Resveratrol in depression: mechanistic networks, preclinical evidence and translational perspectives

Abstract

Abstract Objectives Depression involves interacting immune, oxidative, metabolic, neuroendocrine and neuroplasticity networks. This review evaluates mechanistic, preclinical, human and translational evidence for resveratrol in depression. Methods We conducted a structured narrative review of English-language literature to 30 June 2026 using PubMed, Web of Science Core Collection, Scopus and ScienceDirect, supplemented by Google Scholar and citation searching. After duplicate removal, 4,461 records were screened, 142 full texts assessed and 71 publications included. Results Antidepressant-like effects were reported across stress, endocrine, developmental, post-stroke, metabolic and gut-inflammatory models, involving SIRT1/AMPK, NF-κB/ NLRP3, Nrf2/HO-1, mitochondrial and ferroptosis pathways,monoaminergic and cAMP/PKA/CREB/BDNF signalling, and gut brain communication. However, many studies used preventive or concurrent dosing, male animals, high doses or non-oral routes. Human studies were few, heterogeneous and mainly non psychiatric, and do not establish efficacy for major depressive disorder. Nanoformulations may improve exposure, but depression specific clinical validation is lacking. Conclusions Current evidence does not support resveratrol as monotherapy or an established depression treatment. It is better positioned as a mechanistic probe and hypothesis-generating adjunctive candidate. Future studies should prioritise therapeutic designs, pharmacokinetic monitoring, standardised outcomes and adequately powered adjunctive trials.