{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T23:54:09Z","timestamp":1789430049306,"version":"build-2803163510"},"reference-count":102,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,30]],"date-time":"2025-03-30T00:00:00Z","timestamp":1743292800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Diabetic retinopathy (DR) is a significant microvascular consequence of diabetes mellitus (DM), resulting in visual impairment and blindness. Controlling hyperglycemia is essential for avoiding and alleviating diabetic retinopathy. Nutrients and natural compounds possessing hypoglycemic characteristics present promising supplementary approaches to conventional therapies. This review assesses the influence of nutrients and natural substances on glycemic regulation and their possible effects on diabetic retinopathy. Goal: To investigate and consolidate knowledge about nutrients and natural compounds exhibiting hypoglycemic properties and their processes in the prevention and management of diabetic retinopathy. Approaches: Extensive reviews were conducted on pertinent studies from databases including PubMed, Scopus, and Web of Science. Selection criteria encompassed papers that examined natural substances, nutrients, or dietary supplements exhibiting effects on blood glucose levels and pathways associated to diabetic retinopathy. Principal findings were encapsulated according to their mechanisms, efficacy, and safety. Outcomes: Numerous foods, including omega-3 fatty acids, vitamin D, and polyphenols (e.g., curcumin, resveratrol), have hypoglycemic properties by improving insulin sensitivity and diminishing oxidative stress. Natural substances like berberine, quercetin, and flavonoids demonstrate analogous effects, influencing pathways associated with inflammation, advanced glycation end products (AGEs), and angiogenesis, which are critical factors in the evolution of diabetic retinopathy (DR). The synergistic benefits of integrating natural medicines with conventional antidiabetic medications may enhance glycemic control and reduce retinal damage. The safety profiles of these therapies are predominantly positive; nonetheless, clinical trials are still constrained in both breadth and scale. Conclusions: Nutrients and natural compounds are promising supplementary approaches for glycemic regulation and the therapy of diabetic retinopathy. Additional research, encompassing extensive clinical studies, is required to substantiate their efficacy, determine optimal dose, and verify long-term safety. The use of these natural substances into clinical practice may improve comprehensive management of diabetes and associated consequences.<\/jats:p>","DOI":"10.3390\/nu17071207","type":"journal-article","created":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T01:59:36Z","timestamp":1743386376000},"page":"1207","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Nutrients and Natural Substances for Hypoglycemic Effects and Management in Diabetic Retinopathy"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-6807-9455","authenticated-orcid":false,"given":"Francesco","family":"Cappellani","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3074-4508","authenticated-orcid":false,"given":"Roberta","family":"Foti","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, A.O.U. \u201cPoliclinico San Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3655-4307","authenticated-orcid":false,"given":"Giulia","family":"Malaguarnera","sequence":"additional","affiliation":[{"name":"Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, 00166 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7938-876X","authenticated-orcid":false,"given":"Fabiana","family":"D\u2019Esposito","sequence":"additional","affiliation":[{"name":"Imperial College Ophthalmic Research Group (ICORG) Unit, Imperial College, 153-173 Marylebone Rd., London NW1 5QH, UK"},{"name":"Department of Neurosciences, Reproductive Sciences and Dentistry, University of Naples Federico II, Via Pansini 5, 80131 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Musumeci","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Rapisarda","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell\u2019Universit\u00e0, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Tognetto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8424-0068","authenticated-orcid":false,"given":"Caterina","family":"Gagliano","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Enna \u201cKore\u201d, Piazza dell\u2019Universit\u00e0, 94100 Enna, Italy"},{"name":"Mediterranean Foundation \u201cG.B. Morgagni\u201d, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-5545","authenticated-orcid":false,"given":"Marco","family":"Zeppieri","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Health Sciences, University of Trieste, 34127 Trieste, Italy"},{"name":"Department