{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T15:12:06Z","timestamp":1775142726503,"version":"3.50.1"},"reference-count":125,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T00:00:00Z","timestamp":1646265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/00100\/2020"],"award-info":[{"award-number":["UIDB\/00100\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UIDP\/CVT\/00276\/2020"],"award-info":[{"award-number":["UIDP\/CVT\/00276\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/SAUNUT\/30455\/2017"],"award-info":[{"award-number":["PTDC\/SAUNUT\/30455\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["2021.06108.BD"],"award-info":[{"award-number":["2021.06108.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Marine organisms are an important source of natural products with unique and diverse chemical structures that may hold the key for the development of novel drugs. Docosahexaenoic acid (DHA) is an omega-3 fatty acid marine natural product playing a crucial regulatory role in the resolution of inflammation and acting as a precursor for the biosynthesis of the anti-inflammatory specialized pro-resolving mediators (SPMs) resolvins, protectins, and maresins. These metabolites exert many beneficial actions including neuroprotection, anti-hypertension, or anti-tumorigenesis. As dysregulation of SPMs is associated with diseases of prolonged inflammation, the disclosure of their bioactivities may be correlated with anti-inflammatory and pro-resolving capabilities, offering new targets for drug design. The availability of these SPMs from natural resources is very low, but the evaluation of their pharmacological properties requires their access in larger amounts, as achieved by synthetic routes. In this report, the first review of the total organic syntheses carried out for resolvins, protectins, and maresins is presented. Recently, it was proposed that DHA-derived pro-resolving mediators play a key role in the treatment of COVID-19. In this work we also review the current evidence on the structures, biosynthesis, and functional and new-found roles of these novel lipid mediators of disease resolution.<\/jats:p>","DOI":"10.3390\/molecules27051677","type":"journal-article","created":{"date-parts":[[2022,3,3]],"date-time":"2022-03-03T09:24:53Z","timestamp":1646299493000},"page":"1677","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":91,"title":["Resolvins, Protectins, and Maresins: DHA-Derived Specialized Pro-Resolving Mediators, Biosynthetic Pathways, Synthetic Approaches, and Their Role in Inflammation"],"prefix":"10.3390","volume":"27","author":[{"given":"In\u00eas","family":"Ferreira","sequence":"first","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Faculdade de Ci\u00eancias, Universidade de Lisboa, Ed. C8, Piso 5, Campo Grande, 1749-016 Lisboa, Portugal"},{"name":"Division of Aquaculture, Upgrading and Bioprospecting, Portuguese Institute of the Sea and Atmosphere, Rua Alfredo Magalh\u00e3es Ramalho, 6, 1495-006 Lisboa, Portugal"}]},{"given":"Filipa","family":"Falcato","sequence":"additional","affiliation":[{"name":"Division of Aquaculture, Upgrading and Bioprospecting, Portuguese Institute of the Sea and Atmosphere, Rua Alfredo Magalh\u00e3es Ramalho, 6, 1495-006 Lisboa, Portugal"}]},{"given":"Narcisa","family":"Bandarra","sequence":"additional","affiliation":[{"name":"Division of Aquaculture, Upgrading and Bioprospecting, Portuguese Institute of the Sea and Atmosphere, Rua Alfredo Magalh\u00e3es Ramalho, 6, 1495-006 Lisboa, Portugal"},{"name":"Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3790-7952","authenticated-orcid":false,"given":"Am\u00e9lia P.","family":"Rauter","sequence":"additional","affiliation":[{"name":"Centro de Qu\u00edmica Estrutural, Institute of Molecular Sciences, Faculdade de Ci\u00eancias, Universidade de Lisboa, Ed. C8, Piso 5, Campo Grande, 1749-016 Lisboa, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.jchromb.2003.11.005","article-title":"Bioactive peptides from marine sources: Pharmacological properties and isolation procedures","volume":"803","author":"Aneiros","year":"2004","journal-title":"J. Chromatogr. B Anal. Technol. Biomed. Life Sci."},{"key":"ref_2","first-page":"159","article-title":"Secondary Metabolites of Marine Microbes: From Natural Products Chemistry to Chemical Ecology","volume":"9","author":"Petersen","year":"2020","journal-title":"YOUMARES"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1039\/C6NP00124F","article-title":"Marine natural products","volume":"34","author":"Blunt","year":"2017","journal-title":"Nat. Prod. