Anti‐Inflammatory Effects of Stearidonic Acid Mediated by Suppression of NF‐κB and MAP‐Kinase Pathways in Macrophages

Abstract

Stearidonic acid (SDA, 18:4n-3) is an omega-3 polyunsaturated fatty acid present in oils derived from plants of the Boraginaceae family. In this study, we determined the anti-inflammatory effects of SDA isolated from echium oil on lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages. SDA significantly downregulated the levels of the inducible nitric oxide synthase (iNOS) protein, thereby suppressing the production of nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. In addition, SDA inhibited the nuclear translocation and promoter activity of nuclear factor κB (NFκB) and the phosphorylation of mitogen-activated protein kinases (MAPK) such as extracellular signal regulated kinase 1/2, c-jun N terminal kinase, and p38 in LPS-stimulated RAW 264.7 cells. Our results showed that SDA exerted anti-inflammatory effects by suppressing iNOS-mediated NO production via inactivation of NFκB and MAPK signaling pathways.

Effects of Omega-3 Fatty Acids on Immune Cells

“…Decreased LPS-induced phosphorylation, nuclear translocation, and transcriptional activity of NFkB by pre-treatment with omega-3 fatty acids have been demonstrated in primary macrophages and macrophage cell lines with EPA, DHA, or the plant-derived omega-3 fatty acid steridonic acid [32,33,46,47]. EPA and DHA are also able to decrease NFkB activation induced by the TLR2 ligand PamCAG [46].…”

“…EPA and DHA are also able to decrease NFkB activation induced by the TLR2 ligand PamCAG [46]. Decreased activation by EPA or DHA treatment has also been described for other transcription factors such as IRF3, STAT-1, STAT-3, IRF1, ERK1/2, JNK, and MAPK [28,47] but not for others such as CREB [34]. However, how omega-3 fatty acids exert this modulation on inflammatory transcription factors activation remains largely unknown.…”

“…However, how omega-3 fatty acids exert this modulation on inflammatory transcription factors activation remains largely unknown. It has been shown that DHA and other ALA derivatives decrease ROS and NO production [33,47] in LPS-stimulated macrophages, which could be associated with decreased transcription factor activation. Also, DHA and EPA have been found to regulate miRNA expression in Raw and THP-1-derived macrophages that could add an additional regulatory level of the inflammatory transcription factors [25,48].…”

Washed microbiota transplantation vs. manual fecal microbiota transplantation: clinical findings, animal studies and in vitro screening

“…In Supernatant 3, a total of 13 anti-inflammatory metabolites were noted. Many of them can inhibit the activation of the LPS-induced NF-κB signaling pathway to reduce the inflammatory response, including tretinoin (Austenaa et al, 2009), stearidonic acid (Sung et al, 2017), caffeic acid (Kim et al, 2014), tyrosol (Lu et al, 2013), aspirin (Liu et al, 2017), 4-hydroxy-2-nonenal (Kim et al, 2009). Resveratrol (Bigagli et al, 2017), chloral hydrate (Cai et al, 2016) and paracetamol (Vuong et al, 2019) have antiinflammatory and anti-oxidant effects in LPS-stimulated RAW 264.7 macrophage cells in vitro.…”

Possible Health Effects of a Wax Ester Rich Marine Oil

“…(2011) found a reduced IL-6 secretion in LPS-stimulated adipose stem cells from ob/ob mice due to a suppressed TLR2 expression and a decreased activity of NF-κB. SDA also downregulated the levels of inducible nitric oxide synthesis (iNOS) protein, the translocation of NF-κB and the phosphorylation of mitogen-activated protein kinases (MAPK) in LPS-induced (M1) macrophages ( Sung et al., 2017 ).…”