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.
Abbreviations
- ALA:
-
α-Linolenic acid
- BSA:
-
Bovine serum albumin
- DHA:
-
Docosahexaenoic acid
- DMEM:
-
Dulbecco’s modified Eagle’s medium
- FBS:
-
Foetal bovine serum
- EPA:
-
Eicosapentaenoic acid
- ERK:
-
Extracellular signal regulated kinase
- JNK:
-
c-jun N terminal kinase
- iNOS:
-
Inducible nitric oxide synthase
- IκB:
-
Inhibitor of κB
- LDH:
-
Lactate dehydrogenase
- LPS:
-
Lipopolysaccharide
- MAPK:
-
Mitogen-activated protein kinases
- MTT:
-
3-(4,5-Dimethyl thiazol 2-yl)-2,5-diphenyltetrazolium
- NO:
-
Nitric oxide
- NFκB:
-
Nuclear factor κB
- n-3 PUFA:
-
Omega-3 polyunsaturated fatty acids
- PBS:
-
Dulbecco’s phosphate-buffered saline
- SDA:
-
Stearidonic acid
References
Calder PC (2006) n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83:1505S–1519S
Marik PE, Varon J (2009) Omega-3 dietary supplements and the risk of cardiovascular events: a systematic review. Clin Cardiol 32:365–372
Farzaneh-Far R, Harris WS, Garg S, Na B, Whooley MA (2009) Inverse association of erythrocyte n-3 fatty acid levels with inflammatory biomarkers in patients with stable coronary artery disease: the heart and soul study. Atherosclerosis 205:538–543
Ferrucci L, Cherubini A, Bandinelli S, Bartali B, Corsi A, Lauretani F, Martin A, Andres-Lacueva C, Senin U, Guralnik JM (2006) Relationship of plasma polyunsaturated fatty acids to circulating inflammatory markers. J Clin Endocrinol Metab 91:439–446
Rangel-Huerta OD, Aguilera CM, Mesa MD, Gil A (2012) Omega-3 long-chain polyunsaturated fatty acids supplementation on inflammatory biomakers: a systematic review of randomised clinical trials. Br J Nutr 107:S159–S170
Lo CJ, Chiu KC, Fu M, Lo R, Helton S (1999) Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NFkappaB activity. J Surg Res 82:216–221
Mullen A, Loscher CE, Roche HM (2010) Anti-inflammatory effects of EPA and DHA are dependent upon time and dose-response elements associated with LPS-stimulation in THP-1-derived macrophages. J Nutr Biochem 21:444–450
Chakraborty M, Bhattacharya S, Mishra R, Saha SS, Bhattacharjee P, Dhar P, Mishra R (2015) Combination of low dose major n3 PUFAs in fresh water mussel lipid is an alternative of EPA-DHA supplementation in inflammatory conditions of arthritis and LPS stimulated macrophages. PharmaNutrition 3:67–75
Venegas-Caleron M, Sayanova O, Napier JA (2010) An alternative to fish oils: metabolic engineering of oil-seed crops to produce omega-3 long chain polyunsaturated fatty acids. Prog Lipid Res 49:108–119
Guil-Guerrero JL (2007) Stearidonic acid (18:4n-3): metabolism, nutritional importance, medical uses and natural sources. Eur L Lipid Technol 109:1226–1236
Horia E, Watkins BA (2005) Comparison of stearidonic acid and α-linolenic acid on PGE2 production and COX-2 protein levels in MDA-MB-231 breast cancer cell cultures. J Nutr Biochem 16:184–192
Guil-Guerrero J (2007) Stearidonic acid: metabolism, nutritional importance, medical uses and natural sources. Eur J Lipid Sci Technol 109:1226–1236
Baik JY, Kim NH, Oh SW, Kim IH (2015) Preparation of highly purified stearidonic acid from echium oil via an enzymatic method combined with preparative high performance liquid chromatography. J Oleo Sci 64:729–736
Lee JH, Shin JA, Lee JH, Lee KT (2004) Production of lipase-catalyzed structured lipids from safflower oil with conjugated linoleic acid and oxidation studies with rosemary extracts. Food Res Int 37:967–974
Guo W, Wong S, Xie W, Lei T, Luo Z (2007) Palmitate modulates intracellular signaling, induces endoplasmic reticulum stress, and causes apoptosis in mouse 3T3-L1 and rat primary preadipocytes. Am J Physiol Endocrinol Metab 293:E576–E586
