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Pinocembrin, a major flavonoid in propolis, improves the biological functions of EPCs derived from rat bone marrow through the PI3K-eNOS-NO signaling pathway

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Abstract

The number and quality of endothelial progenitor cells (EPCs) are damaged to varying degrees in patients at risk for developing atherosclerosis. The improvement of the quantity and functions of EPCs can enhance repair of injured endothelial monolayer resulting in inhibiting atherosclerosis. The purpose of this study was to investigate the effect of pinocembrin (PIN), a major flavonoid in propolis on the differentiation and biological functions of EPCs and the potential mechanisms of these effects. Flow cytometry analysis revealed that PIN treatment increased the number of CD34+, CD133+, FLK-1+, CD133+/FLK-1+ and CD34+/FLK-1+ mononuclear cells (MNCs) in the peripheral blood of apoE−/− mice compared to untreated control mice. In vitro PIN treatment significantly increased the number of CD34+, CD133+, FLK-1+ and CD133+/FLK-1+ MNCs derived from SD bone marrow compared to untreated controls by 42.1, 84.6, 165.9 and 23.1 %, respectively. Additionally, PIN can improve biological functions of EPCs, such as proliferation, migration, adhesion, and in vitro tube formation and NO release. All of these improvements were inhibited by LY294002, while L-NAME only inhibited the PIN-induced increase in EPC proliferation and adhesion. We conclude that PIN can both promote the differentiation of EPCs in vitro and ex vivo and improve the biological functions of EPCs. The PI3K-eNOS-NO signaling pathway may be involved in the PIN-induced increase in the proliferation and adhesion of EPCs.

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Abbreviations

MNCs:

Mononuclear cells

EPCs:

Endothelial progenitor cells

eNOS:

Endothelial nitric oxide synthase

FCM:

Flow cytometry

ac-LDL:

Acetylation-low-density lipoprotein

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (No. 30971098), the Province Natural Science Foundation of Shandong (No. Z2008C03), the Province Natural Science Foundation of Shandong (No. ZR2012HL18), Taishan Scholars Project Funding from Shandong Province and Natural Science Foundation of Taishan Medical University (2011ZR004). Science and technology plan projects of education department of Shandong (No. J07YD03).

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Correspondence to Shucun Qin.

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Yang, N., Qin, S., Wang, M. et al. Pinocembrin, a major flavonoid in propolis, improves the biological functions of EPCs derived from rat bone marrow through the PI3K-eNOS-NO signaling pathway. Cytotechnology 65, 541–551 (2013). https://doi.org/10.1007/s10616-012-9502-x

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