of Ophthalmology, University Hospital of Udine, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/s41574-022-00690-7","article-title":"The burden and risks of emerging complications of diabetes mellitus","volume":"18","author":"Tomic","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1883","DOI":"10.2337\/db24-0107","article-title":"Deciphering the Connection Between Microvascular Damage and Neurodegeneration in Early Diabetic Retinopathy","volume":"73","author":"Yang","year":"2024","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1580","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":"ref_5","doi-asserted-by":"crossref","unstructured":"Yang, Z., Tan, T.E., Shao, Y., Wong, T.Y., and Li, X. (2022). Classification of diabetic retinopathy: Past, present and future. Front. Endocrinol., 13.","DOI":"10.3389\/fendo.2022.1079217"},{"key":"ref_6","first-page":"CD013775","article-title":"Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy","volume":"2","author":"Perais","year":"2023","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1615","DOI":"10.2337\/diabetes.54.6.1615","article-title":"The pathobiology of diabetic complications: A unifying mechanism","volume":"54","author":"Brownlee","year":"2005","journal-title":"Diabetes"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Bryl, A., Mrugacz, M., Falkowski, M., and Zorena, K. (2022). The Effect of Diet and Lifestyle on the Course of Diabetic Retinopathy\u2014A Review of the Literature. Nutrients, 14.","DOI":"10.3390\/nu14061252"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Garcia-Medina, J.J., Rubio-Velazquez, E., Foulquie-Moreno, E., Casaroli-Marano, R.P., Pinazo-Duran, M.D., Zanon-Moreno, V., and Del-Rio-Vellosillo, M. (2020). Update on the Effects of Antioxidants on Diabetic Retinopathy: In Vitro Experiments, Animal Studies and Clinical Trials. Antioxidants, 9.","DOI":"10.3390\/antiox9060561"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Matos, A.L., Bruno, D.F., Ambr\u00f3sio, A.F., and Santos, P.F. (2020). The Benefits of Flavonoids in Diabetic Retinopathy. Nutrients, 12.","DOI":"10.3390\/nu12103169"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Fanaro, G.B., Marques, M.R., Calaza KD, C., Brito, R., Pessoni, A.M., Mendon\u00e7a, H.R., Lemos DE, A., de Brito Alves, J.L., de Souza, E.L., and Cavalcanti Neto, M.P. (2023). New Insights on Dietary Polyphenols for the Management of Oxidative Stress and Neuroinflammation in Diabetic Retinopathy. Antioxidants, 12.","DOI":"10.3390\/antiox12061237"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1097\/IAE.0000000000003745","article-title":"Omega-3 Fatty Acids Are Associated with Decreased Presence and Severity of Diabetic Retinopathy: A Combined Analysis of MESA and GOLDR Cohorts","volume":"43","author":"Weir","year":"2023","journal-title":"Retina"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, X., Liu, Y., Zheng, Y., Wang, P., and Zhang, Y. (2018). The Effect of Vitamin D Supplementation on Glycemic Control in Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis. Nutrients, 10.","DOI":"10.3390\/nu10030375"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wang, W., and Lo, A.C.Y. (2018). Diabetic Retinopathy: Pathophysiology and Treatments. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19061816"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Kang, Q., and Yang, C. (2020). Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications. Redox Biol., 37.","DOI":"10.1016\/j.redox.2020.101799"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"6651","DOI":"10.3390\/cimb45080420","article-title":"Oxidative Stress in Type 2 Diabetes: Impacts from Pathogenesis to Lifestyle Modifications","volume":"45","author":"Caturano","year":"2023","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Haydinger, C.D., Oliver, G.F., Ashander, L.M., and Smith, J.R. (2023). Oxidative Stress and Its Regulation in Diabetic Retinopathy. Antioxidants, 12.","DOI":"10.3390\/antiox12081649"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1080\/10715760310001604189","article-title":"Diabetes-induced activation of nuclear transcriptional factor in the retina, and its inhibition by antioxidants","volume":"37","author":"Kowluru","year":"2003","journal-title":"Free Radic. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yue, T., Shi, Y., Luo, S., Weng, J., Wu, Y., and Zheng, X. (2022). The role of inflammation in immune system of diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1055087"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1007\/s10792-020-01463-9","article-title":"Comparison of inflammatory cytokines levels in the aqueous humor with diabetic retinopathy","volume":"40","author":"Zhang","year":"2020","journal-title":"Int. Ophthalmol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.preteyeres.2011.05.002","article-title":"Inflammation in diabetic retinopathy","volume":"30","author":"Tang","year":"2011","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1007\/s12177-013-9104-7","article-title":"Advanced glycation end products and diabetic retinopathy","volume":"5","author":"Sharma","year":"2013","journal-title":"J. Ocul. Biol. Dis. Inform."