Silibinin augments the effect of clopidogrel on atherosclerosis in diabetic ApoE deficiency mice

Author:

Zhang Jianbo1,Shi Qiyu2,Hu Yamin1,Li Xiaohong3

Affiliation:

1. Department Cardiology 6, Cangzhou Central Hospital, Cangzhou, Hebei, China

2. Gastroenterology Department, Cangzhou People’s Hospital, Cangzhou, Hebei, China

3. Department Cardiology 3, Cangzhou Central Hospital, Cangzhou, Hebei, China

Abstract

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: In atherosclerotic mouse model, Silibinin significantly improves the effect of Clopidogrel on atherosclerosis.

Publisher

IOS Press

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Hematology,Physiology

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