{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T16:19:44Z","timestamp":1783959584525,"version":"3.55.0"},"reference-count":37,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T00:00:00Z","timestamp":1419206400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Chin. J. Integr. Med."],"published-print":{"date-parts":[[2016,6]]},"DOI":"10.1007\/s11655-014-1954-8","type":"journal-article","created":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T19:09:18Z","timestamp":1419275358000},"page":"420-429","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["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"],"prefix":"10.1007","volume":"22","author":[{"given":"Bin-rui","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-jia","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon Ming-Yuen","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-hong","family":"Cong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-bo","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe-rui","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing-wen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-tao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-xiu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2014,12,22]]},"reference":[{"key":"1954_CR1","doi-asserted-by":"crossref","first-page":"4763","DOI":"10.1242\/dev.068023","volume":"138","author":"S Arima","year":"2011","unstructured":"Arima S, Nishiyama K, Ko T, Arima Y, Hakozaki Y, Sugihara K, et al. Angiogenic morphogenesis driven by dynamic and heterogeneous collective endothelial cell movement. Development 2011;138:4763\u20134776.","journal-title":"Development"},{"key":"1954_CR2","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s12013-008-9030-7","volume":"52","author":"S Chatterjee","year":"2008","unstructured":"Chatterjee S, Chapman KE, Fisher AB. Lung ischemia: a model for endothelial mechanotransduction. Cell Biochem Biophys 2008;52:125\u2013138.","journal-title":"Cell Biochem Biophys"},{"key":"1954_CR3","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.bbrc.2009.11.045","volume":"391","author":"BH Chung","year":"2010","unstructured":"Chung BH, Lee JJ, Kim JD, Jeoung D, Lee H, Choe J, et al. Angiogenic activity of sesamin through the activation of multiple signal pathways. Biochem Biophys Res Commun 2010;391:254\u2013260.","journal-title":"Biochem Biophys Res Commun"},{"key":"1954_CR4","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1210\/er.2003-0027","volume":"25","author":"N Ferrara","year":"2004","unstructured":"Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004;25:581\u2013611.","journal-title":"Endocr Rev"},{"key":"1954_CR5","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/21224","volume":"399","author":"S Dimmeler","year":"1999","unstructured":"Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AM. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature 1999;399:601\u2013605.","journal-title":"Nature"},{"key":"1954_CR6","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1517\/13543784.2014.892582","volume":"23","author":"J Liu","year":"2014","unstructured":"Liu J, Wang Y, Qiu L, Yu Y, Wang C. Saponins of Panax notoginseng: chemistry, cellular targets and therapeutic opportunities in cardiovascular diseases. Expert Opin Investig Drugs 2014;23:523\u2013539.","journal-title":"Expert Opin Investig Drugs"},{"key":"1954_CR7","doi-asserted-by":"crossref","first-page":"6692","DOI":"10.1021\/jf900529w","volume":"57","author":"JB Wan","year":"2009","unstructured":"Wan JB, Lee SM, Wang JD, Wang N, He CW, Wang YT, et al. Panax notoginseng reduces atherosclerotic lesions in ApoE-deficient mice and inhibits TNF-alpha-induced endothelial adhesion molecule expression and monocyte adhesion. J Agric Food Chem 2009;57:6692\u20136697.","journal-title":"J Agric Food Chem"},{"key":"1954_CR8","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/1749-8546-6-37","volume":"6","author":"N Wang","year":"2011","unstructured":"Wang N, Wan JB, Chan SW, Deng YH, Yu N, Zhang QW, et al. Comparative study on saponin fractions from Panax notoginseng inhibiting inflammation-induced endothelial adhesion molecule expression and monocyte adhesion. Chin Med 2011;6:37.","journal-title":"Chin