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.cmet.2018.08.014","article-title":"The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality","volume":"28","author":"Chaudhuri","year":"2018","journal-title":"Cell Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1159\/000491897","article-title":"Involvement of Advanced Glycation End Products in the Pathogenesis of Diabetic Retinopathy","volume":"48","author":"Xu","year":"2018","journal-title":"Cell. Physiol. Biochem. Int. J. Exp. Cell. Physiol. Biochem. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3921","DOI":"10.3889\/oamjms.2019.759","article-title":"Inhibition of Receptor for Advanced Glycation End Products as New Promising Strategy Treatment in Diabetic Retinopathy","volume":"7","author":"Saleh","year":"2019","journal-title":"Open Access Maced. J. Med. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Lee, J., Yun, J.-S., and Ko, S.-H. (2022). Advanced Glycation End Products and Their Effect on Vascular Complications in Type 2 Diabetes Mellitus. Nutrients, 14.","DOI":"10.3390\/nu14153086"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"104924","DOI":"10.1016\/j.phrs.2020.104924","article-title":"Hypoxia-inducible factor-1\u03b1: A promising therapeutic target for vasculopathy in diabetic retinopathy","volume":"159","author":"Li","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rezzola, S., Loda, A., Corsini, M., Semeraro, F., Annese, T., Presta, M., and Ribatti, D. (2020). Angiogenesis-Inflammation Cross Talk in Diabetic Retinopathy: Novel Insights From the Chick Embryo Chorioallantoic Membrane\/Human Vitreous Platform. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.581288"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"108498","DOI":"10.1016\/j.neuropharm.2021.108498","article-title":"Targeted pharmacotherapy against neurodegeneration and neuroinflammation in early diabetic retinopathy","volume":"187","author":"Rolev","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Dionysopoulou, S., Wikstrom, P., Walum, E., Georgakis, S., and Thermos, K. (2024). Investigation of the Effects of a Novel NOX2 Inhibitor, GLX7013170, against Glutamate Excitotoxicity and Diabetes Insults in the Retina. Pharmaceuticals, 17.","DOI":"10.3390\/ph17030393"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"dmm050174","DOI":"10.1242\/dmm.050174","article-title":"IL-33 regulates M\u00fcller cell-mediated retinal inflammation and neurodegeneration in diabetic retinopathy","volume":"16","author":"Augustine","year":"2023","journal-title":"Dis. Models Mech."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E2655","DOI":"10.1073\/pnas.1522014113","article-title":"Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus","volume":"113","author":"Sohn","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.preteyeres.2004.06.002","article-title":"The role of omega-3 long-chain polyunsaturated fatty acids in health and disease of the retina","volume":"24","author":"SanGiovanni","year":"2005","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"108440","DOI":"10.1016\/j.pharmthera.2023.108440","article-title":"The essential role of docosahexaenoic acid and its derivatives for retinal integrity","volume":"247","author":"Swinkels","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"101089","DOI":"10.1016\/j.eclinm.2021.101089","article-title":"Serum \u03c9-6\/\u03c9-3 polyunsaturated fatty acids ratio and diabetic retinopathy: A propensity score matching based case-control study in China","volume":"39","author":"Zhao","year":"2021","journal-title":"eClinicalMedicine"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Tikhonenko, M., Lydic, T.A., Opreanu, M., Li Calzi, S., Bozack, S., McSorley, K.M., Sochacki, A.L., Faber, M.S., Hazra, S., and Duclos, S. (2013). N-3 polyunsaturated Fatty acids prevent diabetic retinopathy by inhibition of retinal vascular damage and enhanced endothelial progenitor cell reparative function. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055177"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e36","DOI":"10.1038\/nutd.2012.10","article-title":"Omega-3 polyunsaturated fatty acids preserve retinal function in type 2 diabetic mice","volume":"2","author":"Sapieha","year":"2012","journal-title":"Nutr. Diabetes"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"D\u00e1tilo, M.N., Sant\u2019Ana, M.R., Formigari, G.P., Rodrigues, P.B., de Moura, L.P., da Silva, A.S.R., Ropelle, E.R., Pauli, J.R., and Cintra, D.E. (2018). Omega-3 from Flaxseed Oil Protects Obese Mice Against Diabetic Retinopathy Through GPR120 Receptor. