Polyunsaturated fatty acids (PUFAs), particularly omega-3 derivatives such as docosahexaenoic acid (DHA), are precursors of specialized pro-resolving mediators (SPMs) that actively orchestrate the resolution of inflammation. Among these, maresins (MaRs) have gathered increasing attention due to their potent immunomodulatory and tissue-regenerative properties. This review provides a comprehensive synthesis of the current knowledge on the biosynthesis, structural diversity, and biological functions of MaRs, with a focus on MaR1. We discuss the enzymatic pathways involved in the generation of MaR1, MaR2, MaRs conjugates in tissue regeneration (MCTRs), and maresin-like lipid mediators (MaR-Ls), highlighting their roles in modulating inflammatory responses, promoting phagocytosis, and restoring tissue homeostasis. Preclinical evidence from in vitro and in vivo models demonstrates that MaRs exert protective effects in a wide range of pathological contexts, including neuroinflammation, liver injury, cardiovascular dysfunction, pulmonary diseases, and metabolic disorders. Although their therapeutic promise is well-supported, key gaps remain in the understanding of MaRs biosynthesis, receptor specificity, and translational applicability. This review emphasizes the importance of advancing mechanistic and clinical research to fully harness MaRs as part of next-generation therapeutics in inflammation-driven diseases.

Diabetic cardiomyopathy (DCM) is a major cause of heart failure in patients with diabetes and arises from chronic metabolic stress, oxidative injury, infla

Background/Objectives: Maresin 1 (MaR1), a pro-resolving mediator derived from docosahexaenoic acid (DHA), differs from DHA in its C7/C14 hydroxylation pattern and double-bond arrangement. We compared their recognition by peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ (PPARγ), and retinoic acid receptor-related orphan receptor α (RORα) in the context of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: We validated Glide docking by redocking reference ligands and performed four independent 250 ns molecular dynamics simulations per complex (24 trajectories; 6.0 μs). We evaluated structural stability, replica-resolved contacts, oxygen distance profiles, and conformational sampling; relative energetic estimates were obtained using molecular mechanics/generalized Born surface area (MM-GBSA) calculations. Results: Redocking RMSDs were ≤1.5 Å, and the replicated trajectories showed no ligand dissociation. In PPARα, MaR1 showed recurrent C7-OH–Lys358 proximity and reproducible carboxylate-associated contacts with Tyr314 and Ser280. In PPARγ, the MaR1 carboxylate sampled Tyr473 in helix 12 and HIE323 with replica-dependent geometry, whereas DHA retained an Arg288-centered anchor. In RORα, MaR1 preferentially sampled an Arg370-centered arrangement, whereas DHA predominantly engaged Arg367; both ligands displayed replica-dependent alternative polar contacts. MaR1 showed more negative hydrogen-bonding, lipophilic, and van der Waals contributions and lower numerical total MM-GBSA scores than DHA across all three receptor pairs. Conclusions: MaR1 showed receptor-specific redistribution of polar contacts associated with alternative carboxylate positioning. Although the calculations do not establish binding affinity or receptor activation, these patterns, rather than a conserved direct C7-OH/C14-OH recognition motif, define testable interaction sites for matched-analog studies and functional assays.