Med"},{"key":"1954_CR9","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/bph.12435","volume":"171","author":"B Gao","year":"2014","unstructured":"Gao B, Huang L, Liu H, Wu H, Zhang E, Yang L, et al. Platelet P2Y(1)(2) receptors are involved in the haemostatic effect of notoginsenoside Ft1, a saponin isolated from Panax notoginseng. Br J Pharmacol 2014;171:214\u2013223.","journal-title":"Br J Pharmacol"},{"key":"1954_CR10","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1002\/ptr.5026","volume":"28","author":"R Uzayisenga","year":"2014","unstructured":"Uzayisenga R, Ayeka PA, Wang Y. Anti-diabetic potential of Panax Notoginseng Saponins (PNS): a review. Phytother Res 2014;28:510\u2013516.","journal-title":"Phytother Res"},{"key":"1954_CR11","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.jep.2011.11.040","volume":"139","author":"N Ning","year":"2012","unstructured":"Ning N, Dang X, Bai C, Zhang C, Wang K. Panax notoginsenoside produces neuroprotective effects in rat model of acute spinal cord ischemia-reperfusion injury. J Ethnopharmacol 2012;139:504\u2013512.","journal-title":"J Ethnopharmacol"},{"key":"1954_CR12","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1021\/np070613q","volume":"71","author":"Y Usami","year":"2008","unstructured":"Usami Y, Liu YN, Lin AS, Shibano M, Akiyama T, Itokawa H, et al. Antitumor agents. 261. 20(S)-protopanaxadiol and 20(S)-protopanaxatriol as antiangiogenic agents and total assignment of H-1 NMR spectrao. J Natural Products 2008;71:478\u2013481.","journal-title":"J Natural Products"},{"key":"1954_CR13","doi-asserted-by":"crossref","first-page":"1596","DOI":"10.1016\/j.jpba.2006.01.058","volume":"41","author":"JB Wan","year":"2006","unstructured":"Wan JB, Yang FQ, Li SP, Wang YT, Cui XM. Chemical characteristics for different parts of Panax notoginseng using pressurized liquid extraction and HPLC-ELSD. J Pharm Biomed Anal 2006;41:1596\u20131601.","journal-title":"J Pharm Biomed Anal"},{"key":"1954_CR14","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.ijpharm.2006.08.009","volume":"328","author":"LC Yu","year":"2007","unstructured":"Yu LC, Chen SC, Chang WC, Huang YC, Lin KM, Lai PH, et al. Stability of angiogenic agents, ginsenoside Rg1 and Re, isolated from Panax ginseng: in vitro and in vivo studies. Int J Pharm 2007;328:168\u2013176.","journal-title":"Int J Pharm"},{"key":"1954_CR15","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S0303-7207(97)00160-3","volume":"133","author":"YJ Lee","year":"1997","unstructured":"Lee YJ, Chung E, Lee KY, Lee YH, Huh B, Lee SK. Ginsenoside-Rg1, one of the major active molecules from Panax ginseng, is a functional ligand of glucocorticoid receptor. Mol Cell Endocrinol 1997;133:135\u2013140.","journal-title":"Mol Cell Endocrinol"},{"key":"1954_CR16","doi-asserted-by":"crossref","first-page":"3211","DOI":"10.1016\/j.febslet.2006.04.080","volume":"580","author":"KW Leung","year":"2006","unstructured":"Leung KW, Cheng YK, Mak NK, Chan KK, Fan TP, Wong RN. Signaling pathway of ginsenoside-Rg1 leading to nitric oxide production in endothelial cells. FEBS Lett 2006;580:3211\u20133216.","journal-title":"FEBS Lett"},{"key":"1954_CR17","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.ygcen.2004.11.003","volume":"140","author":"CQ Ling","year":"2005","unstructured":"Ling CQ, Yong L, Zhu XY, Chen Z, Min L. Ginsenosides may reverse the dexamethasone-induced down-regulation of glucocorticold receptor. Gener Compar Endocrinol 2005;140:203\u2013209.","journal-title":"Gener Compar Endocrinol"},{"key":"1954_CR18","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1161\/01.CIR.0000140676.88412.CF","volume":"110","author":"S Sengupta","year":"2004","unstructured":"Sengupta S, Toh SA, Sellers LA, Skepper JN, Koolwijk P, Leung HW, et al. Modulating angiogenesis: the yin and the yang in ginseng. Circulation 2004;110:1219\u20131225.","journal-title":"Circulation"},{"key":"1954_CR19","doi-asserted-by":"crossref","first-page":"1916","DOI":"10.1124\/mol.106.028134","volume":"70","author":"T Furukawa","year":"2006","unstructured":"Furukawa T, Bai CX, Kaihara A, Ozaki E, Kawano T, Nakaya Y, et al. Ginsenoside Re, a main phytosterol of Panax ginseng, activates cardiac