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gallimore, W. (2017). Marine Metabolites: Oceans of Opportunity. Pharmacogn. Fundam. Appl. Strategy, 377\u2013400.","DOI":"10.1016\/B978-0-12-802104-0.00018-4"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Barzkar, N., Jahromi, S.T., Poorsaheli, H.B., and Vianello, F. (2019). Metabolites from marine microorganisms, micro, and macroalgae: Immense scope for pharmacology. Mar. Drugs, 17.","DOI":"10.3390\/md17080464"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1111\/1541-4337.12136","article-title":"Marine Bioactive Compounds and Their Health Benefits: A Review","volume":"14","author":"Hamed","year":"2015","journal-title":"Compr. Rev. Food Sci. Food Saf."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6530","DOI":"10.1073\/pnas.1304321110","article-title":"Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis","volume":"110","author":"Zhang","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s11883-004-0087-5","article-title":"Omega-3 fatty acids and inflammation","volume":"6","author":"Mori","year":"2004","journal-title":"Curr. Atheroscler. Rep."},{"key":"ref_9","first-page":"831","article-title":"Benefits of omega-3 fatty acid dietary supplementation on health-related quality of life in patients with meibomian gland dysfunction","volume":"8","author":"Luxan","year":"2014","journal-title":"Clin. Ophthalmol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Innes, J.K., and Calder, P.C. (2020). Marine omega-3 (N-3) fatty acids for cardiovascular health: An update for 2020. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21041362"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Avallone, R., Vitale, G., and Bertolotti, M. (2019). Omega-3 fatty acids and neurodegenerative diseases: New evidence in clinical trials. Int. J. Mol. Sci., 20.","DOI":"10.20944\/preprints201907.0289.v1"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1017\/S0007114512001456","article-title":"Dietary sources of omega 3 fatty acids: Public health risks and benefits","volume":"107","author":"Tur","year":"2012","journal-title":"Br. J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"355","DOI":"10.3390\/nu2030355","article-title":"Omega-3 fatty acids and inflammatory processes","volume":"2","author":"Calder","year":"2010","journal-title":"Nutrients"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2617","DOI":"10.1080\/10408398.2017.1338245","article-title":"Dietary DHA, bioaccessibility, and neurobehavioral development in children","volume":"58","author":"Cardoso","year":"2018","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1365-2621.1997.tb04364.x","article-title":"Seasonal changes in lipid composition of sardine (Sardina pilchardus)","volume":"62","author":"Bandarra","year":"1997","journal-title":"J. Food Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.biochi.2020.09.022","article-title":"The chemical composition and lipid profile of the chub mackerel (Scomber colias) show a strong seasonal dependence: Contribution to a nutritional evaluation","volume":"178","author":"Ferreira","year":"2020","journal-title":"Biochimie"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.3945\/ajcn.2010.29457","article-title":"Dietary intake and status of n-3 polyunsaturated fatty acids in a population of fish-eating and non-fish-eating meat-eaters, vegetarians, and vegans and the precursor-product ratio of \u03b1-linolenic acid to long-chain n-3 polyunsaturated fatty acids: Results","volume":"92","author":"Welch","year":"2010","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1017\/S0954422416000184","article-title":"Dietary DHA and health: Cognitive function ageing","volume":"29","author":"Cardoso","year":"2016","journal-title":"Nutr. Res. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000448262","article-title":"Docosahexaenoic acid","volume":"69","author":"Calder","year":"2016","journal-title":"Ann. Nutr. Metab."