Protectins and maresins: new pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome

Serhan, Charles N.; Dalli, Jesmond; Colas, Romain A.; Winkler, Jeremy W.; Chiang, Nan

doi:10.1016/j.bbalip.2014.08.006

Cited by 492Fatty Acid Research and HealthInflammatory mediators and NSAID effectsEicosanoids and Hypertension Pharmacology

Protectins and maresins: new pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome

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Serhan, Charles N., Dalli, Jesmond, Colas, Romain A., Winkler, Jeremy W., Chiang, Nan·2015·Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids

DOI 10.1016/j.bbalip.2014.08.006PMC PMC4324013

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Abstract

Acute inflammatory responses are protective, yet without timely resolution can lead to chronic inflammation and organ fibrosis. A systems approach to investigate self-limited (self-resolving) inflammatory exudates in mice and structural elucidation uncovered novel resolution phase mediators in vivo that stimulate endogenous resolution mechanisms in inflammation. Resolving inflammatory exudates and human leukocytes utilize DHA and other n-3 EFA to produce three structurally distinct families of potent di- and trihydroxy-containing products, with several stereospecific potent mediators in each family. Given their potent and stereoselective picogram actions, specific members of these new families of mediators from the DHA metabolome were named D-series resolvins (Resolvin D1 to Resolvin D6), protectins (including protectin D1-neuroprotectin D1), and maresins (MaR1 and MaR2). In this review, we focus on a) biosynthesis of protectins and maresins as anti-inflammatory-pro-resolving mediators; b) their complete stereochemical assignments and actions in vivo in disease models. Each pathway involves the biosynthesis of epoxide-containing intermediates produced from hydroperoxy-containing precursors from human leukocytes and within exudates. Also, aspirin triggers an endogenous DHA metabolome that biosynthesizes potent products in inflammatory exudates and human leukocytes, namely aspirin-triggered Neuroprotectin D1/Protectin D1 [AT-(NPD1/PD1)]. Identification and structural elucidation of these new families of bioactive mediators in resolution has opened the possibility of diverse patho-physiologic actions in several processes including infection, inflammatory pain, tissue regeneration, neuroprotection-neurodegenerative disorders, wound healing, and others. This article is part of a Special Issue entitled "Oxygenated metabolism of PUFA: analysis and biological relevance".

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Aspirin enhances the neuroprotective bioactivity of the pathway leading to NPD1 formation.
“NPD1 is highlighted here as a neuroprotective mediator in ischemic stroke, as defined by cellular and molecular targets, and demonstrated that the pathway that leads to its formation was enhanced in its neuroprotective bioactivity by the presence of aspirin (Marcheselli et al., 2003) by aspirin-triggered NPD1 (Bazan et al., 2012; Serhan et al., 2015; Serhan and Petasis, 2011).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Serhan et al., 2015
NPD1 is a neuroprotective mediator in ischemic stroke, as defined by cellular and molecular targets.
“NPD1 is highlighted here as a neuroprotective mediator in ischemic stroke, as defined by cellular and molecular targets, and demonstrated that the pathway that leads to its formation was enhanced in its neuroprotective bioactivity by the presence of aspirin (Marcheselli et al., 2003) by aspirin-triggered NPD1 (Bazan et al., 2012; Serhan et al., 2015; Serhan and Petasis, 2011).”
From Docosanoids and elovanoids from omega-3 fatty acids are pro-homeostatic modulators of inflammatory responses, cell damage and neuroprotection (2018) · cites this paper as Serhan et al., 2015

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Authors: Serhan, C. N., Dalli, J., Colas, R. A., Winkler, J. W., & Chiang, N.
Affiliations: Brigham and Women's Hospital (US)
Corresponding author: Serhan, Charles N.
ORCID: Serhan, Charles N.
Dalli, Jesmond
Chiang, Nan
Venue: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
Publisher: Elsevier BV
Published: 2015-04
Volume: 1851
Issue: 4
Pages: 397-413
ISSN: 1388-1981 (ISSN-L)
DOI: 10.1016/j.bbalip.2014.08.006
PMC: PMC4324013
OpenAlex: W2049424212
Cited by: 492
References: 166
Citations by year: 2026: 19 · 2025: 32 · 2024: 35 · 2023: 38 · 2022: 52 · 2021: 56 · 2020: 55 · 2019: 34 · 2018: 57 · 2017: 52 · 2016: 32 · 2015: 28 · 2014: 2
FWCI: 4.33
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Mérieux Foundation (R01GM038765)
NIH (P01GM095467)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
Keywords: protectins, maresins, resolvins, neuroprotectin D1, protectin D1, omega-3 fatty acids, acute inflammation, inflammation resolution, epoxide intermediate, hydroperoxides, leukocytes, aspirin, neuroprotection, wound healing, inflammatory pain
MeSH terms: Animals, Anti-Inflammatory Agents, Aspirin, Docosahexaenoic Acids, Humans, Inflammation, Structure-Activity Relationship, Molecular Structure, Signal Transduction, Metabolome, Lipoxygenases

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Protectins and maresins: new pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome

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