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Ginsenoside Rb1 (Rb1) has various pharmacological effects on multiple systemic diseases. However, whether Rb1 delays the transition of AKI to CKD and the mechanism are unclear. Here, we discovered that Rb1 could alleviate kidney pathological damage in mice with unilateral ischaemia\/reperfusion injury (uIRI), and it enhanced kidney function, reduced renal fibrosis while increasing microvessel density. By\u00a0virtual screening and molecular docking approaches, we identified vascular endothelial growth factor receptor 2 (VEGFR2) as the principal molecular target of Rb1. Furthermore, we uncovered that Rb1 activated AKT phosphorylation\u2010mediated angiogenesis through binding to VEGFR2, which promoted endothelial tube formation and nitric oxide (NO) release in human umbilical vein endothelial cells (HUVECs) and then relieved the endothelial dysfunction induced by hypoxia\u2010reoxygenation (H\/R). Also, we found that Rb1 activated VEGFR2\/AKT signalling in the kidney tissue of uIRI mice. Knocking down VEGFR2 or inhibiting the AKT signalling pathway can impair the proangiogenic effect of Rb1. Taken together, we demonstrated that Rb1 facilitated renal angiogenesis by activating the VEGFR2\/AKT pathway of endothelial cells, thereby arresting the transition from AKI to CKD, and providing a potential therapeutic strategy for AKI.<\/jats:p>","DOI":"10.1111\/jcmm.70732","type":"journal-article","created":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T10:19:47Z","timestamp":1752920387000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Ginsenoside Rb1 Alleviated the AKI to CKD Transition by Targeting VEGFR2"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-2940-9253","authenticated-orcid":false,"given":"Keying","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan\u2010Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan\u2010Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangning","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan\u2010Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan\u2010Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan\u2010Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan\u2010Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan\u2010Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangmei","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan\u2010Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan\u2010Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine ..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6839-7695","authenticated-orcid":false,"given":"Quan","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Nephrology, First Medical Center of Chinese PLA General Hospital, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Medical Devices and Integrated Traditional Chinese and Western Drug Development for Severe Kidney Diseases Beijing Key Laboratory of Digital Intelligent TCM for the Prevention and Treatment of Pan\u2010Vascular Diseases, Key Disciplines of National Administration of Traditional Chinese Medicine 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