Evaluation of the Anti-Inflammatory Activities of 5,8,11-cis-Eicosatrienoic Acid

DOI: 10.4236/fns.2013.49A1018   PDF   HTML   XML   3,998 Downloads   5,566 Views   Citations


The main eicosanoids inflammatory mediators, prostaglandins and leukotrienes, are both generated from arachidonic acid (AA; 20:4 n-6). AA is a member of polyunsaturated fatty acids (PUFAs). Numerous studies have demonstrated that various contents of PUFAs can modulate the inflammatory responses. However, fewer studies have examined n-9PUFAs and their effects on the inflammatory responses. In the present study, the role of 5,8,11-cis-eicosatrienoic acid (ETrA; 20:3 n-9, also called Mead acid) in the inflammatory responses has been investigated. The anti-inflammatory activities of ETrA were examined using an in vitro macrophage system and the inhibitory effect was confirmed by western blot analysis for iNOS and COX-2 expressions. The interactions between ETrA and COX-2 protein were simulated to produce a computer modeling protein-ligand complexes and the results suggest a possible mechanism for the effects of ETrA. In this study, we described a significant inhibition of the inflammatory activities initiated by ETrA. Since ETrA is a substance presented in the tissues of young animals, we therefore anticipate that ETrA can be utilized as a natural therapeutic supplement to inhibit inflammatory activities.

Share and Cite:

