The role of tetramethylpyrazine and paeoniflorin in modulating iron metabolism and ferroptosis: innovative strategies for atherosclerosis treatment

Introduction: Atherosclerosis (AS) is driven by lipid accumulation, inflammation, and oxidative stress, leading to endothelial dysfunction and plaque formation. Emerging evidence indicates that iron overload and ferroptosis exacerbate these processes via enhanced lipid peroxidation and vascular injury. However, current Western medical strategies predominantly target lipid-lowering and inflammation, often overlooking iron dysregulation and ferroptotic pathways. Methods: mice as an AS model and administered Tetramethylpyrazine (TMP), Paeoniflorin (PF), or their combination (TMP+PF). Serum lipids, oxidative stress biomarkers, iron metabolism indices, and ferroptosis-related markers were measured. Results: Both TMP and PF significantly reduced serum lipid levels and oxidative stress, normalized iron metabolism parameters, and suppressed ferroptosis-associated markers, indicating a protective effect against ferroptotic damage. Discussion: These findings suggest that TMP and PF mitigate AS by coordinately regulating oxidative stress, iron homeostasis, and ferroptosis. Their multi-targeted action may offer a complementary approach to conventional therapies, addressing the previously neglected mechanisms of iron-driven vascular pathology.