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-32553-5"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1016\/j.ophtha.2023.11.030","article-title":"ASCEND-Eye: Effects of Omega-3 Fatty Acids on Diabetic Retinopathy","volume":"131","author":"Sammons","year":"2024","journal-title":"Ophthalmology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2226","DOI":"10.1001\/jama.2017.1926","article-title":"Dietary Intake of Omega-3 Fatty Acids From Fish and Risk of Diabetic Retinopathy","volume":"317","author":"Chew","year":"2017","journal-title":"JAMA"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Sala-Vila, A., Vinagre, I., Cof\u00e1n, M., L\u00e1zaro, I., Al\u00e9-Chilet, A., Barraso, M., Hernandez, T., Harris, W.S., Zarranz-Ventura, J., and Ortega, E. (2025). Blood omega-3 biomarkers, diabetic retinopathy and retinal vessel status in patients with type 1 diabetes. Eye.","DOI":"10.1038\/s41433-025-03705-5"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gverovi\u0107 Antunica, A., Znaor, L., Ivankovi\u0107, M., Puzovi\u0107, V., Markovi\u0107, I., and Ka\u0161telan, S. (2023). Vitamin D and Diabetic Retinopathy. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241512014"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e3447","DOI":"10.1002\/dmrr.3447","article-title":"Protective role of vitamin D against oxidative stress in diabetic retinopathy","volume":"37","author":"Valle","year":"2021","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8193523","DOI":"10.1155\/2018\/8193523","article-title":"Vitamin D3 Protects against Diabetic Retinopathy by Inhibiting High-Glucose-Induced Activation of the ROS\/TXNIP\/NLRP3 Inflammasome Pathway","volume":"2018","author":"Lu","year":"2018","journal-title":"J. Diabetes Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1167\/iovs.06-1210","article-title":"Calcitriol is a potent inhibitor of retinal neovascularization","volume":"48","author":"Albert","year":"2007","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1016\/j.diabres.2012.09.028","article-title":"The impact of 1,25-dihydroxy vitamin D3 on the expressions of vascular endothelial growth factor and transforming growth factor-\u03b2\u2081 in the retinas of rats with diabetes","volume":"98","author":"Ren","year":"2012","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"112023","DOI":"10.1016\/j.yexcr.2020.112023","article-title":"Protection by vitamin D against high-glucose-induced damage in retinal pigment epithelial cells","volume":"392","author":"Tohari","year":"2020","journal-title":"Exp. Cell Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/j.diabres.2013.03.008","article-title":"Vitamin D reduces deposition of advanced glycation end-products in the aortic wall and systemic oxidative stress in diabetic rats","volume":"100","author":"Salum","year":"2013","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1089\/gtmb.2019.0037","article-title":"The Impact of Vitamin D Receptor Gene Polymorphisms on the Susceptibility of Diabetic Vascular Complications: A Meta-Analysis","volume":"23","author":"Song","year":"2019","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"S39","DOI":"10.1016\/j.jcjo.2017.09.026","article-title":"Relationship between vitamin D deficiency and diabetic retinopathy: A meta-analysis","volume":"52","author":"Zhang","year":"2017","journal-title":"Can. J. Ophthalmol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Luo, B.A., Gao, F., and Qin, L.L. (2017). The Association between Vitamin D Deficiency and Diabetic Retinopathy in Type 2 Diabetes: A Meta-Analysis of Observational Studies. Nutrients, 9.","DOI":"10.3390\/nu9030307"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"459","DOI":"10.20344\/amp.12890","article-title":"Association between Serum Vitamin D and Diabetic Retinopathy in Portuguese Patients with Type 1 Diabetes","volume":"33","author":"Lopes","year":"2020","journal-title":"Acta Med. Port."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1024\/0300-9831\/a000673","article-title":"Vitamin D3 supplementation improves glycemic control in type 2 diabetic patients: Results from an Italian clinical trial","volume":"92","author":"Derosa","year":"2022","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"161","DOI":"10.4274\/tjps.galenos.2021.62357","article-title":"Vitamin D with Calcium Supplementation Managing Glycemic Control with HbA1c and Improve Quality of Life in Patients with Diabetes","volume":"19","author":"Mehta","year":"2022","journal-title":"Turk. J. Pharm. Sci."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"E26","DOI":"10.1017\/S0029665121000276","article-title":"The effects of vitamin D3 supplementation on insulin resistance and glycaemic control in individuals at high risk of type 2 diabetes: A systematic review and meta\u2013analysis","volume":"80","author":"McFadden","year":"2021","journal-title":"Proc. Nutr. Soc."