Natural products targeting ferroptosis in depression: Research progress and therapeutic prospects

Depression is recognized as a chronic mental illness, also influenced by neurotransmitter homeostasis, with its incidence increasing annually worldwide. This condition inflicts significant physical and psychological harm, severely compromising human health. It exhibits a broad morbidity spectrum, and some current treatments and medications are hindered by short-term efficacy, strong side effects, and other limitations.

Due to the limitations, it is imperative to explore new treatment approaches and develop targeted drugs. Ferroptosis, a cell death mode dependent on iron, is believed to be intricately linked to the onset of depression. Thus, modulating cellular ferroptosis presents a promising avenue for the targeted therapy of depression.

We conducted a comprehensive search of databases such as PubMed, Elsevier ScienceDirect, Google Scholar, and CNKI, using keywords such as "ferroptosis", "depression", "iron death", "safety", "efficacy", and "effectiveness". Our review included original scientific articles, clinical trials, meta-analyses, and review papers published up to February 2025, focusing on studies excluding non-natural products.

Several natural products derived from plant, animal, or microbial sources effectively target ferroptosis, alleviating depressive symptoms and demonstrating unique and favorable outcomes. This review provides an exhaustive overview of the sources, pharmacological actions, mechanisms, efficacy, and safety of these natural products, highlighting their potential clinical benefits and offering a comprehensive perspective on their properties.

This study offers concrete ideas and valuable insights for the development and application of these natural products in the targeted treatment of depression.