Natural medicine-empowered treatment of depression via restoring neurogenesis (Review)

Abstract

Major depressive disorder (MDD) remains a leading cause of disability, with a substantial proportion of patients failing to achieve adequate remission following conventional monoaminergic antidepressant treatment. The present narrative review examines evidence primarily published between 2015 and 2025 concerning natural medicines, including phytochemicals, traditional formulations, marine-derived products and dietary polyphenols, that may modulate neurogenesis relevant to depression. Adult hippocampal neurogenesis is regarded as one mechanistic framework rather than the sole explanation for depressive pathology. Priority was given to clinical and human-derived evidence, while preclinical studies are employed to elucidate underlying mechanisms. Natural products appear to converge on pathways involving brain-derived neurotrophic factor/tropomyosin receptor kinase B, Wnt/β-catenin, NF-κB/NLR family pyrin domain containing 3-mediated immune regulation, autophagy, mitochondrial bioenergetics and the gut microbiota. Nevertheless, current clinical evidence remains insufficient to support the use of natural medicines as substitutes for established antidepressant therapies. Their most plausible near-term application lies in standardized adjunctive or investigational interventions, pending larger biomarker-stratified trials, rigorous safety assessment and optimized formulation strategies.