Protective effects of icariin in atherosclerotic cardiovascular disease: mechanistic basis, post-ischemic protection and translational limitations.

Abstract

Context: Icariin (ICA), a prenylated flavonol glycoside from Epimedii Folium, has been investigated in experimental models relevant to atherosclerosis, myocardial infarction, and ischemic tissue injury.

Objectives: This review evaluates experimental evidence on ICA in atherosclerotic plaque biology, post-myocardial infarction remodeling, myocardial ischemia-reperfusion injury, and cerebral ischemic injury.

Methods: PubMed and the Web of Science Core Collection were searched from database inception to 19 August 2026, and studies were selected using predefined eligibility criteria. Targeted searches also covered pharmacokinetics, metabolism, toxicology, botanical source, quality control, formulation, and delivery.

Results: In atherosclerosis models, ICA reduced endothelial inflammatory activation, macrophage lipid uptake, vascular smooth muscle cell (VSMC) proliferation and migration, and lesion burden. Several mechanistic links were tested using pharmacological or genetic perturbation. In vivo studies primarily characterized lesion burden and circulating lipids, with less direct assessment of plaque composition and stability. Post-myocardial infarction and ischemic injury studies reported reductions in fibrosis and ischemic tissue injury, together with reduced mitochondrial injury and changes in inflammatory signaling, apoptosis, and ferroptosis-related processes. Functional improvement was also reported in several models. Few studies measured parent ICA or metabolite concentrations in plaque, myocardium, or brain in the same experiments in which pathological outcomes were assessed.

Conclusions: Future studies should quantify parent ICA and active metabolites in diseased tissues while assessing plaque composition and stability in the same experiments, so that vascular effects can be related to measured in vivo exposure.