarke-Harris ◽  
...  

AbstractIntroduction:Obesity is an excess of adipose tissue (AT) and is linked with increased inflammation that enhances risk of type-2 diabetes and cardiovascular disease. The BIOCLAIMS study assessed the effect of obesity on AT fatty acid composition and gene expression, and the responses of these to chronic omega-3 FA supplementation.Materials and methods:AT biopsies were collected pre- and post-12 week supplementation with 1.1 g EPA + 0.8 g DHA/day or corn oil. The composition of FA in the total lipid extract of AT from 37 normal-weight and 44 obese subjects was assessed by gas chromatography, whole AT transcriptome from 10 normal-weight and 10 obese subjects was assessed by RNA-Sequencing, and selected gene expression in AT of 27 normal-weight and 38 obese subjects was assessed by qRT-PCR.Results:789 AT genes were differentially expressed (623 upregulated, 175 downregulated) in obesity compared to normal-weight (FC > 2, P < 0.05). Differentially expressed genes included EGFL6, MMP-7 and -9, 5-LOX, WNT3 and WNT10B, DACT2, CNR1, SLC27A2 and PLA2G7, and were associated with immune and inflammatory response, cell proliferation, activation and movement, Wnt signalling, remodelling and expansion, and lipid incorporation and degradation.Chronic supplementation with EPA + DHA increased the concentration of AT EPA, DPA and DHA in normal-weight subjects (P < 0.01), and EPA in obese subjects (P = 0.006). EPA + DHA modulated the expression of 26 genes (14 upregulated, 12 downregulated) in normal-weight subjects and 7 genes (3 upregulated, 5 downregulated) in obese subjects (FC > 2, P < 0.05). Of note, EPA + DHA downregulated IGLV1-44, IGLV1-51, PROK2, and TREM1 in normal weight subjects (P < 0.05), and IGLV1-44, IGLV1-47, DACT2 and IDO1 obese subjects (P < 0.05). Genes of note upregulated by EPA + DHA included KCNH2, GCGR, SLC36A2 and FOXC2 in normal-weight subjects, and MAB21L1, LRRTM4, and COX-2, in obese subjects. Differentially expressed genes were associated with a decrease in complement activation and immunoglobulin secretion, negative regulation of cell proliferation, and positive regulation of remodelling, amino acid and glucose transport, and COX pathway metabolite synthesis.Discussion:These data indicate an altered AT transcription profile and gene expression in obesity suggesting enhanced immune and inflammatory response, tissue expansion and remodelling, and changes to lipid metabolism, as well as dysregulation in response to supplementary EPA + DHA at a gene expression level. EPA + DHA are able to modulate AT gene expression predominantly associated with reducing immune response, but obesity may involve resistance to the effects on tissue remodelling and nutrient transport.


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