Ferroptosis and the Application of Traditional Chinese Medicine in Managing Type 2 Diabetes Mellitus

Abstract

The research field of ferroptosis has been enjoying exponential growth over the past few years, since the term was coined in 2012. This unique modality of cell death, driven by iron-dependent phospholipid peroxidation, is regulated by multiple cellular metabolic events, including redox homeostasis, iron handling, mitochondrial activity, and metabolism of amino acids, lipids and sugars, in addition to numerous signaling pathways relevant to disease. Intriguingly, therapy-resistant cancer cells, particularly those of the mesenchymal state and prone to metastasis, are exquisitely vulnerable to ferroptosis. Ferroptosis, an emerging form of regulated programmed cell death, has garnered significant attention in the past decade. It is characterized by the accumulation of lipid peroxides and subsequent damage to cellular membranes, which is dependent on iron. Under iron-rich and ROS conditions, phospholipids containing polyunsaturated fatty acids in the cell membranes are prone to peroxidation, resulting in the continuous accumulation of lipid peroxidation products. These products eventually disrupt cell membrane integrity and induce cell death. Ferroptosis has been implicated in the pathogenesis of various diseases, including tumors and diabetes mellitus. Traditional Chinese medicine (TCM) has unique advantages in preventing and treating type 2 diabetes mellitus (T2DM) due to its anti-inflammatory, antioxidant, immunomodulatory, and intestinal flora-regulating functions. Recent studies have determined that TCM may exert therapeutic effects on T2DM and its complications by modulating the ferroptosis-related pathways. Therefore, a comprehensive and systematic understanding of the role of ferroptosis in the pathogenesis and TCM treatment of T2DM is of great significance for developing therapeutic drugs for T2DM and enriching the spectrum of effective T2DM treatment with TCM. In this review, we review the concept, mechanism, and regulatory pathways of ferroptosis and the ferroptosis mechanism of action involved in the development of T2DM. Also, we develop a search strategy, establish strict inclusion and exclusion criteria, and summarize and analyze the application of the ferroptosis mechanism in TCM studies related to T2DM and its complications. Finally, we discuss the shortcomings of current studies and propose a future research focus.