Pro-resolving lipid mediators in diseases: exploring the molecular basis and clinical implication.

Inflammation resolution is now understood as an active and highly coordinated biological process rather than a passive decline in inflammatory signals. When this program fails, inflammation may become persistent and gradually shift to a chronic pathological state. Such unresolved inflammation is increasingly recognized as a core driver of cardiovascular disease, metabolic disorders, autoimmune pathologies, neurodegeneration, and tumor progression. Although conventional anti-inflammatory drugs can suppress inflammatory mediators, they do not restore immune balance or actively promote resolution, and long-term administration may disrupt host defense and tissue-repair processes. Pro-resolving lipid mediators (PRLMs), including resolvins, maresins, protectins, and lipoxins, represent a distinct class of bioactive metabolites derived from polyunsaturated fatty acids. Recent studies have demonstrated that PRLMs regulate inflammation through specialized pro-resolving programs, such as enhancing efferocytosis, modulating cytokine networks, guiding leukocyte trafficking, and promoting tissue regeneration via receptor-dependent signaling pathways. These findings highlight a conceptual shift in inflammation management from broadly inhibiting inflammation to restoring immune homeostasis. Despite encouraging progress, several challenges hinder clinical translation, including rapid metabolic inactivation, limited delivery strategies, and unresolved pharmacological parameters. In this review, we summarize the current advances in PRLM biosynthesis, signaling pathways, and biological functions across multiple disease contexts. We also discuss emerging therapeutic strategies, biomarker development, and knowledge gaps that require further investigation. PRLM research offers a promising framework for next-generation resolution-based therapeutic interventions.