# Ferroptosis as a therapeutic nexus: traditional Chinese medicine interventions in rheumatoid arthritis

## TL;DR

This review explores how traditional Chinese medicine can treat rheumatoid arthritis by targeting ferroptosis, a type of cell death linked to iron metabolism and immune regulation.

## Contribution

The paper systematically reviews how TCM modulates ferroptosis pathways to treat rheumatoid arthritis, offering new therapeutic insights.

## Key findings

- TCM regulates iron metabolism and activates antioxidant pathways to alleviate RA symptoms.
- Ferroptosis pathways, including NCOA4-mediated ferritin autophagy, are dysregulated in RA.
- Modulating ferroptosis provides a novel therapeutic strategy for RA treatment.

## Abstract

Ferroptosis is an iron-dependent, lipid peroxidation-driven form of programmed cell death that plays an important role in neurodegenerative, neoplastic, and autoimmune diseases. Recent studies in Rheumatoid arthritis (RA) have shown that iron metabolism disorders caused by iron overload and impaired transferrin function lead to the production of reactive oxygen species; ferroptosis-associated pathways, such as dysregulation of the System Xc-/GPX4 axis dysregulation, NCOA4-mediated ferritin autophagy, endoplasmic reticulum stress and ferroptosis pathway crosstalk; as well as ferroptosis plays a regulatory role in a variety of immune cells, such as T-cells, B-cells, macrophages, etc., which collectively constitute a complex disease regulatory network in RA. Studies have shown that traditional Chinese medicine (TCM) and TCM therapeutics can alleviate RA-related symptoms and improve the disease progression and prognosis of RA by regulating iron metabolism, activating the Nrf2/HO-1 antioxidant pathway, and removing abnormally proliferating synovial fibroblasts (FLS cells). The aim of this review is to comprehensively summarize the therapeutic potential of TCM for RA using ferroptosis as a therapeutic pathway. The aim is to provide a scientific basis for the clinical application of TCM in RA. In major scientific databases (including PubMed, Web of Science, ScienceDirect, and CNKI, covering literature published up to June 2025). The search strategy combines “Chinese medicine”, “TCM”, “ferroptosis”, and “rheumatoid arthritis”, using Boolean operators (AND, OR). This review systematically elucidates the mechanistic underpinnings through which TCM mitigates RA by modulating ferroptosis pathways. This review highlights the potential that Chinese medicine holds in the treatment of RA. The use of ferroptosis as a therapeutic pivot provides new ideas for the treatment of RA and promotes the integration of Western and Chinese medicine.