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.3390\/nu5072777","article-title":"The relationship of docosahexaenoic acid (DHA) with learning and behavior in healthy children: A review","volume":"5","author":"Kuratko","year":"2013","journal-title":"Nutrients"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1080\/10408398.2019.1573800","article-title":"The role of marine omega-3 in human neurodevelopment, including Autism Spectrum Disorders and Attention-Deficit\/Hyperactivity Disorder\u2013a review","volume":"60","author":"Martins","year":"2020","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_22","first-page":"1","article-title":"Enhancing Omega-3 Long-Chain Polyunsaturated Human Consumption","volume":"743","author":"Nguyen","year":"2019","journal-title":"Nutrients"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/mnfr.201900824","article-title":"Immuno-Resolving Ability of Resolvins, Protectins, and Maresins Derived from Omega-3 Fatty Acids in Metabolic Syndrome","volume":"64","author":"Kwon","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.biochi.2017.01.002","article-title":"Bioactive metabolites of docosahexaenoic acid","volume":"136","author":"Kuda","year":"2017","journal-title":"Biochimie"},{"key":"ref_25","first-page":"1","article-title":"Resolution-Based Therapies: The Potential of Lipoxins to Treat Human Diseases","volume":"12","author":"Prieto","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ejphar.2015.11.001","article-title":"DHA- and EPA-derived resolvins, protectins, and maresins in airway inflammation","volume":"785","author":"Duvall","year":"2016","journal-title":"Eur. J. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1172\/JCI97943","article-title":"Resolvins in inflammation: Emergence of the pro-resolving superfamily of mediators","volume":"128","author":"Serhan","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1843","DOI":"10.1016\/j.tetlet.2015.02.080","article-title":"Stereoselective synthesis of maresin 1","volume":"56","author":"Tungen","year":"2015","journal-title":"Tetrahedron Lett."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5922","DOI":"10.1021\/cr100396c","article-title":"Resolvins and protectins in inflammation resolution","volume":"111","author":"Serhan","year":"2011","journal-title":"Chem. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"17949","DOI":"10.1073\/pnas.0802572105","article-title":"Tonic inhibition of chemotaxis in human plasma","volume":"105","author":"Malawista","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.immuni.2016.02.026","article-title":"Phagocytosis: An Immunobiologic Process","volume":"44","author":"Gordon","year":"2016","journal-title":"Immunity"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.coph.2013.05.012","article-title":"Resolution phase lipid mediators of inflammation: Agonists of resolution","volume":"13","author":"Serhan","year":"2013","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1096\/fj.201601222R","article-title":"Treating inflammation and infection in the 21st century: New hints from decoding resolution mediators and mechanisms","volume":"31","author":"Serhan","year":"2017","journal-title":"FASEB J."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1038\/nature13479","article-title":"Pro-resolving lipid mediators are leads for resolution physiology","volume":"510","author":"Serhan","year":"2014","journal-title":"Nature"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"612","DOI":"10.3389\/fphar.2020.00612","article-title":"Role of Resolvins in the Inflammatory Resolution of Neurological Diseases","volume":"11","author":"Li","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1084\/jem.20020760","article-title":"Resolvins: A family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals","volume":"196","author":"Serhan","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1096\/fj.11-201442","article-title":"Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain","volume":"26","author":"Serhan","year":"2012","journal-title":"FASEB J."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8491","DOI":"10.1073\/pnas.0402531101","article-title":"Neuroprotectin D1: A docosahexaenoic acid-derived docosatriene protects human retinal pigment epithelial cells from oxidative stress","volume":"101","author":"Mukherjee","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1042\/EBC20200018","article-title":"Specialized pro-resolving mediator network: An update on production and actions","volume":"64","author":"Chiang","year":"2020","journal-title":"Essays Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"455","DOI":"10.4062\/biomolther.2021.094","article-title":"Specialized proresolving mediators for therapeutic interventions targeting metabolic and inflammatory disorders","volume":"29","author":"Han","year":"2021","journal-title":"Biomol. