{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T18:49:35Z","timestamp":1781203775767,"version":"3.54.1"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T00:00:00Z","timestamp":1746144000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>This study aimed to evaluate the role of hyperoside in ameliorating the retinal injury of diabetic retinopathy (DR) rats and the dysfunction of retinal endothelial cells (RECs) in high glucose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RECs were cultured in various groups including high glucose and different concentrations of hyperoside. The viability, migration, and tube formation of RECs and the expression of transforming growth factor-beta 1 (TGF-\u03b21)\/micro-RNA 200b (miR-200b)\/vascular endothelial growth factor (VEGF) in each group were assayed. Sprague\u2013Dawley rats were used for DR modeling and were treated with hyperoside. The tissue pathology of the rat retina and the expression of TGF-\u03b21\/miR-200b\/VEGF in the retinal tissues of each group were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Excessive proliferation, migration, and tube formation of RECs were induced by high glucose. The retinal pathological changes and vasculopathy in DR rats were more serious compared with those in normal rats. The expression levels of TGF-\u03b21 and VEGF in the high glucose-induced REC group and in DR rat retina were markedly upregulated, but those of miR-200b were noticeably downregulated. However, hyperoside could significantly inhibit the high glucose-induced overproliferation, migration, and tube formation of RECs, alleviate the retinal injury in DR rats, and reverse the expression of TGF-\u03b21\/miR-200b\/VEGF in the high glucose-induced REC and DR rat retina, dose-dependently.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Hyperoside could ameliorate retinal injury in DR rats and the high glucose-induced dysfunction of RECs by regulating the TGF-\u03b21\/miR-200b\/VEGF pathway.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1556310","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:51:38Z","timestamp":1746186698000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Ameliorative effect and potential mechanism of hyperoside on diabetic retinopathy"],"prefix":"10.3389","volume":"16","author":[{"given":"Xu","family":"Yu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoxiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjun","family":"Miao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijie","family":"Ben","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rongwei","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shimei","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shasha","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoci","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiqiao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"010803","DOI":"10.7189\/jogh.08.010803","article-title":"Prevalence, risk factors and burden of diabetic retinopathy in China: a systematic review and meta-analysis","volume":"8","author":"Song","year":"2018","journal-title":"J Glob Health"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ophtha.2021.04.027","article-title":"Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis","volume":"128","author":"Teo","year":"2021","journal-title":"Ophthalmology"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1077669","article-title":"Diabetic retinopathy: Looking forward to 2030","volume":"13","author":"Tan","year":"2023","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B4","doi-asserted-by":"publisher","first-page":"P66","DOI":"10.1016\/j.ophtha.2019.09.025","article-title":"Diabetic retinopathy preferred practice pattern\u00ae","volume":"127","author":"Flaxel","year":"2020","journal-title":"Ophthalmology"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000019102","article-title":"Traditional chinese medicine for diabetic retinopathy: A systematic review and meta-analysis","volume":"99","author":"Pang","year":"2020","journal-title":"Med (Baltimore)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"5204917","DOI":"10.1155\/2020\/5204917","article-title":"Therapeutic effect of abelmoschus manihot on type 2 diabetic nonproliferative retinopathy and the involvement of VEGF","volume":"2020","author":"Zhao","year":"2020","journal-title":"Evid Based Complement Alternat Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.551766","article-title":"Luo tong formula alleviates diabetic retinopathy in rats through micro-200b target","volume":"11","author":"Pang","year":"2020","journal-title":"Front