Marine-Derived Natural Compounds in Respiratory Diseases: A Systematic Review of Preclinical Mechanisms, Clinical Evidence, and Translational Gaps

Marine-derived natural compounds have been investigated across respiratory diseases, but evidence remains fragmented across heterogeneous interventions, models, and outcomes. We mapped the evidence, examined biological convergence, and quantitatively synthesized comparable preclinical data. PubMed/MEDLINE, Scopus, and Web of Science were searched for studies published from 2000 to 2025; random-effects meta-analyses (Hedges’ g) were conducted for model–outcome combinations reported by at least three independent studies, with risk of bias and certainty assessed using design-specific tools and an adapted GRADE approach. Sixty-five studies were included (44 in vivo, 15 in vitro, 5 randomized trials, 1 non-randomized clinical study), with recurrent effects on inflammatory signalling, oxidative stress, immune regulation, tissue injury, and remodelling. Meta-analysis of 17 preclinical studies (60 comparisons, 11 outcomes) favoured marine-derived interventions for eosinophils, IgE-related outcomes, and type 2 cytokines in allergic airway models and for inflammatory/lung-injury markers in acute lung injury models, although heterogeneity was frequent and certainty was very low for all outcomes; clinical evidence was limited and heterogeneous. Marine-derived natural compounds show recurrent biological and directional convergence in selected preclinical respiratory models, but the evidence does not establish a therapeutic class effect or support direct clinical inference; translation requires standardized compound characterization, independent replication, and rigorous candidate prioritization.