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2789","DOI":"10.3389\/fmicb.2020.587725","article-title":"Clostridium butyricum MIYAIRI 588-Induced Protectin D1 Has an Anti-inflammatory Effect on Antibiotic-Induced Intestinal Disorder","volume":"11","author":"Ariyoshi","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"5902","DOI":"10.4049\/jimmunol.177.9.5902","article-title":"Resolvin D Series and Protectin D1 Mitigate Acute Kidney Injury","volume":"177","author":"Duffield","year":"2006","journal-title":"J. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1111\/j.1476-5381.2009.00290.x","article-title":"Resolvins and protectins: Mediating solutions to inflammation","volume":"158","author":"Kohli","year":"2009","journal-title":"Br. J. Pharmacol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.1096\/fj.12-225615","article-title":"D-series resolvin attenuates vascular smooth muscle cell activation and neointimal hyperplasia following vascular injury","volume":"27","author":"Miyahara","year":"2013","journal-title":"FASEB J."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"155","DOI":"10.3233\/JAD-121735","article-title":"1\u03b1,25-dihydroxyvitamin D3 and resolvin D1 retune the balance between amyloid-\u03b2 phagocytosis and inflammation in Alzheimer\u2019s disease patients","volume":"34","author":"Mizwicki","year":"2013","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/nm.2123","article-title":"Resolvins RvE1 and RvD1 attenuate inflammatory pain via central and peripheral actions","volume":"16","author":"Xu","year":"2010","journal-title":"Nat. Med."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1111\/j.1476-5381.2011.01568.x","article-title":"17(R)-resolvin D1 specifically inhibits transient receptor potential ion channel vanilloid 3 leading to peripheral antinociception","volume":"165","author":"Bang","year":"2012","journal-title":"Br. J. Pharmacol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"a016311","DOI":"10.1101\/cshperspect.a016311","article-title":"Lipid mediators in the resolution of inflammation","volume":"7","author":"Serhan","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/j.1476-5381.2011.01345.x","article-title":"The precursor of resolvin D series and aspirin-triggered resolvin D1 display anti-hyperalgesic properties in adjuvant-induced arthritis in rats","volume":"164","author":"Dutra","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.neuropharm.2014.05.043","article-title":"Effects of D-series resolvins on behavioral and neurochemical changes in a fibromyalgia-like model in mice","volume":"86","author":"Klein","year":"2014","journal-title":"Neuropharmacology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3564","DOI":"10.1096\/fj.13-230276","article-title":"Aspirin-triggered resolvin D1 prevents surgery-induced cognitive decline","volume":"27","author":"Terrando","year":"2013","journal-title":"FASEB J."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"43807","DOI":"10.1074\/jbc.M305841200","article-title":"Novel Docosanoids Inhibit Brain Ischemia-Reperfusion-mediated Leukocyte Infiltration and Pro-inflammatory Gene Expression","volume":"278","author":"Marcheselli","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1038\/ni1392","article-title":"Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression","volume":"7","author":"Ariel","year":"2006","journal-title":"Nat. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1038\/nature05877","article-title":"Resolvin E1 and protectin D1 activate inflammation-resolution programmes","volume":"447","author":"Schwab","year":"2007","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"43079","DOI":"10.1074\/jbc.M509796200","article-title":"The docosatriene protectin D1 is produced by TH2 skewing promotes human T cell via lipid raft clustering","volume":"280","author":"Ariel","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"14677","DOI":"10.1074\/jbc.M300218200","article-title":"Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells: Autacoids in anti-inflammation","volume":"278","author":"Hong","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"496","DOI":"10.4049\/jimmunol.178.1.496","article-title":"Protectin D1 Is Generated in Asthma and Dampens Airway Inflammation and Hyperresponsiveness","volume":"178","author":"Levy","year":"2007","journal-title":"J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.bbrc.2015.03.109","article-title":"Resolvin D2 recovers neural injury by suppressing inflammatory mediators expression in lipopolysaccharide-induced Parkinson\u2019s disease rat model","volume":"460","author":"Tian","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.chembiol.2012.11.010","article-title":"Resolvin D3 and aspirin-triggered resolvin D3 are potent immunoresolvents","volume":"20","author":"Dalli","year":"2013","journal-title":"Chem. Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"18972","DOI":"10.1038\/srep18972","article-title":"Resolvin D4 stereoassignment and its novel actions in host protection and bacterial clearance","volume":"6","author":"Winkler","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"e21775","DOI":"10.1096\/fj.202100686R","article-title":"Elucidating the structure and functions of Resolvin D6 isomers on nerve regeneration with a distinctive trigeminal transcriptome","volume":"35","author":"Pham","year":"2021","journal-title":"FASEB J."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Hwang, S.M., Chung, G., Kim, Y.H., and Park, C.K. (2019). The role of maresins in inflammatory pain: Function of macrophages in wound regeneration. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20235849"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"11731","DOI":"10.1523\/JNEUROSCI.1395-17.2017","article-title":"Maresin 1 promotes inflammatory resolution, neuroprotection, and functional neurological recovery after spinal cord injury","volume":"37","author":"Gronert","year":"2017","journal-title":"J. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.tetlet.2014.11.082","article-title":"First total synthesis of the macrophage derived anti-inflammatory and pro-resolving lipid mediator Maresin 2","volume":"56","author":"Rodriguez","year":"2015","journal-title":"Tetrahedron Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"14744","DOI":"10.1074\/jbc.M809014200","article-title":"Biogenic synthesis, purification, and chemical characterization of anti-inflammatory resolvins derived from docosapentaenoic acid (DPAn-6)","volume":"284","author":"Dangi","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/nature11042","article-title":"Infection regulates pro-resolving mediators that lower antibiotic requirements","volume":"484","author":"Oh","year":"2012","journal-title":"Nature"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1172\/JCI42545","article-title":"Pro-resolving actions and stereoselective biosynthesis of 18S E-series resolvins in human leukocytes and murine inflammation","volume":"121","author":"Oh","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jasms.2006.09.002","article-title":"Resolvin D1, Protectin D1, and related docosahexaenoic acid-derived products: Analysis via electrospray\/low energy tandem mass spectrometry based on spectra and fragmentation mechanisms","volume":"18","author":"Hong","year":"2007","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/j.1750-3639.2005.tb00513.x","article-title":"Neuroprotectin D1 (NPD1): A DHA-derived mediator that protects brain and retina against cell injury-induced oxidative stress","volume":"15","author":"Bazan","year":"2005","journal-title":"Brain Pathol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.mam.2017.03.005","article-title":"Structural elucidation and physiologic functions of specialized pro-resolving mediators and their receptors","volume":"58","author":"Chiang","year":"2017","journal-title":"Mol. Asp. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s41581-021-00454-y","article-title":"Pro-resolving lipid mediators: Regulators of inflammation, metabolism and kidney function","volume":"17","author":"Brennan","year":"2021","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.taap.2014.03.017","article-title":"Aspirin-triggered resolvin D1 down-regulates inflammatory responses and protects against endotoxin-induced acute kidney injury","volume":"277","author":"Chen","year":"2014","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3389\/fphys.2020.00285","article-title":"Resolvin D1 Protects Against Ischemia\/Reperfusion-Induced Acute Kidney Injury by Increasing Treg Percentages via the ALX\/FPR2 Pathway","volume":"11","author":"Luan","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1002\/path.4050","article-title":"Resolvins E1 and D1 inhibit interstitial fibrosis in the obstructed kidney via inhibition of local fibroblast proliferation","volume":"228","author":"Qu","year":"2012","journal-title":"J. Pathol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1084\/jem.20170681","article-title":"Resolvins suppress tumor growth and enhance cancer therapy","volume":"215","author":"Sulciner","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.plefa.2018.11.013","article-title":"Combined administration of docosahexaenoic acid