Pharmacol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01068","article-title":"Traditional uses, chemical constituents, biological properties, clinical settings, and toxicities of abelmoschus manihot L.: A comprehensive review","volume":"11","author":"Luan","year":"2020","journal-title":"Front Pharmacol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.abi4613","article-title":"Transforming growth factor-\u03b21 in regulatory T cell biology","volume":"7","author":"Moreau","year":"2022","journal-title":"Sci Immunol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"9558","DOI":"10.3390\/ijms21249558","article-title":"TGF-\u03b2 Serum levels in diabetic retinopathy patients and the role of anti-VEGF therapy","volume":"21","author":"Bonfiglio","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2023.07.036","article-title":"TGF-\u03b2 signaling in health and disease","volume":"186","author":"Massagu\u00e9","year":"2023","journal-title":"Cell"},{"key":"B12","doi-asserted-by":"publisher","first-page":"105941","DOI":"10.1016\/j.phrs.2021.105941","article-title":"MicroRNA targets and biomarker validation for diabetes-associated cardiac fibrosis","volume":"174","author":"Jin","year":"2021","journal-title":"Pharmacol Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/wrr.13100","article-title":"MicroRNAs involved in human skin burns, wound healing and scarring","volume":"31","author":"Siu","year":"2023","journal-title":"Wound Repair Regen"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1125077","article-title":"Microenvironment commits breast tumor ECs to dedifferentiation by micro-RNA-200-b-3p regulation and extracellular matrix remodeling","volume":"11","author":"Wilkus-Adamczyk","year":"2023","journal-title":"Front Cell Dev Biol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"148874","DOI":"10.1016\/j.gene.2024.148874","article-title":"Exosomal delivery of miR-200b-3p suppresses the growth of hepatocellular carcinoma cells by targeting ERG- and VEGF-mediated angiogenesis","volume":"931","author":"Wang","year":"2024","journal-title":"Gene"},{"key":"B16","doi-asserted-by":"publisher","first-page":"100954","DOI":"10.1016\/j.preteyeres.2021.100954","article-title":"VEGFR1 signaling in retinal angiogenesis and microinflammation","volume":"84","author":"Uemura","year":"2021","journal-title":"Prog Retin Eye Res"},{"key":"B17","doi-asserted-by":"publisher","first-page":"12271","DOI":"10.3390\/ijms252212271","article-title":"M\u00fcller glia co-regulate barrier permeability with endothelial cells in an vitro model of hyperglycemia","volume":"25","author":"Pe\u00f1a","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s00011-021-01518-2","article-title":"PHD2 attenuates high-glucose-induced blood retinal barrier breakdown in human retinal microvascular endothelial cells by regulating the Hif-1\u03b1\/VEGF pathway","volume":"71","author":"Li","year":"2022","journal-title":"Inflammation Res"},{"key":"B19","doi-asserted-by":"publisher","first-page":"25","DOI":"10.14712\/fb2022068010025","article-title":"PLAG1 promotes high glucose-induced angiogenesis and migration of retinal endothelial cells by regulating the wnt\/\u03b2-catenin signalling pathway","volume":"68","author":"Gu","year":"2022","journal-title":"Folia Biol (Praha)"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2021.04.035","article-title":"Transthyretin affects the proliferation and migration of human retinal microvascular endothelial cells in hyperglycemia via hnRNPA2B1","volume":"557","author":"Gu","year":"2021","journal-title":"Biochem Biophys Res Commun"},{"key":"B21","doi-asserted-by":"publisher","first-page":"BSR20201545","DOI":"10.1042\/BSR20201545","article-title":"miR-200-3p suppresses cell proliferation and reduces apoptosis in diabetic retinopathy via blocking the TGF-\u03b22\/Smad pathway","volume":"40","author":"Xue","year":"2020","journal-title":"Biosci Rep"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e22017","article-title":"The pharmacological mechanism of Abelmoschus manihot in the treatment of chronic kidney disease","volume":"9","author":"Wei","year":"2023","journal-title":"Heliyon"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.v36.7","article-title":"Hyperoside: A review on its sources, biological activities, and molecular mechanisms","volume":"36","author":"Wang","year":"2022","journal-title":"Phytother Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00797","article-title":"Hyperoside ameliorates diabetic retinopathy via anti-oxidation, inhibiting cell damage and apoptosis