L. Hsu, Z. Wen, H. Chen, H. Lin, C. Chiu and H. Wu, "Evaluation of the Anti-Inflammatory Activities of 5,8,11-cis-Eicosatrienoic Acid," Food and Nutrition Sciences, Vol. 4 No. 9A, 2013, pp. 113-119. doi: 10.4236/fns.2013.49A1018.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] C. Nathan, “Points of Control in Inflammation,” Nature, Vol. 420, No. 6917, 2002, pp. 846-852. doi:10.1038/nature01320
[2] G. Srikrishna and H. H. Freeze, “Endogenous Damage-Associated Molecular Pattern Molecules at the Crossroads of Inflammation and Cancer,” Neoplasia, Vol. 11, No. 7, 2009, pp. 615-628.
[3] G. Folco, and R. C. Murphy, “Eicosanoid Transcellular Biosynthesis: From Cell-Cell Interactions to in Vivo Tissue Responses,” Pharmacological Reviews, Vol. 58, No. 3, 2006, pp. 375-388. doi:10.1124/pr.58.3.8
[4] J. Claria and M. Romano, “Pharmacological Intervention of Cyclooxygenase-2 and 5-Lipoxygenase Pathways. Impact on Inflammation and Cancer,” Current Pharmaceutical Design, Vol. 11, No. 26, 2005, pp. 3431-3447. doi:10.2174/138161205774370753
[5] P. C. Calder and G. C. Burdge, “Bioactive Lipids,” In: A. Nicolaou and G. Kokotos, Eds., Fatty Acids, The Oily Press, Bridgewater, 2004, pp. 1-36. doi:10.1533/9780857097934.1
[6] P. C. Calder, “Polyunsaturated Fatty Acids, Inflammatory Processes and Inflammatory Bowel Diseases,” Molecular Nutrition & Food Research, Vol. 52, No. 8, 2008, pp. 885-897. doi:10.1002/mnfr.200700289
[7] P. C. Calder, “Dietary Modification of Inflammation with Lipids,” Proceedings of the Nutrition Society, Vol. 61, No. 3, 2002, pp. 345-358. doi:10.1079/PNS2002166
[8] M. L. Salem, “Systemic Treatment with n-6 Polyunsaturated Fatty Acids Attenuates EL4 Thymoma Growth and Metastasis through Enhancing Specific and Non-Specific Anti-Tumor Cytolytic Activities and Production of TH1 Cytokines,” International Immunopharmacology, Vol. 5, No. 6, 2005, pp. 947-960. doi:10.1016/j.intimp.2004.12.013
[9] J. Thanasak, V. P. Rutten, J. T. Schonewille, A. Hoek, A. C. Beynen, J. P. Noordhuizen and K. E. Muller, “Effect of a Dietary n-6 Polyunsaturated Fatty Acid Supplement on Distinct Immune Functions of Goats,” Journal of Veterinary Medicine Series A, Vol. 5, No. 1, 2004, pp. 1-9.
[10] P. C. Calder, “n-3 Polyunsaturated Fatty Acids, Inflammation, and Inflammatory Diseases,” The American Journal of Clinical Nutrition, Vol. 83, No. 6, 2006, pp. 1505S-1519S.
[11] J. W. Fetterman Jr. and M. M. Zdanowicz, “Therapeutic Potential of n-3 Polyunsaturated Fatty Acids in Disease,” American Journal of Health System Pharmacy, Vol. 66, No. 13, 2009, pp. 1169-1179. doi:10.2146/ajhp080411
[12] C. L. Shen, J. Peterson, O. L. Tatum and D. M. Dunn, “Effect of Long-Chain n-3 Polyunsaturated Fatty Acid on Inflammation Mediators during Osteoblastogenesis,” Journal of Medicinal Food, Vol. 11, No. 1, 2008, pp. 105-110. doi:10.1089/jmf.2007.540
[13] D. S. Kelley, P. C. Taylor, G. J. Nelson, P. C. Schmidt, A. Ferretti, K. L. Erickson, R. Yu, R. K. Chandra and B. E. Mackey, “Docosahexaenoic Acid Ingestion Inhibits Natural Killer Cell Activity and Production of Inflammatory Mediators in Young Healthy Men,” Lipids, Vol. 34, No. 4, 1999, pp. 317-324.
[14] H. Seki, Y. Tani and M. Arita, “Omega-3 PUFA Derived Anti-Inflammatory Lipid Mediator Resolvin E1,” Prostaglandins & Other Lipid Mediators, Vol. 89, No. 4, 2009, pp. 126-130.
[15] N. G. Bazan, “Neuroprotectin D1-Mediated Anti-Inflammatory and Survival Signaling in Stroke, Retinal Degenerations, and Alzheimer’s Disease,” Journal of Lipid Reseach, Vol. 50, Suppl. 9, 2009, pp. S400-S405. doi:10.1194/jlr.R800068-JLR200
[16] H. D. Adkisson 4th, F. S. Risener Jr., P. P. Zarrinkar, M. D. Walla, W. W. Christie and R. E. Wuthier, “Unique Fatty Acid Composition of Normal Cartilage: Discovery of High Levels of n-9 Eicosatrienoic Acid and Low Levels of n-6 Polyunsaturated Fatty Acids,” FASEB Journal, Vol. 5, No. 3, 1991, pp. 344-353.
[17] T. Hamazaki, N. Suzuki, R. Widyowati, T. Miyahara, S. Kadota, H. Ochiai and K. Hamazaki, “The Depressive Effects of 5,8,11-Eicosatrienoic Acid (20:3n-9) on Osteoblasts,” Lipids, Vol. 44, No. 2, 2009, pp. 97-102. doi:10.1007/s11745-008-3252-8
[18] M. J. James, R. A. Gibson, M. A. Neumann and L. G. Cleland, “Effect of Dietary Supplementation with n-9 Eicosatrienoic Acid on Leukotriene B4 Synthesis in Rats: A Novel Approach to Inhibition of Eicosanoid Synthesis,” The Journal of Experimental Medicine, Vol. 178, No. 6, 1993, pp. 2261-2265.
[19] L. G. Cleland, R. A. Gibson, M. A. Neumann, T. Hamazaki, K. Akimoto and M. J. James, “Dietary (n-9) Eicosatrienoic Acid from a Cultured Fungus Inhibits Leukotriene B4 Synthesis in Rats and the Effect Is Modified by Dietary Linoleic Acid,” The Journal of Nutrition, Vol. 126, No. 6, 1996, pp. 1534-1540.
