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【转载】Pro-angiogenic activity of notoginsenoside R1......(三七皂苷R1体外对人体脐静脉内皮细胞和体内对斑马鱼化学诱导所致血管损失模型的促血管生成活性研究)  

2016-12-16 18:02:47|  分类: 默认分类 |  标签: |举报 |字号 订阅

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Pro-angiogenic activity of notoginsenoside R1 in human umbilical vein endothelial cells in vitro and in a chemical-induced blood vessel loss model of zebrafish in vivo

(三七皂苷R1体外对人体脐静脉内皮细胞和体内对斑马鱼化学诱导所致血管损失模型的促血管生成活性研究)

B YangS HongSM LeeW CongJ Wan..

Chinese Journal of Integrative Medicine

June 2016, Volume 22, Issue 6, pp 420–429

 2016年12月13日 - 草木山川 - 药学文献与研究

 

    Abstract

Objective

This study aimed at investigating whether notoginsenoside R1 (R1), a unique saponin found in Panax notoginseng could promote angiogenic activity on human umbilical vein endothelial cells (HUVECs) and elucidate their potential molecular mechanisms. In addition, vascular restorative activities of R1 was assessed in a chemically-induced blood vessel loss model in zebrafish.

2016年12月13日 - 草木山川 - 药学文献与研究

 

Methods

The in vitro angiogenic effect of R1 was compared with other previously reported angiogenic saponins Rg1 and Re. The HUVECs proliferation in the presence of R1 was determined by cell proliferation kit II (XTT) assay. R1, Rg1 and Re-induced HUVECs invasion across polycarbonate membrane was stained with Hoechst-33342 and quantified microscopically. Tube formation assay using matrigelcoated wells was performed to evaluate the pro-angiogenic actions of R1. In order to understand the mechanism underlying the pro-angiogenic effect, various pathway inhibitors such as SU5416, wortmannin (wort) or L-Nω-nitro- L-arginine methyl ester hydrochloride (L-NAME), SH-6 were used to probe the possible involvement of signaling pathway in the R1 mediated HUVECs proliferation. In in vivo assays, zebrafish embryos at 21 hpf were pre-treated with vascular endothelial growth factor (VEGF) receptor kinase inhibitor II (VRI) for 3 h only and subsequently post-treated with R1 for 48 h, respectively. The intersegmental vessels (ISVs) in zebrafish were assessed for the restorative effect of R1 on defective blood vessels.

 2016年12月13日 - 草木山川 - 药学文献与研究

 Results

R1 could stimulate the proliferation of HUVECs. In the chemoinvasion assay, R1 significantly increased the number of cross-membrane HUVECs. In addition, R1 markedly enhanced the tube formation ability of HUVECs. The proliferative effects of these saponins on HUVECs were effectively blocked by the addition of SU5416 (a VEGF-KDR/Flk-1 inhibitor). Similarly, pre-treatment with wort [a phosphatidylinositol 3-kinase (PI3K)-kinase inhibitor], L-NAME [an endothelial nitric oxide synthase (eNOS) inhibitor] or SH-6 (an Akt pathway inhibitor) significantly abrogated the R1 induced proliferation of HUVECs. In chemicallyinduced blood vessel loss model in zebrafish, R1 significantly rescue the damaged ISVs.

 2016年12月13日 - 草木山川 - 药学文献与研究

Conclusion

R1, similar to Rg1 and Re, had been showed pro-angiogenic action, possibly via the activation of the VEGF-KDR/Flk-1 and PI3K-Akt-eNOS signaling pathways. Our findings also shed light on intriguing pro-angiogenic effect of R1 under deficient angiogenesis condition in a pharmacologic-induced blood vessels loss model in zebrafish. The present study in vivo and in vitro provided scientific evidence to explain the ethnomedical use of Panax notoginseng in the treatment of cardiovascular diseases, traumatic injuries and wound healing.

2016年12月13日 - 草木山川 - 药学文献与研究

Keywords

notoginsenoside R1  ginsenoside Rg1  ginsenoside Re   human umbilical vein   endothelial cell  zebrafish  angiogenesis

Supported by grants from the Overseas and Hong Kong, Macau Young Scholars Collaborative Research Fund by the National Natural Science Foundation of China (No. 81328025) and the Science and Technology Development Fund of Macau SAR (Ref. No. 014/2011/A1), Research Committee, University of Macau

These authors contributed equally to this work

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