induced by high glucose","volume":"11","author":"Wu","year":"2020","journal-title":"Front Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.18-24567","article-title":"A novel murine model of radiation keratopathy","volume":"59","author":"Harris","year":"2018","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s40662-021-00239-1","article-title":"Neurovascular unit in diabetic retinopathy: pathophysiological roles and potential therapeutical targets","volume":"8","author":"Nian","year":"2021","journal-title":"Eye Vis (Lond)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"17914","DOI":"10.1038\/s41598-020-74919-8","article-title":"TGF-\u03b21 is a regulator of the pyruvate dehydrogenase complex in fibroblasts","volume":"10","author":"Smith","year":"2020","journal-title":"Sci Rep"},{"key":"B28","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1038\/s41419-021-04197-3","article-title":"TDAG51 induces renal interstitial fibrosis through modulation of TGF-\u03b2 receptor 1 in chronic kidney disease","volume":"12","author":"Carlisle","year":"2021","journal-title":"Cell Death Dis"},{"key":"B29","doi-asserted-by":"publisher","first-page":"9085","DOI":"10.3390\/ijms24109085","article-title":"The management of diabetes mellitus using medicinal plants and vitamins","volume":"24","author":"Yedjou","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/ame2.12455","article-title":"Developments in the study of Chinese herbal medicine\u2019s assessment index and action mechanism for diabetes mellitus","volume":"7","author":"Liu","year":"2024","journal-title":"Anim Model Exp Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"106933","DOI":"10.1016\/j.vph.2021.106933","article-title":"Extrinsic and intrinsic factors influencing metabolic memory in type 2 diabetes","volume":"142","author":"Vasishta","year":"2022","journal-title":"Vascul Pharmacol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00201.2022","article-title":"Epigenetic modifications in metabolic memory: What are the memories, and can we erase them","volume":"323","author":"Chen","year":"2022","journal-title":"Am J Physiol Cell Physiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.02.023","article-title":"Calcium dobesilate and micro-vascular diseases","volume":"221","author":"Liu","year":"2019","journal-title":"Life Sci"},{"key":"B34","doi-asserted-by":"publisher","first-page":"9893682","DOI":"10.1155\/2019\/9893682","article-title":"Investigation of the mechanism underlying calcium dobesilate-mediated improvement of endothelial dysfunction and inflammation caused by high glucose","volume":"2019","author":"Zhou","year":"2019","journal-title":"Mediators Inflamm"},{"key":"B35","doi-asserted-by":"publisher","first-page":"112254","DOI":"10.1016\/j.biopha.2021.112254","article-title":"Yiqi Tongluo Fang could preventive and delayed development and formation of diabetic retinopathy through antioxidant and anti-inflammatory effects","volume":"148","author":"Di","year":"2022","journal-title":"BioMed Pharmacother"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.732655","article-title":"Hu-zhang-qing-mai-yin inhibits proliferation of human retinal capillary endothelial cells exposed to high glucose","volume":"12","author":"Yu","year":"2021","journal-title":"Front Pharmacol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s00592-021-01813-8","article-title":"LncRNA THRIL promotes high glucose-induced proliferation and migration of human retina microvascular endothelial cells through enhancing autophagy","volume":"59","author":"Ji","year":"2022","journal-title":"Acta Diabetol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"4510628","DOI":"10.1155\/2020\/4510628","article-title":"High glucose induces the loss of retinal pericytes partly via NLRP3-caspase-1-GSDMD-mediated pyroptosis","volume":"2020","author":"Gan","year":"2020","journal-title":"BioMed Res Int"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1342","DOI":"10.3390\/cells12091342","article-title":"Retinal cell damage in diabetic retinopathy","volume":"12","author":"Zhou","year":"2023","journal-title":"Cells"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1556310\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:51:39Z","timestamp":1746186699000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1556310\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,2]]},"references-count":39,"alternative-id":["10.3389\/fendo.2025.1556310"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1556310","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,2]]},"article-number":"1556310"}}