[20] S. Watanabe, M. Doshi, K. Akimoto, Y. Kiso and T. Hamazaki, “Suppression of Platelet-Activating Factor Generation and Modulation of Arachidonate Metabolism by Dietary Enrichment with (n-9) Eicosatrienoic Acid or Docosahexaenoic Acid in Mouse Peritoneal Cells,” Prostaglandins & Other Lipid Mediators, Vol. 66, No. 2, 2001, pp. 109-120. doi:10.1016/S0090-6980(01)00152-6
[21] M. Doshi, S. Watanabe, T. Niimoto, H. Kawashima, Y. Ishikura, Y. Kiso and T. Hamazaki, “Effect of Dietary Enrichment with n-3 Polyunsaturated Fatty Acids (PUFA) or n-9 PUFA on Arachidonate Metabolism in Vivo and Experimentally Induced Inflammation in Mice,” Biological & Pharmaceutical Bulletin, Vol. 27, No. 3, 2004, pp. 319-323. doi:10.1248/bpb.27.319
[22] Y. H. Jean, W. F. Chen, C. Y. Duh, S. Y. Huang, C. H. Hsu, C. S. Lin, C. S. Sung, I. M. Chen and Z. H. Wen, “Inducible Nitric Oxide Synthase and Cyclooxygenase-2 Participate in Anti-Inflammatory and Analgesic Effects of the Natural Marine Compound Lemnalol from Formosan Soft Coral Lemnalia cervicorni,” European Journal Pharmacology, Vol. 578, No. 3, 2008, pp. 323-331.
[23] Z. H. Wen, G. J. Wu, Y. C. Chang, J. J. Wang and C. S. Wong, “Dexamethasone Modulates the Development of Morphine Tolerance and Expression of Glutamate Transporters in Rats,” Neuroscience, Vol. 133, No. 3, 2005, pp. 807-817. doi:10.1016/j.neuroscience.2005.03.015
[24] D. Schneidman-Duhovny, Y. Inbar, R. Nussinov and H. J. Wolfson, “Patch Dock and Symm Dock: Servers for Rigid and Symmetric Docking,” Nucleic Acids Research, Vol. 33, Suppl. 2, 2005, pp. W363-W367. doi:10.1093/nar/gki481
[25] R. K. Saxena, V. Vallyathan and D. M. Lewis, “Evidence for Lipopolysaccharideinduced Differentiation of RAW264.7 Murine Macrophage Cell Line into Dendritic like Cells,” Journal of Bioscience, Vol. 28, No. 1, 2003, pp. 129-134. doi:10.1007/BF02970143
[26] H. M. Berman, J. Westbrook, Z. Feng, G. Gilliland, T. N. Bhat, H. Weissig, I. N. Shindyalov and P. E. Bourne, “The Protein Data Bank,” Nucleic Acids Research, Vol. 28, No. 1, 2000, pp. 235-242. doi:10.1093/nar/28.1.235
[27] P. J. Loll, D. Picot and R. M. Garavito, “The Structural Basis of Aspirin Activity Inferred from the Crystal Structure of Inactivated Prostaglandin H2 Synthase,” Nature Structural Biology, Vol. 2, No. 8, 1995, pp. 637-643. doi:10.1038/nsb0895-637
[28] R. G. Kurumbail, A. M. Stevens, J. K. Gierse, J. J. McDonald, R. A. Stegeman, J. Y. Pak, D. Gildehaus, J. M. Miyashiro, T. D. Penning, K. Seibert, P. C. Isakson and W. C. Stallings, “Structural Basis for Selective Inhibition of Cyclooxygenase-2 by Anti-Inflammatory Agents,” Nature, Vol. 384, No. 6610, 1996, pp. 644-648. doi:10.1038/384644a0
[29] A. Risser, D. Donovan, J. Heintzman and T. Page, “NSAID Prescribing Precautions,” American Family Physician, Vol. 80, No. 12, 2009, pp. 1371-1378.
[30] M. G. Malkowski, S. L. Ginell, W. L. Smith and R. M. Garavito, “The Productive Conformation of Arachidonic Acid Bound to Prostaglandin Synthase,” Science, Vol. 289, No. 5486, 2000, pp. 1933-1937. doi:10.1126/science.289.5486.1933
[31] J. R. Kiefer, J. L. Pawlitz, K. T. Moreland, R. A. Stegeman, W. F. Hood, J. K. Gierse, A. M. Stevens, D. C. Goodwin, S. W. Rowlinson, L. J. Marnett, W. C. Stallings and R. G. Kurumbail, “Structural Insights into the Stereochemistry of the Cyclooxygenase Reaction,” Nature, Vol. 405, No. 6782, 2000, pp. 97-101. doi:10.1038/35011103
[32] G. D. Basu, L. B. Pathangey, T. L. Tinder, S. J. Gendler and P. Mukherjee, “Mechanisms Underlying the Growth Inhibitory Effects of the Cyclo-Oxygenase-2 Inhibitor Celecoxib in Human Breast Cancer Cells,” Breast Cancer Research, Vol. 7, No. 4, 2005, pp. R422-435. doi:10.1186/bcr1019
[33] J. K. Srivastava, M. Pandey and S. Gupta, “Chamomile, a Novel and Selective COX-2 Inhibitor with Anti-Inflammatory Activity,” Life Sciences, Vol. 85, No. 19, 2009, pp. 663-669. doi:10.1016/j.lfs.2009.09.007
[34] A. Kadotani, Y. Tsuchiya, H. Hatakeyama, H. Katagiri and M. Kanzaki, “Different Impacts of Saturated and Unsaturated Free Fatty Acids on COX-2 Expression in C(2)C(12) Myotubes,” American Journal of Physiology Endocrinology and Metabolism, Vol. 297, No. 6, 2009, pp. E1291-E1303.
[35] C. D. Funk, “Prostaglandins and Leukotrienes: Advances in Eicosanoid Biology,” Science, Vol. 294, No. 5548, 2001, pp. 1871-1875. doi:10.1126/science.294.5548.1871
[36] Y. T. Oh, J. Y. Lee, J. Lee, H. Kim, K. S. Yoon, W. Choe and I. Kang, “Oleic Acid Reduces LipopolysaccharideInduced Expression of iNOS and COX-2 in BV2 Murine Microglial Cells: Possible Involvement of Reactive Oxygen Species, p38 MAPK, and IKK/NF-Kappa B Signaling Pathways,” Neuroscience Letters, Vol. 464, No. 2, 2009, pp. 93-97. doi:10.1016/j.neulet.2009.08.040.

comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.