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Wang, X., Qi, Y., and Zheng, H. (2022). Dietary Polyphenol, Gut Microbiota, and Health Benefits. Antioxidants, 11.","DOI":"10.3390\/antiox11061212"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"117350","DOI":"10.1016\/j.lfs.2020.117350","article-title":"Attenuation of diabetic retinopathy and neuropathy by resveratrol: Review on its molecular mechanisms of action","volume":"245","author":"Ahmad","year":"2020","journal-title":"Life Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1016\/j.exer.2018.11.023","article-title":"Resveratrol exhibits an effect on attenuating retina inflammatory condition and damage of diabetic retinopathy via PON1","volume":"181","author":"Chen","year":"2019","journal-title":"Exp. Eye Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"174167","DOI":"10.1016\/j.ejphar.2021.174167","article-title":"Effects of trans-resveratrol on type 1 diabetes-induced up-regulation of apoptosis and mitogen-activated protein kinase signaling in retinal pigment epithelium of Dark Agouti rats","volume":"904","author":"Kittaneh","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1007\/s11064-015-1793-9","article-title":"Resveratrol Prevents Retinal Dysfunction by Regulating Glutamate Transporters, Glutamine Synthetase Expression and Activity in Diabetic Retina","volume":"41","author":"Zeng","year":"2016","journal-title":"Neurochem. Res."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Gonzalez-Perez, J., Lopera-Echavarr\u00eda, A.M., Arevalo-Alquichire, S., Araque-Mar\u00edn, P., and Londo\u00f1o, M.E. (2024). Development of a Resveratrol Nanoformulation for the Treatment of Diabetic Retinopathy. Materials, 17.","DOI":"10.3390\/ma17061420"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4103\/ejpi.EJPI-D-23-00035","article-title":"Protective Effect of Curcumin on the Tight Junction Integrity and Cellular Senescence in Human Retinal Pigment Epithelium of Early Diabetic Retinopathy","volume":"67","author":"Cheng","year":"2024","journal-title":"J. Physiol. Investig."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/s13273-021-00144-7","article-title":"Curcumin suppresses oxidative stress via regulation of ROS\/NF-\u03baB signaling pathway to protect retinal vascular endothelial cell in diabetic retinopathy","volume":"17","author":"Huang","year":"2021","journal-title":"Mol. Cell. Toxicol."},{"key":"ref_64","unstructured":"Yao, B., Xin, Z.K., and Wang, D. (2023). The effect of curcumin on on intravitreal proinflammatory cytokines, oxidative stress markers, and vascular endothelial growth factor in an experimental model of diabetic retinopathy. J. Physiol. Pharmacol., 74."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"639","DOI":"10.2515\/therapie:2004110","article-title":"Photo-irradiated curcumin supplementation in streptozotocin-induced diabetic rats: Effect on lipid peroxidation","volume":"59","author":"Mahesh","year":"2004","journal-title":"Therapie"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13098-019-0437-7","article-title":"The effect of curcumin supplementation on anthropometric indices, insulin resistance and oxidative stress in patients with type 2 diabetes: A randomized, double-blind clinical trial","volume":"11","author":"Hodaei","year":"2019","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"8278744","DOI":"10.1155\/2022\/8278744","article-title":"The Effect of Curcumin on Lipid Profile and Glycemic Status of Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis","volume":"2022","author":"Tian","year":"2022","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Panknin, T.M., Howe, C.L., Hauer, M., Bucchireddigari, B., Rossi, A.M., and Funk, J.L. (2023). Curcumin Supplementation and Human Disease: A Scoping Review of Clinical Trials. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054476"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Wang, L., Xu, J., Yu, T., Wang, H., Cai, X., and Sun, H. (2023). Efficacy and safety of curcumin in diabetic retinopathy: A protocol for systematic review and meta-analysis. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0282866"},{"key":"ref_70","first-page":"153","article-title":"The effect of curcumin-piperine on cardiometabolic, inflammatory and oxidative stress factors and macular vascular density in optical coherence tomography angiography (OCTA) in patients with non-proliferative diabetic retinopathy: Study protocol for a randomized, double-blind controlled trial","volume":"13","author":"Amini","year":"2023","journal-title":"Avicenna J. Phytomed."