Sung J, Lee J (2015) Anti-inflammatory activity of butein and luteolin through suppression of NFκB activation and induction of heme oxygenase-1. J Med Food 18:557–564
Fotakis G, Timbrell JA (2006) In vitro cytotoxicity assays: comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett 160:171–177
Lopez-Garcia J, Lehocky M, Humpolicek P, Saha P (2014) HaCaT keratinocytes response on antimicrobial atelocollagen substrates: extent of cytotoxicity, cell viability and proliferation. J Funct Biomater 5:43–57
Pondugula SR, Ferniany G, Ashraf F, Abbot KL, Smith BF, Goleman ES, Mansour M, Bird RC, Smith AN, Karthikeyan C, Trivedi P, Tiwari AK (2015) Stearidonic acid, a plant-based dietary fatty acid, enhances the chemosensitivity of canine lymphoid tumor cells. Biochem Biophys Res Commun 460:1002–1007
Anderton MJ, Manson MM, Verschoyle R, Gescher A, Steward WP, Williams ML, Mager DE (2004) Physiological modeling of formulated and crystalline 3,3′-diindolylmethane pharmacokinetics following oral administration in mice. Drug Metab Dispos 32:632–638
Kuriki K, Nagaya T, Tokudome Y, Imaeda N, Fujiwara N, Sato J, Goto C, Ikeda M, Maki S, Tajima K, Tokudome S (2003) Plasma concentrations of (n-3) highly unsaturated fatty acids are good biomarkers of relative dietary fatty acid intakes: a cross-sectional study. J Nutr 133:3643–3650
De Boer AA, Monk JM, Robinson LE (2014) Docosahexaenoic acid decreases pro-inflammatory mediators in an in vitro murine adipocyte macrophage co-culture model. PLoS One 9:1–12
Chen HG, Xie KL, Han HZ, Wang WN, Liu DQ, Wang GL, Yu YH (2013) Heme oxygenase-1 mediates the anti-inflammatory effect of molecular hydrogen in LPS-stimulated RAW 264.7 macrophages. Int J Surg 11:1060–1066
Leyva-Lopez N, Nair V, Bang WY, Cisneros-Zevallos L, Heredia JB (2016) Protective role of terpenes and polyphenols from three species of Oregano (Lippia graveolens, Lippia palmeri and Hedeoma patens) on the suppression of lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells. J Ethnopharmacol 187:302–312
Chen H, Sohn J, Zhang L, Tian J, Chen S, Bjeldanes LF (2014) Anti-inflammatory effects of chicanine on murine macrophage by down-regulating LPS-induced inflammatory cytokines in IkappaBalpha/MAPK/ERK signaling pathways. Eur J Pharmacol 724:168–174
Srisook K, Palachot M, Mongkol N, Srisook E, Sarapusit S (2011) Anti-inflammatory effect of ethyl acetate extract from Cissus quadrangularis Linn may be involved with induction of heme oxygenase-1 and suppression of NF-kappaB activation. J Ethnopharmacol 133:1008–1014
Kaminska B (2005) MAPK signalling pathways as molecular targets for anti-inflammatory therapy from molecular mechanisms to therapeutic benefits. Biochim Biophys Acta 1754:253–262
Walker CG, Jebb SA, Calder PC (2013) Stearidonic acid as a supplemental source of ω-3 polyunsaturated fatty acids to enhance status for improved human health. Nutrition 29:363–369
Jeong DH, Kim KB, Kim MJ, Kang BK, Ahn DH (2016) Skipjack tuna (Katsuwonus pelamis) eyeball oil exerts an anti-inflammatory effect by inhibiting NF-kappaB and MAPK activation in LPS-induced RAW 264.7 cells and croton oil-treated mice. Int Immunopharmacol 40:50–56
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Sung, J., Jeon, H., Kim, IH. et al. Anti-Inflammatory Effects of Stearidonic Acid Mediated by Suppression of NF-κB and MAP-Kinase Pathways in Macrophages. Lipids 52, 781–787 (2017). https://doi.org/10.1007/s11745-017-4278-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11745-017-4278-6