{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T03:30:30Z","timestamp":1777951830113,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T00:00:00Z","timestamp":1773446400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>This study investigated the molecular mechanisms by which ginsenoside Rg3 combined with ranibizumab alleviates diabetic macular edema (DME), focusing on antagonizing ANGPTL4\/VEGF and regulating the NRP\/RhoA pathway to reduce vascular permeability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Transcriptomic sequencing compared blood samples from DME patients and healthy controls, followed by GO\/KEGG enrichment analysis.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , human retinal microvascular endothelial cells (HRMECs) were treated with ginsenoside Rg3 (5, 10, 20\u2009\u03bcM) alone or combined with ranibizumab (1\u2009mg\/mL); cell viability, permeability, and protein expression were assessed.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , diabetic rats received intraperitoneal ginsenoside Rg3 and ranibizumab; ocular pathology, angiogenesis, inflammation, and key protein expression\/activity were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DME patients exhibited significant upregulation of VEGF, ANGPTL4, NRP1 (logFC\u2009=\u20091.9,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.01), and RhoA, associated with angiogenesis\/migration\/inflammation pathways.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , 10\u2009\u03bcM ginsenoside Rg3 optimally reduced HRMEC permeability and suppressed ANGPTL4. Combination therapy further decreased VEGF and ANGPTL4 expression.\n                      <jats:italic>In vivo<\/jats:italic>\n                      , combined treatment significantly reduced retinal edema, angiogenesis, and vascular permeability. It markedly inhibited NRP1 expression and reduced RhoA\/ROCK activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The combination of ginsenoside Rg3 and ranibizumab effectively antagonizes ANGPTL4 and VEGF and regulates the NRP\/RhoA pathway, significantly reducing vascular permeability in DME through synergistic action. This provides crucial theoretical support for novel DME combination therapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.70285","type":"journal-article","created":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T08:26:52Z","timestamp":1773476812000},"page":"751-765","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic inhibition of macular vascular permeability in diabetic edema: Ginsenoside Rg3 enhances ranibizumab efficacy by targeting angiopoietin\u2010like protein 4 and vascular endothelial growth factor via neuropilin\/\n                    <scp>RhoA<\/scp>\n                    signaling"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2299-0108","authenticated-orcid":false,"given":"Jiexin","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xingyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)  Hangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanli","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)  Hangzhou 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