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1743-7075-8-18","article-title":"Onion peel extracts ameliorate hyperglycemia and insulin resistance in high fat diet\/streptozotocin-induced diabetic rats","volume":"8","author":"Jung","year":"2011","journal-title":"Nutr. Metab."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1167\/iovs.08-2642","article-title":"Baicalein reduces inflammatory process in a rodent model of diabetic retinopathy","volume":"50","author":"Yang","year":"2009","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1474","DOI":"10.3945\/jn.113.177212","article-title":"Higher dietary flavonol intake is associated with lower incidence of type 2 diabetes","volume":"143","author":"Jacques","year":"2013","journal-title":"J. Nutr."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"3533","DOI":"10.1093\/jn\/nxab269","article-title":"Higher Habitual Flavonoid Intakes Are Associated with a Lower Incidence of Diabetes","volume":"151","author":"Bondonno","year":"2021","journal-title":"J. Nutr."},{"key":"ref_75","first-page":"2057333","article-title":"Hypoglycemic Effects of Plant Flavonoids: A Review","volume":"2021","author":"Darmarajan","year":"2021","journal-title":"Evid. Based Complement. Altern. Med."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4316","DOI":"10.7150\/ijbs.62868","article-title":"Berberine improves insulin-induced diabetic retinopathy through exclusively suppressing Akt\/mTOR-mediated HIF-1\u03b1\/VEGF activation in retina endothelial cells","volume":"17","author":"Wang","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_77","first-page":"4227","article-title":"Berberine protects against diabetic retinopathy by inhibiting cell apoptosis via deactivation of the NF-\u03baB signaling pathway","volume":"22","author":"Zhai","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Fang, W., Huang, X., Wu, K., Zong, Y., Yu, J., Xu, H., Shi, J., Wei, J., Zhou, X., and Jiang, C. (2022). Activation of the GABA-alpha receptor by berberine rescues retinal ganglion cells to attenuate experimental diabetic retinopathy. Front. Mol. Neurosci., 15.","DOI":"10.3389\/fnmol.2022.930599"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"2074610","DOI":"10.1155\/2021\/2074610","article-title":"The Effect of Berberine on Metabolic Profiles in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials","volume":"2021","author":"Guo","year":"2021","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_80","doi-asserted-by":"crossref","unstructured":"Xie, W., Su, F., Wang, G., Peng, Z., Xu, Y., Zhang, Y., Xu, N., Hou, K., Hu, Z., and Chen, Y. (2022). Glucose-lowering effect of berberine on type 2 diabetes: A systematic review and meta-analysis. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1015045"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.4103\/1673-5374.301027","article-title":"Quercetin protects against diabetic retinopathy in rats by inducing heme oxygenase-1 expression","volume":"16","author":"Chai","year":"2021","journal-title":"Neural Regen. Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"42","DOI":"10.18240\/ijo.2021.01.06","article-title":"Effects of quercetin on diabetic retinopathy and its association with NLRP3 inflammasome and autophagy","volume":"14","author":"Li","year":"2021","journal-title":"Int. J. Ophthalmol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.nutres.2023.12.003","article-title":"Quercetin protects against hyperglycemia-induced retinopathy in Sprague Dawley rats by regulating the gut-retina axis and nuclear factor erythroid-2-related factor 2 pathway","volume":"122","author":"Liu","year":"2024","journal-title":"Nutr. Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.biopha.2018.10.152","article-title":"Antidiabetic and antihyperlipidemic effects of ethanolic Ferula assa-foetida oleo-gum-resin extract in streptozotocin-induced diabetic wistar rats","volume":"110","author":"Latifi","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1007\/s00595-019-1761-0","article-title":"The protective effect of epigallocatechin 3-gallate on mouse pancreatic islets via the Nrf2 pathway","volume":"49","author":"Wada","year":"2019","journal-title":"Surg. Today"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.yexcr.2019.04.014","article-title":"Epigallocatechin-3-gallate stimulates autophagy and reduces apoptosis levels in retinal M\u00fcller cells under high-glucose conditions","volume":"380","author":"Wang","year":"2019","journal-title":"Exp. Cell Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1136\/bjophthalmol-2016-309814","article-title":"Putative protective role of lutein and zeaxanthin in diabetic retinopathy","volume":"101","author":"Neelam","year":"2017","journal-title":"Br. J. Ophthalmol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40662-017-0088-4","article-title":"Effect of carotenoids dietary supplementation on macular function in diabetic patients","volume":"4","author":"Moschos","year":"2017","journal-title":"Eye