potassium channels via a nongenomic pathway of sex hormones. Mol Pharmacol 2006;70:1916\u20131924.","journal-title":"Mol Pharmacol"},{"key":"1954_CR20","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.vph.2005.12.002","volume":"44","author":"HS Zhang","year":"2006","unstructured":"Zhang HS, Wang SQ. Notoginsenoside R1 from Panax notoginseng inhibits TNF-alpha-induced PAI-1 production in human aortic smooth muscle cells. Vascul Pharmacol 2006;44:224\u2013230.","journal-title":"Vascul Pharmacol"},{"key":"1954_CR21","doi-asserted-by":"crossref","first-page":"1758","DOI":"10.1111\/bph.12063","volume":"168","author":"B Sun","year":"2013","unstructured":"Sun B, Xiao J, Sun XB, Wu Y. Notoginsenoside R1 attenuates cardiac dysfunction in endotoxemic mice: an insight into oestrogen receptor activation and PI3K\/Akt signalling. Br J Pharmacol 2013;168:1758\u20131770.","journal-title":"Br J Pharmacol"},{"key":"1954_CR22","doi-asserted-by":"crossref","first-page":"445","DOI":"10.3109\/10715762.2014.885117","volume":"48","author":"X Meng","year":"2014","unstructured":"Meng X, Sun G, Ye J, Xu H, Wang H, Sun X. Notoginsenoside R1-mediated neuroprotection involves estrogen receptor-dependent crosstalk between Akt and ERK1\/2 pathways: a novel mechanism of Nrf2\/ARE signaling activation. Free Radic Res 2014;48:445\u2013460.","journal-title":"Free Radic Res"},{"key":"1954_CR23","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1097\/SHK.0b013e3181ceede4","volume":"34","author":"WJ Liu","year":"2010","unstructured":"Liu WJ, Tang HT, Jia YT, Ma B, Fu JF, Wang Y, et al. Notoginsenoside R1 attenuates renal ischemia-reperfusion injury in rats. Shock 2010;34:314\u2013320.","journal-title":"Shock"},{"key":"1954_CR24","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1002\/jcb.21403","volume":"103","author":"HW Lam","year":"2008","unstructured":"Lam HW, Lin HC, Lao SC, Gao JL, Hong SJ, Leong CW, et al. The angiogenic effects of Angelica sinensis extract on HUVEC in vitro and zebrafish in vivo. J Cell Biochem 2008;103:195\u2013211.","journal-title":"J Cell Biochem"},{"key":"1954_CR25","doi-asserted-by":"crossref","first-page":"42997","DOI":"10.1074\/jbc.M204764200","volume":"277","author":"T Tanimoto","year":"2002","unstructured":"Tanimoto T, Jin ZG, Berk BC. Transactivation of vascular endothelial growth factor (VEGF) receptor Flk-1\/KDR is involved in sphingosine 1-phosphate-stimulated phosphorylation of Akt and endothelial nitric-oxide synthase (eNOS). J Biol Chem 2002;277:42997\u201343001.","journal-title":"J Biol Chem"},{"key":"1954_CR26","doi-asserted-by":"crossref","first-page":"5281","DOI":"10.1242\/dev.00733","volume":"130","author":"S Isogai","year":"2003","unstructured":"Isogai S, Lawson ND, Torrealday S, Horiguchi M, Weinstein BM. Angiogenic network formation in the developing vertebrate trunk. Development 2003;130:5281\u20135290.","journal-title":"Development"},{"key":"1954_CR27","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/cbdv.200690074","volume":"3","author":"HX Sun","year":"2006","unstructured":"Sun HX, Chen Y, Ye Y. Ginsenoside Re and notoginsenoside R1: immunologic adjuvants with low haemolytic effect. Chem Biodivers 2006;3:718\u2013726.","journal-title":"Chem Biodivers"},{"key":"1954_CR28","doi-asserted-by":"crossref","first-page":"H336","DOI":"10.1152\/ajpheart.01105.2004","volume":"289","author":"M Milkiewicz","year":"2005","unstructured":"Milkiewicz M, Hudlicka O, Brown MD, Silgram H. Nitric oxide, VEGF, and VEGFR-2: interactions in activity-induced angiogenesis in rat skeletal muscle. Am J Physiol Heart Circ Physiol 2005;289:H336\u2013H343.","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"1954_CR29","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ejphar.2004.07.062","volume":"498","author":"G Bocci","year":"2004","unstructured":"Bocci G, Danesi R, Marangoni G, Fioravanti A, Boggi U, Esposito I, et al. Antiangiogenic versus cytotoxic therapeutic approaches to human pancreas cancer: an experimental study with a vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor and gemcitabine. Eur J Pharmacol 2004;498:9\u201318.","journal-title":"Eur J Pharmacol"},{"key":"1954_CR30","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1517\/13543784.16.1.83","volume":"16","author":"A