Berberine Decreases Thrombosis Potential Induced by a High-choline Diet by Inhibiting CutC Enzyme

Abstract

Introduction: Gut microbes influence thrombosis potential by generating trimethylamine N-oxide (TMAO). However, whether the antithrombotic effect of berberine is associated with TMAO generation remains unclear.

Objective: The present study was designed to explore whether berberine decreases the TMAO-induced thrombosis potential and the possible mechanism underneath it.

Methods: C57BL/6J female mice under a high-choline diet or standard diet were treated with/without berberine for 6 weeks. The TMAO level, carotid artery occlusion time following FeCl₃ injury and platelet responsiveness were measured. The binding of berberine to the CutC enzyme was analysed with molecular docking, and molecular dynamics simulations were verified with enzyme activity assays.

Results: The results showed that berberine increased the carotid artery occlusion time following FeCl₃ injury and decreased the platelet hyperresponsiveness induced by a high-- choline diet, both offset by intraperitoneal injection of TMAO. The effect of berberine on thrombosis potential was associated with decreasing the generation of TMAO by inhibiting the CutC enzyme.

Conclusion: Targeting TMAO generation with berberine might be a promising therapy for ischaemic cardiac-cerebral vascular diseases.

Keywords: Berberine; enzyme.; microbiota; platelet; thrombosis potential gut; trimethylamine N-oxide.