{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:18:24Z","timestamp":1790399904291,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,7]],"date-time":"2024-12-07T00:00:00Z","timestamp":1733529600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Retinal neovascularization is a pathological feature of ischemic retinopathy. Current therapeutic approaches are limited, and additional treatment options are needed. This study aims to discover lead compounds from <jats:italic>Salvia substolonifera<\/jats:italic> that inhibit angiogenesis. As a result, an undescribed norditerpene lactone, substolide H (<jats:bold>3<\/jats:bold>), and eight known compounds (<jats:bold>1<\/jats:bold>, <jats:bold>2<\/jats:bold>, and <jats:bold>4<\/jats:bold>\u2013<jats:bold>9<\/jats:bold>) have been isolated. The structure was elucidated using synthetic spectroscopy and electron circular dichroism. Compounds <jats:bold>2<\/jats:bold>, <jats:bold>3<\/jats:bold>, <jats:bold>5<\/jats:bold>, <jats:bold>7<\/jats:bold>, and <jats:bold>9<\/jats:bold> inhibited human umbilical vein endothelial cells (HUVEC) proliferation with IC<jats:sub>50<\/jats:sub> values of 26.47, 6.10, 43.27, 36.81, and 35.11\u00a0\u00b5M, respectively. Compounds <jats:bold>2<\/jats:bold>, <jats:bold>3<\/jats:bold>, and <jats:bold>7<\/jats:bold> inhibited HUVEC migration with IC<jats:sub>50<\/jats:sub> values of 12.48, 8.37, and 7.63\u00a0\u00b5M, respectively. Further studies have shown that the substolide H (<jats:bold>3<\/jats:bold>) suppresses tube formation in human umbilical vein endothelial cells and that intravitreous administration suppresses retinal neovascularization in oxygen\u2010induced retinopathy mice. Turning to its mechanism of action, we have shown that the anti\u2010angiogenic effect of the substolide H may be through the downregulation of vascular endothelial growth factor expression and the phosphorylation of VEGFR2, ERK1\/2, and protein kinase B. Our study represents the first report of these anti\u2010angiogenic compounds from this plant, and substolide H may be a potential candidate for the treatment of retinal neovascularization.<\/jats:p>","DOI":"10.1002\/cbdv.202401427","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T03:14:41Z","timestamp":1733109281000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Phytochemicals From <i>Salvia substolonifera<\/i> With Anti\u2010Angiogenic Properties and Substolide H Decreased Oxygen\u2010Induced Retinal Neovascularization"],"prefix":"10.1002","volume":"22","author":[{"given":"Zhipeng","family":"Zhong","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meilin","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaojie","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2984-486X","authenticated-orcid":false,"given":"Jianyong","family":"Dong","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1586\/eop.13.17"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12886-021-01964-w"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/07853890.2022.2064541"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04482"},{"key":"e_1_2_8_6_1","first-page":"862","article-title":"CCR7\/p\u2010ERK1\/2\/VEGF Signaling Promotes Retinal Neovascularization in a Mouse Model of Oxygen\u2010Induced Retinopathy","volume":"10","author":"Yuan L. 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