Nrf2-mediated ferroptosis inhibition: a novel approach for managing inflammatory diseases

Inflammatory diseases, including psoriasis, atherosclerosis, rheumatoid arthritis, and ulcerative colitis, are characterized by persistent inflammation. Moreover, the existing treatments for inflammatory diseases only provide temporary relief by controlling symptoms, and treatments of unstable and expensive. Therefore, new therapeutic solutions are urgently needed to address the underlying causes or symptoms of inflammatory diseases. Inflammation frequently coincides with a high level of (reactive oxygen species) ROS activation, serving as a fundamental element in numerous physiological and pathological phenotypes that can result in serious harm to the organism. Given its pivotal role in inflammation, oxidative stress, and ferroptosis, ROS represents a focal node for investigating the (nuclear factor E2-related factor 2) Nrf2 pathway and ferroptosis, both of which are intricately linked to ROS. Ferroptosis is mainly triggered by oxidative stress and involves iron-dependent lipid peroxidation. The transcription factor Nrf2 targets several genes within the ferroptosis pathway. Recent studies have shown that Nrf2 plays a significant role in three key ferroptosis-related routes, including the synthesis and metabolism of glutathione/glutathione peroxidase 4, iron metabolism, and lipid processes. As a result, ferroptosis-related treatments for inflammatory diseases have attracted much attention. Moreover, drugs targeting Nrf2 can be used to manage inflammatory conditions. This review aimed to assess ferroptosis regulation mechanism and the role of Nrf2 in ferroptosis inhibition. Therefore, this review article may provide the basis for more research regarding the treatment of inflammatory diseases through Nrf2-inhibited ferroptosis.