and thyroid hormone synergistically enhances rat liver levels of resolvins RvD1 and RvD2","volume":"140","author":"Videla","year":"2019","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.3389\/fphar.2018.01582","article-title":"The protectin family of specialized pro-resolving mediators: Potent immunoresolvents enabling innovative approaches to target obesity and diabetes","volume":"9","author":"Hansen","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"6292","DOI":"10.1073\/pnas.1804000116","article-title":"Aspirin-triggered proresolving mediators stimulate resolution in cancer","volume":"116","author":"Gilligan","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9323","DOI":"10.1074\/jbc.M609212200","article-title":"Resolvin D1 and its aspirin-triggered 17R epimer: Stereochemical assignments, anti-inflammatory properties, and enzymatic inactivation","volume":"282","author":"Sun","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"6990","DOI":"10.1016\/j.tetlet.2012.10.059","article-title":"Total synthesis of Resolvin D1, a potent anti-inflammatory lipid mediator","volume":"53","author":"Rodriguez","year":"2012","journal-title":"Tetrahedron Lett."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1039\/C8OB03128B","article-title":"Stereocontrolled synthesis of resolvin D1","volume":"17","author":"Morita","year":"2019","journal-title":"Org. Biomol. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1039\/c39730000151","article-title":"One- step Conversion of Carbonyl Compounds into Acetylenes By ERNEST","volume":"5","author":"Colvin","year":"1973","journal-title":"Chem. Commun."},{"key":"ref_83","first-page":"107","article-title":"Extension of the colvin rearrangement using trimethylsilyldiazomethane. A new synthesis of alkynes","volume":"1994","year":"1993","journal-title":"Synlett"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1021\/ol061202o","article-title":"A convenient and genuine equivalent to HZrCp2Cl generated in situ from ZrCp2Cl2-DIBAL-H","volume":"8","author":"Huang","year":"2006","journal-title":"Org. Lett."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8717","DOI":"10.1016\/j.tetlet.2004.09.129","article-title":"First total synthesis of 7(S),16(R),17(S)-Resolvin D2, a potent anti-inflammatory lipid mediator","volume":"45","author":"Spur","year":"2004","journal-title":"Tetrahedron Lett."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"2762","DOI":"10.3762\/bjoc.9.310","article-title":"Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin","volume":"9","author":"Li","year":"2013","journal-title":"Beilstein J. Org. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5161","DOI":"10.1016\/S0040-4039(99)00956-9","article-title":"Selective oxidation of primary silyl ethers and its application to the synthesis of natural products","volume":"40","author":"Nomen","year":"1999","journal-title":"Tetrahedron Lett."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1021\/acs.orglett.0c00089","article-title":"A Modular, Enantioselective Synthesis of Resolvins D3, E1, and Hybrids","volume":"22","author":"Urbitsch","year":"2020","journal-title":"Org. Lett."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1039\/a608187h","article-title":"\u03c9-Halogeno polyenals: Preparation and application to a one-pot synthesis of polyenals from carbonyl compounds","volume":"1","author":"Soullez","year":"1997","journal-title":"J. Chem. Soc. Perkin Trans."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/JLB.3MI0617-254R","article-title":"Frontline Science: Structural insights into Resolvin D4 actions and further metabolites via a new total organic synthesis and validation","volume":"103","author":"Winkler","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3623","DOI":"10.1016\/j.tetlet.2005.03.175","article-title":"First total synthesis of 7(S), 17(S)-Resolvin D5, a potent anti-inflammatory docosanoid","volume":"46","author":"Spur","year":"2005","journal-title":"Tetrahedron Lett."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"7408","DOI":"10.1021\/ja00283a046","article-title":"Simple and selective method for aldehydes (RCHO). fwdarw. (E)-haloalkenes (RCH:CHX) conversion by means of a haloform-chromous chloride system","volume":"108","author":"Takai","year":"1986","journal-title":"J. Am. Chem. Soc."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1021\/acs.joc.6b02870","article-title":"Total Synthesis of Resolvin D5","volume":"82","author":"Ogawa","year":"2017","journal-title":"J. Org. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.tetlet.2011.11.003","article-title":"First total synthesis of the anti-inflammatory lipid mediator Resolvin D6","volume":"53","author":"Rodriguez","year":"2012","journal-title":"Tetrahedron Lett."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1055\/s-0037-1611826","article-title":"Synthesis of Resolvin D6 and the Silyl Ether of the Resolvin E2 Methyl Ester via trans -Enynyl Alcohols","volume":"30","author":"Morita","year":"2019","journal-title":"Synlett"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"4706","DOI":"10.1021\/ol402017x","article-title":"Convergent access to bis-spiroacetals through a sila-Stetter-ketalization cascade","volume":"15","author":"Beniazza","year":"2013","journal-title":"Org. Lett."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"8738","DOI":"10.1021\/ja971570a","article-title":"The first asymmetric transfer hydrogenation of acetylenic ketones using chiral Ru (II) catalysts and 2-propanol as the hydrogen donor. 9 This method allows highly selective reduction of structurally diverse acetylenic ketones to propargylic alcohols of","volume":"119","author":"Matsumura","year":"1997","journal-title":"J. Am. Chem. Soc."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1021\/np4009865","article-title":"V Total Synthesis of the Lipid Mediator PD1","volume":"77","author":"Aursnes","year":"2015","journal-title":"J. Nat. Prod."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"12390","DOI":"10.1074\/jbc.R117.783076","article-title":"Molecular mechanisms of signaling via the docosanoid neuroprotectin D1 for cellular homeostasis and neuroprotection","volume":"292","author":"Asatryan","year":"2017","journal-title":"J. Biol. Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.plefa.2009.10.010","article-title":"Neuroprotectin D1\/protectin D1 stereoselective and specific binding with human retinal pigment epithelial cells and neutrophils","volume":"82","author":"Marcheselli","year":"2010","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1194\/jlr.R001131","article-title":"Rescue and repair during photoreceptor cell renewal mediated by docosahexaenoic acid-derived neuroprotectin D1","volume":"51","author":"Bazan","year":"2010","journal-title":"J. Lipid Res."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.plipres.2018.11.001","article-title":"Emerging role of 12\/15-Lipoxygenase (ALOX15) in human pathologies","volume":"73","author":"Singh","year":"2019","journal-title":"Prog. Lipid Res."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1946","DOI":"10.1096\/fj.08-125674","article-title":"Obesity-induced insulin resistance and hepatic steatosis are alleviated by \u03c9-3 fatty acids: A role for resolvins and protectins","volume":"23","author":"Horrillo","year":"2009","journal-title":"FASEB J."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.mam.2017.03.004","article-title":"Pro-resolving actions of SPM in adipose tissue biology","volume":"58","author":"Rius","year":"2017","journal-title":"Mol. Asp. Med."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3001","DOI":"10.1016\/j.tetlet.2011.03.152","article-title":"Total synthesis of the antiinflammatory and proresolving protectin D1","volume":"52","author":"Ogawa","year":"2011","journal-title":"Tetrahedron Lett."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/j.tetlet.2012.01.032","article-title":"Stereocontrolled total synthesis of Neuroprotectin D1\/Protectin D1 and its aspirin-triggered stereoisomer","volume":"53","author":"Petasis","year":"2012","journal-title":"Tetrahedron Lett."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"6011","DOI":"10.1016\/j.tetlet.2014.09.007","article-title":"Total synthesis of the potent anti-inflammatory lipid mediator Protectin D1","volume":"55","author":"Rodriguez","year":"2014","journal-title":"Tetrahedron Lett."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"9961","DOI":"10.1021\/acs.jmedchem.9b01463","article-title":"Rapid Metabolization of Protectin D1 by \u03b2-Oxidation of Its Polar Head Chain","volume":"62","author":"Balas","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"M\u00fcller, S., Liepold, B., Gerald, J., and Roth, H.J.B. (1996). An Improved One-pot Procedure for the Synthesis of Alkynes from Aldehydes. Synlett, 521\u2013522.","DOI":"10.1055\/s-1996-5474"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"2879","DOI":"10.1002\/chem.201304526","article-title":"A versatile and stereocontrolled total synthesis of dihydroxylated docosatrienes containing a conjugated E,E,Z-triene","volume":"20","author":"Dayaker","year":"2014","journal-title":"Chem. Eur. J."