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Here, we investigated the angiogenic effects of (\n                      <jats:italic>S<\/jats:italic>\n                      )\u2010DBZ and (\n                      <jats:italic>R<\/jats:italic>\n                      )\u2010DBZ isomers in vitro and in vivo.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>\n                      A network pharmacology approach was used to predict molecular targets of DBZ. The effects of DBZ isomers on proliferation, migration, and tube formation of human endothelial cells were assessed. For in vivo approaches, the transgenic Tg (\n                      <jats:italic>vegfr2<\/jats:italic>\n                      :GFP) zebrafish and C57BL\/6 mouse Matrigel plug models were used. ELISA and western blots were used to quantitate the release and expression of relevant target molecules and signalling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>DBZ produced a biphasic modulation on proliferation and migration of three types of human endothelial cells. Both DBZ isomers induced tube formation in Matrigel assay and a 12\u2010day co\u2010culture model in vitro. Moreover, DBZ promoted Matrigel neovascularization in mice and partially reversed the vascular disruption in zebrafish induced by PTK787. Mechanistically, DBZ enhanced the cellular levels of VEGF, VEGFR2, and MMP\u20109, as well as activating Akt and MAPK signalling in endothelial cells. Selective inhibition of PI3K and MEK significantly attenuated its angiogenic effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>These data reveal, for the first time, that DBZ promotes multiple key steps of angiogenesis, at least in part through Akt and MAPK signalling pathways, and suggest it may be potentially developed further for treating myocardial infarction and other cardiovascular diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.14714","type":"journal-article","created":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T12:28:07Z","timestamp":1558528087000},"page":"3143-3160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Tanshinol borneol ester, a novel synthetic small molecule angiogenesis stimulator inspired by botanical formulations for angina pectoris"],"prefix":"10.1111","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-5514","authenticated-orcid":false,"given":"Sha","family":"Liao","sequence":"first","affiliation":[{"name":"Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Science and Medicine Northwest University  Xi'an China"},{"name":"Angiogenesis and Chinese Medicine Laboratory, Department of Pharmacology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liwen","family":"Han","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaopu","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine The First Affiliated Hospital of Xi'an Jiaotong University Health Science Center  Xi'an 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Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Science and Medicine Northwest University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youlan","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Science and Medicine Northwest University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Science and Medicine Northwest University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximeng","family":"Kang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Science and Medicine Northwest University  Xi'an China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kechun","family":"Liu","sequence":"additional","affiliation":[{"name":"Biology Institute Qilu University of Technology (Shandong Academy of Sciences)  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tai\u2010ping","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, Faculty of Life Science and Medicine Northwest University  Xi'an China"},{"name":"Angiogenesis and Chinese Medicine Laboratory, Department of Pharmacology University of Cambridge  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao","family":"Li","sequence":"additional","affiliation":[{"name":"MOE Key Laboratory of Bioinformatics and Bioinformatics Division, BNRist\/Department of Automation Tsinghua University  Beijing 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