Matrine as a multi-disease regulator of ferroptosis: mechanisms, therapeutic applications, and toxicity management.
Matrine is the main active metabolite of Sophora flavescens Ait. Matrine is a traditional medicine with a long history of medicinal use. Modern pharmacological research confirms that matrine possesses a variety of pharmacological effects, including anti-inflammatory, immunomodulatory, and anti-parasitic activities. Ferroptosis is a form of programmed cell death characterized by iron accumulation and lipid peroxidation. Recent studies show that matrine achieves organ protection or therapeutic effects in various diseases by regulating the shared pathway of ferroptosis. This review explores the multi-target intervention role of matrine in cardiovascular diseases, central nervous system diseases, acute lung injury induced by severe acute pancreatitis, and cervical cancer through the mechanism of ferroptosis. By comparing and deeply analyzing different research findings, the review provides a theoretical basis for future research and potential drug development. It also integrates existing preclinical evidence and emphasizes the need for rigorous, multi-center, and large-scale clinical studies to accelerate the translation of matrine from the laboratory to clinical practice. The cross-disease therapeutic potential of matrine via ferroptosis regulation positions it as a candidate molecule linking the multi-target advantages of natural metabolites with modern precision medicine. However, its dose-dependent tissue toxicity necessitates that future research integrate derivative optimization, targeted delivery systems, and biomarker-based individualized dosing strategies to achieve a safe transition from laboratory to clinical practice.