Icariin Attenuates Atherosclerosis via TNF/AKT/IL-6 Signaling Axis: Insights from Network Pharmacology and Experimental Validation in RAW264.7 Macrophages and ApoE −/− Mice

Atherosclerosis (AS) is a chronic vascular disease. Existing lipid-lowering therapies have limitations, so finding safer and more effective treatments is crucial. This study used network pharmacology, molecular docking, RAW264.7 macrophage in vitro and ApoE-deficient (ApoE ^−/− ) mouse in vivo experiments. It found 23 Epimedium bioactive components, with icariin being prominent. Key targets such as AKT1, TNF, and IL6 were identified, to which icariin exhibited strong binding affinity. In vivo, icariin reduced aortic arch thickness and plaque area, while improving dyslipidemia. In vitro, it inhibited macrophage foaming. These findings suggest that icariin combats AS by regulating the TNF/AKT/IL-6 axis, showcasing its multi-target therapeutic potential for AS treatment.