Mechanistic Study of Erchen Decoction Combined with Taohong Siwu Decoction in Ameliorating Atherosclerosis in ApoE⁻/⁻ Mice by Inhibiting Ferroptosis via the p53/SLC7A11 Pathway

Abstract

Objective： This study aimed to evaluate whether Erchen Decoction combined with Taohong Siwu Decoction exerts anti-atherosclerotic effects by modulating the p53/SLC7A11 pathway and ferroptosis. Methods： An atherosclerosis model was established by feeding ApoE⁻/⁻ mice a high-fat diet. The mice were randomly divided into five groups: model group, low-, medium-, and high-dose TCM groups, and a simvastatin group, with a normal-diet group serving as control. Following 4 weeks of treatment, aortic plaque formation was examined, serum levels of SOD, MDA, and GSH were assessed, and protein and mRNA expression in aortic tissues were detected via immunohistochemistry and RT-PCR. Results： Compared with the model group, the combined administration of Erchen Decoction and Taohong Siwu Decoction markedly reduced aortic plaque area, elevated serum SOD and GSH activities, and lowered MDA levels (P < 0.05 or P < 0.01). Additionally, it downregulated mRNA expression of p53, PTGS2, and NOX1 and COX2 protein expression in aortic tissue, while upregulating mRNA expression of SLC7A11, GPX4, and FTH1, as well as FTH1 protein expression. Conclusion: Erchen Decoction combined with Taohong Siwu Decoction may exert anti-atherosclerotic effects by inhibiting p53 expression and activating the SLC7A11/GPX4 axis, thereby alleviating oxidative damage and suppressing ferroptosis.