Berberine-induced decline in circulating CD31+/CD42- microparticles is associated with improvement of endothelial...

Elevated circulating endothelial microparticles (EMPs) are associated with endothelial dysfunction. This study is to investigate whether berberine-induced fall in circulating EMPs facilitates improvement of endothelial function in healthy subjects. Fourteen healthy subjects received 1-month berberine therapy (1.2 g/d) and 11 healthy subjects served as control. Circulating EMPs were measured by flow cytometric analysis before and after therapy. Brachial artery endothelium-dependent and -independent function was assessed by flow-mediated vasodilation (FMD) and sublinqual nitroglyceride-mediated vasodilation (NMD). In vitro, human umbilical vein endothelial cells (HUVECs) were stimulated by EMPs (10(6)/ml) with or without the presence of berberine (10 microM). Intracellular endothelial nitric oxide synthase (eNOS) protein expression was detected by flow cytometry. After berberine therapy, circulating CD31(+)/CD42(-) microparticles were reduced, which was in parallel with the improvement of flow-mediated vasodilation while nitroglyceride-mediated vasodilation kept unchanged. A robust relationship was found between drop of circulating CD31(+)/CD42(-) microparticles and increased flow-mediated vasodilation. The EMPs in vitro led to diminished eNOS protein expression in HUVECs and this EMP-mediated detrimental effect was markedly inhibited by berberine. Berberine-induced decline in circulating CD31(+)/CD42(-) microparticles contributes to upregulation of endothelial function in healthy subjects. Deceasing EMPs may be a novel therapeutic target for the improvement of endothelial dysfunction in humans.