Vis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1645","DOI":"10.1167\/iovs.07-0764","article-title":"Beneficial effect of zeaxanthin on retinal metabolic abnormalities in diabetic rats","volume":"49","author":"Kowluru","year":"2008","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Lem, D.W., Gierhart, D.L., and Davey, P.G. (2021). A Systematic Review of Carotenoids in the Management of Diabetic Retinopathy. Nutrients, 13.","DOI":"10.3390\/nu13072441"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Anzar, C.A., Joseph, M.V., Sundaram, R., Vadiraj, G.B., Prasad, C.P., Eranimose, B., and Jagadeesh, S. (2023). Safety Assessment of Lutein and Zeaxanthin Supplementation and Its Effects on Blood Glucose Levels, Kidney Functions, Liver Functions and Bone Health\u2014A Randomized, Double-Blind, Placebo-Controlled Clinical Study. medRxiv.","DOI":"10.1101\/2023.09.22.23295947"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13098-019-0431-0","article-title":"Curcumin combined with metformin decreases glycemia and dyslipidemia, and increases paraoxonase activity in diabetic rats","volume":"11","author":"Roxo","year":"2019","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2136","DOI":"10.1016\/j.biopha.2018.11.064","article-title":"Curcumin augments the cardioprotective effect of metformin in an experimental model of type I diabetes mellitus; Impact of Nrf2\/HO-1 and JAK\/STAT pathways","volume":"109","author":"Abdelsamia","year":"2019","journal-title":"Biomed. Pharmacother.=Biomed. Pharmacother."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Xie, T., Chen, X., Chen, W., Huang, S., Peng, X., Tian, L., Wu, X., and Huang, Y. (2021). Curcumin is a Potential Adjuvant to Alleviates Diabetic Retinal Injury via Reducing Oxidative Stress and Maintaining Nrf2 Pathway Homeostasis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.796565"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"712","DOI":"10.1016\/j.metabol.2008.01.013","article-title":"Efficacy of berberine in patients with type 2 diabetes mellitus","volume":"57","author":"Yin","year":"2008","journal-title":"Metab. Clin. Exp."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Khadke, S., Mandave, P., Kuvalekar, A., Pandit, V., Karandikar, M., and Mantri, N. (2020). Synergistic Effect of Omega-3 Fatty Acids and Oral-Hypoglycemic Drug on Lipid Normalization through Modulation of Hepatic Gene Expression in High Fat Diet with Low Streptozotocin-Induced Diabetic Rats. Nutrients, 12.","DOI":"10.3390\/nu12123652"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"261","DOI":"10.7570\/jomes23080","article-title":"Combination of Metformin and Epigallocatechin-3-Gallate Lowers Cortisol, 11\u03b2-Hydroxysteroid Dehydrogenase Type 1, and Blood Glucose Levels in Sprague Dawley Rats with Obesity and Diabetes","volume":"33","author":"Atsarina","year":"2024","journal-title":"J. Obes. Metab. Syndr."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"8319","DOI":"10.1021\/acs.jafc.7b02531","article-title":"Dietary Flavonoids and Acarbose Synergistically Inhibit \u03b1-Glucosidase and Lower Postprandial Blood Glucose","volume":"65","author":"Zhang","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_99","first-page":"325","article-title":"Anti-diabetic effect of cotreatment with resveratrol and pioglitazone in diabetic rats","volume":"27","author":"Tamimi","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Valdes, M., Calzada, F., Mart\u00ednez-Sol\u00eds, J., and Mart\u00ednez-Rodr\u00edguez, J. (2023). Antihyperglycemic Effects of Annona cherimola Miller and the Flavonoid Rutin in Combination with Oral Antidiabetic Drugs on Streptozocin-Induced Diabetic Mice. Pharmaceuticals, 16.","DOI":"10.3390\/ph16010112"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Knop, J., Misaka, S., Singer, K., Hoier, E., M\u00fcller, F., Glaeser, H., K\u00f6nig, J., and Fromm, M.F. (2015). Inhibitory Effects of Green Tea and (-)-Epigallocatechin Gallate on Transport by OATP1B1, OATP1B3, OCT1, OCT2, MATE1, MATE2-K and P-Glycoprotein. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0139370"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1007\/s11418-016-1063-4","article-title":"Naringenin interferes with the anti-diabetic actions of pioglitazone via pharmacodynamic interactions","volume":"71","author":"Yoshida","year":"2017","journal-title":"J. Nat. Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1207\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:05:43Z","timestamp":1760029543000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/17\/7\/1207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,30]]},"references-count":102,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["nu17071207"],"URL":"https:\/\/doi.org\/10.3390\/nu17071207","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,30]]}}}