Specialized pro-resolving lipid mediator pathway (Resolvins pathway) (SPM/resolvin pathway)

The **lipid mediators/resolvins pathway** refers to a family of endogenous metabolic cascades that generate specialized pro-resolving lipid mediators (SPMs), including resolvins, protectins, maresins, and lipoxins. These molecules are derived from omega−3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and n−3 docosapentaenoic acid through enzymatic actions involving cyclooxygenases, lipoxygenases, and cytochrome P450 monooxygenases. Resolvins actively orchestrate the resolution phase of inflammation by counterregulating classic pro-inflammatory signals—promoting clearance of apoptotic cells by macrophages ("efferocytosis"), inhibiting neutrophil infiltration, downregulating cytokine production such as IL‑6 and CCL5 via MAPK/NF‑κB pathways, reducing leukocyte adhesion molecule expression, attenuating dendritic cell activation, modulating microRNA expression patterns, and stimulating tissue repair processes. This is not a single molecular target but rather an interconnected network/pathway involving multiple enzymes (such as ALOX5/ALOX15), receptors for individual SPMs (some G protein-coupled receptors have been proposed but remain incompletely validated in humans), downstream intracellular signaling cascades, and their bioactive metabolites. The overall function is anti-inflammatory/pro-resolution rather than immunosuppressive. Dysregulation or insufficient activity within this system has been implicated in chronic inflammatory diseases—including cardiovascular disorders, autoimmune conditions like rheumatoid arthritis or lupus, neurodegenerative diseases such as Alzheimer's disease, metabolic syndrome/diabetes, asthma/allergy, psoriasis, among others. While there is significant interest in developing stable synthetic analogs or mimetics for therapeutic use—especially for treating chronic inflammatory conditions—no drugs currently approved specifically target this entire biosynthetic/signaling axis. Instead research focuses on individual SPM molecules/receptors. Because "lipid mediators/resolvins pathway" describes a broad biochemical process rather than a discrete druggable entity like an enzyme or receptor subunit—and because it encompasses many different molecular species—it should not be considered a canonical therapeutic target per se. For structured data purposes it is best classified under "Other" with respect to molecular classification; more specific entries should refer to particular enzymes involved in synthesis (e.g., ALOX15) or specific GPCR targets if known. “Resolvins are produced from DHA...and EPA...marine oils that enter humans via nutrition...The term ‘resolvin’ refers to unique structures...and potent pico-nanogram ability to counterregulate proinflammatories…” “Specialized pro-resolving mediators ...are formed ...by metabolism of polyunsaturated fatty acids ...by one or combination of lipoxygenase/cyclooxygenase/cytochrome P450 monooxygenase enzymes.” “Resolution of acute inflammation was introduced as passive ...but Dr Serhan’s group uncovered endogenous lipid mediators ...resolvins...pro-resolving lipid mediators stimulate efferocytosis..., recruit macrophages..., attenuate activated neutrophil through NF-kB inhibition…”

Other names

Lipid mediators and resolvins pathwaySpecialized pro-resolving mediators (SPM) pathwayPro-resolving lipid mediator biosynthesisOmega-3 fatty acid-derived mediator pathways