Resolvins, Protectins, and Maresins: DHA-Derived Specialized Pro-Resolving Mediators, Biosynthetic Pathways, Synthetic Approaches, and Their Role in Inflammation
Open accessAbstract
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.
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Oxidation of ω-3 PUFAs like DHA or EPA by LOX or CYP450 leads to generation of protectins, resolvins and maresins.
“Oxidation of ω-3 PUFAs like docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) by LOX or CYP450 leads to the generation of protectins, resolvins and maresins.416”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [416]
Section 2 identifies DHA-derived protectins, D-series resolvins and maresins, and EPA-derived E-series resolvins. Sections 3.1, 4.1 and 5.1 describe LOX-dependent biosynthesis of the named mediator families. Section 5.3 mentions cytochrome P450 in the biosynthesis of maresin-like mediators, but does not establish it as a pathway for generating all three families; the claim also leaves unclear that protectins and maresins are described as DHA-derived, not EPA-derived. (LLM, conf=0.86)
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- [22]Nguyen Q.V. Malau-Aduli B.S. John C. Nichols P.D. Malau-Aduli E.O. Enhancing Omega-3 Long-Chain Polyunsaturated Human Consumption Nutrients 2019 743 1 23 PMC6520953 30934976
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“Oxidation of ω-3 PUFAs like docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) by LOX or CYP450 leads to the generation of protectins, resolvins and maresins.(416) LXs, protectins, resolvins and maresins are SPMs generated in human tissues and play critical role in inflammation resolution.”
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- Authors
- Ferreira, I., Falcato, F., Bandarra, N., & Rauter, A. P.
- Affiliations
- University of Lisbon (PT)
- Portuguese Sea and Atmosphere Institute (PT)
- Universidade do Porto (PT)
- Corresponding author
- Bandarra, Narcisa
- Rauter, Amélia P.
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2022-03-03
- Volume
- 27
- Issue
- 5
- Pages
- 1677
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC8912121
- OpenAlex
- W4214905414
- Cited by
- 120
- References
- 128
- Citations by year
- 2026: 39 · 2025: 32 · 2024: 20 · 2023: 22 · 2022: 7
- FWCI
- 2.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Fundação para a Ciência e Tecnologia (UIDB/00100/2020, UIDP/CVT/00276/2020, PTDC/SAUNUT/30455/2017, 2021.06108.BD)
- 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 › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- resolvins, protectins, maresins, specialized pro-resolving mediators, docosahexaenoic acid, omega-3 fatty acids, biosynthesis, inflammation resolution, lipid mediators, marine natural products, COVID-19 pandemic, drug design
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Anti-Inflammatory Agents, Docosahexaenoic Acids, Humans, Inflammation, Drug Design
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