},{"key":"ref_111","first-page":"7442","article-title":"Maresins: Anti-inflammatory pro-resolving mediators with therapeutic potential","volume":"24","author":"Li","year":"2020","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/asia.201000494","article-title":"Total synthesis and bioactivities of two proposed structures of maresin","volume":"6","author":"Sasaki","year":"2011","journal-title":"Chem. Asian J."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"4169","DOI":"10.1016\/j.tetlet.2012.05.143","article-title":"Total synthesis of the macrophage derived anti-inflammatory lipid mediator Maresin 1","volume":"53","author":"Rodriguez","year":"2012","journal-title":"Tetrahedron Lett."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"7277","DOI":"10.1021\/ja00019a027","article-title":"A Useful 12-I-5 Triacetoxyperiodinane (the Dess-Martin Periodinane) for the Selective Oxidation of Primary or Secondary Alcohols and a Variety of Related 12-I-5 Species","volume":"113","author":"Dess","year":"1991","journal-title":"J. Am. Chem. Soc."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.1016\/j.chembiol.2014.06.010","article-title":"Maresin-like lipid mediators are produced by leukocytes and platelets and rescue reparative function of diabetes-impaired macrophages","volume":"21","author":"Hong","year":"2014","journal-title":"Chem. Biol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1055\/s-0037-1612011","article-title":"Stereoselective Synthesis of Maresin-Like Lipid Mediators","volume":"30","author":"Hong","year":"2019","journal-title":"Synlett"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1136\/bmjnph-2020-000085","article-title":"Nutrition, immunity and COVID-19","volume":"3","author":"Calder","year":"2020","journal-title":"BMJ Nutr. Prev. Health"},{"key":"ref_118","first-page":"E304","article-title":"Determine the most common clinical symptoms in COVID-19 patients: A systematic review and meta-analysis","volume":"61","author":"Alimohamadi","year":"2020","journal-title":"J. Prev. Med. Hyg."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/s41418-020-00720-9","article-title":"COVID-19 vaccines: Where we stand and challenges ahead","volume":"28","author":"Forni","year":"2021","journal-title":"Cell Death Differ."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"100943","DOI":"10.1016\/j.mam.2021.100943","article-title":"The need for precision nutrition, genetic variation and resolution in Covid-19 patients","volume":"77","author":"Simopoulos","year":"2021","journal-title":"Mol. Asp. Med."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"110900","DOI":"10.1016\/j.nut.2020.110900","article-title":"Parenteral fish oil: An adjuvant pharmacotherapy for coronavirus disease 2019?","volume":"81","author":"Torrinhas","year":"2021","journal-title":"Nutrition"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.arcmed.2020.03.004","article-title":"Can Bioactive Lipids Inactivate Coronavirus (COVID-19)?","volume":"51","author":"Das","year":"2020","journal-title":"Arch. Med. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.freeradbiomed.2020.07.005","article-title":"Potential benefits and risks of omega-3 fatty acids supplementation to patients with COVID-19","volume":"156","author":"Rogero","year":"2020","journal-title":"Free Radic. Biol. Med. J."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"9843","DOI":"10.1096\/fj.202001451","article-title":"COVID-19\u2014Associated dyslipidemia: Implications for mechanism of impaired resolution and novel therapeutic approaches","volume":"34","author":"Sorokin","year":"2020","journal-title":"FASEB J."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"12787","DOI":"10.1038\/s41598-021-92293-x","article-title":"ELV-N32 and RvD6 isomer decrease pro-inflammatory cytokines, senescence programming, ACE2 and SARS-CoV-2-spike protein RBD binding in injured cornea","volume":"11","author":"Pham","year":"2021","journal-title":"Sci. Rep."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/5\/1677\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:31:38Z","timestamp":1760135498000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/5\/1677"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,3]]},"references-count":125,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["molecules27051677"],"URL":"https:\/\/doi.org\/10.3390\/molecules27051677","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,3]]}}}