Abstract
Diabetes mellitus (DM) abolishes the antithrombotic effect of Clopidogrel. Here, we investigated the synergistic effect of Silibinin on Clopidogrel-mediated atherosclerosis treatment in diabetic mice. ApoE-/- mice were fed with high-fat diet (HFD) to establish the atherosclerotic model with diabetes. Animals were treated with Clopidogrel, Silibinin, or the combined to evaluate the protective effects on atherosclerosis and diabetes through Oil-red-O staining, qRT-PCR, Western blot, and metabolic measurements. Platelet activation and aggregation ex vivo assays were performed to detect the anti-thrombotic effect of different administrations. Silibinin significantly enhanced the inhibitory effect of Clopidogrel on atherosclerosis in DM mice. Co-administration of Silibinin with Clopidogrel remarkedly reduced the aortic lesion, inflammation, and endothelial dysfunction in aorta roots, and diabetic symptoms were significantly improved by the Silibinin-Clopidogrel treatment in HFD-fed ApoE-/- mice. Interestingly, the anti-thrombotic effect of Clopidogrel was further augmented by the Silibinin treatment in atherosclerotic mice. In atherosclerotic mouse model, Silibinin significantly improves the effect of Clopidogrel on atherosclerosis.
Published Version
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