Kiselyov","year":"2007","unstructured":"Kiselyov A, Balakin KV, Tkachenko SE. VEGF\/VEGFR signalling as a target for inhibiting angiogenesis. Expert Opinion Investig Drugs 2007;16:83\u2013107.","journal-title":"Expert Opinion Investig Drugs"},{"key":"1954_CR31","doi-asserted-by":"crossref","first-page":"3222","DOI":"10.1074\/jbc.M002016200","volume":"276","author":"H Gille","year":"2001","unstructured":"Gille H, Kowalski J, Li B, LeCouter J, Moffat B, Zioncheck TF, et al. Analysis of biological effects and signaling properties of Flt-1 (VEGFR-1) and KDR (VEGFR-2). A reassessment using novel receptor-specific vascular endothelial growth factor mutants. J Biol Chem 2001;276:3222\u20133230.","journal-title":"J Biol Chem"},{"key":"1954_CR32","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1016\/S0002-9440(10)61775-0","volume":"159","author":"B Bussolati","year":"2001","unstructured":"Bussolati B, Dunk C, Grohman M, Kontos CD, Mason J, Ahmed A. Vascular endothelial growth factor receptor-1 modulates vascular endothelial growth factor-mediated angiogenesis via nitric oxide. Am J Pathol 2001;159:993\u20131008.","journal-title":"Am J Pathol"},{"key":"1954_CR33","doi-asserted-by":"crossref","first-page":"6616","DOI":"10.1158\/0008-5472.CAN-04-0401","volume":"64","author":"G Bocci","year":"2004","unstructured":"Bocci G, Man S, Green SK, Francia G, Ebos JML, du Manoir JM, et al. Increased plasma vascular endothelial growth factor (VEGF) as a surrogate marker for optimal therapeutic dosing of VEGF receptor-2 monoclonal antibodies. Cancer Res 2004;64:6616\u20136625.","journal-title":"Cancer Res"},{"key":"1954_CR34","doi-asserted-by":"crossref","first-page":"36280","DOI":"10.1074\/jbc.M606698200","volume":"281","author":"KW Leung","year":"2006","unstructured":"Leung KW, Pon YL, Wong RNS, Wong AST. Ginsenoside-Rg1 induces vascular endothelial growth factor expression through the glucocorticoid receptor-related phosphatidylinositol 3-kinase\/Akt and beta-catenin\/T-cell factor-dependent pathway in human endothelial cells. J Biol Chemi 2006;281:36280\u201336288.","journal-title":"J Biol Chemi"},{"key":"1954_CR35","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2174\/138620712801619140","volume":"15","author":"F Miscevic","year":"2012","unstructured":"Miscevic F, Rotstein O, Wen XY. Advances in zebrafish high content and high throughput technologies. Comb Chem High Throughput Screen 2012;15:515\u2013521.","journal-title":"Comb Chem High Throughput Screen"},{"key":"1954_CR36","first-page":"605303","volume":"2012","author":"MW Hung","year":"2012","unstructured":"Hung MW, Zhang ZJ, Li S, Lei B, Yuan S, Cui GZ, et al. From omics to drug metabolism and high content screen of natural product in zebrafish: a new model for discovery of neuroactive compound. Evid Based Complement Alternat Med 2012;2012:605303.","journal-title":"Evid Based Complement Alternat Med"},{"key":"1954_CR37","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1055\/s-0033-1360394","volume":"80","author":"S Limsuwanchote","year":"2014","unstructured":"Limsuwanchote S, Wungsintaweekul J, Yusakul G, Han JY, Sasaki-Tabata K, Tanaka H, et al. Preparation of a monoclonal antibody against notoginsenoside R1, a distinctive saponin from Panax notoginseng, and its application to indirect competitive ELISA. Planta Med 2014;80:337\u2013342.","journal-title":"Planta Med"}],"container-title":["Chinese Journal of Integrative Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11655-014-1954-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s11655-014-1954-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s11655-014-1954-8","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T19:00:49Z","timestamp":1559415649000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s11655-014-1954-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,12,22]]},"references-count":37,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,6]]}},"alternative-id":["1954"],"URL":"https:\/\/doi.org\/10.1007\/s11655-014-1954-8","relation":{},"ISSN":["1672-0415","1993-0402"],"issn-type":[{"value":"1672-0415","type":"print"},{"value":"1993-0402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,12,22]]}}}