{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T01:45:28Z","timestamp":1791942328131,"version":"4.3.4"},"reference-count":110,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Methylglyoxal (MG) is a reactive dicarbonyl compound generated mainly as a byproduct of glycolysis. Excess accumulation of MG can promote protein glycation and the formation of advanced glycation end-products (AGEs), which have been associated with oxidative stress, inflammation, mitochondrial dysfunction, and cellular damage. These processes are implicated in the development of several chronic conditions, including diabetes, neurodegenerative disorders, cardiovascular disease, and age-related decline. The glyoxalase system, comprising Glyoxalase I (Glo1) and Glyoxalase II (Glo2), serves as a key cellular defense mechanism that detoxifies MG and helps maintain dicarbonyl homeostasis. Among these enzymes, Glo1 catalyzes the conversion of MG into less reactive intermediates in a glutathione (GSH)-dependent manner. A range of natural compounds and dietary phytochemicals, including sulforaphane, resveratrol, \u03b1-lipoic acid, selenium, vitamin D3, and N-acetylcysteine, have been reported to modulate Glo1 activity through transcriptional regulation, antioxidant effects, or support of intracellular GSH levels. Evidence from preclinical and limited human studies suggests that these compounds may help reduce MG burden and AGE formation, although their effects are often indirect and context-dependent. However, several challenges remain, including variable bioavailability, dose-dependent responses, disease-specific differences in Glo1 regulation, and the lack of standardized biomarkers and adequate clinical validation. This review examines the MG\u2013Glo1 axis as a mechanistic framework linking metabolic stress to disease and evaluates natural compounds as context-dependent modulators of this pathway. By integrating mechanistic insights with emerging in vivo and clinical evidence, this work highlights the potential, while acknowledging the limitations, of targeting Glo1 as a translational strategy for managing glycation-associated disorders.<\/jats:p>","DOI":"10.3390\/life16050822","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:33:54Z","timestamp":1779687234000},"page":"822","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting Glyoxalase-1 Pathway with Natural Compounds: A Translational Strategy to Reduce Dicarbonyl Stress and Prevent Chronic Diseases"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-4189","authenticated-orcid":false,"given":"Masood Alam","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51412, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3066-1312","authenticated-orcid":false,"given":"Hina","family":"Younus","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biotechnology Unit, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Va\u0161kov\u00e1, J., Kov\u00e1\u010dov\u00e1, G., Pudelsk\u00fd, J., Palen\u010d\u00e1r, D., and Mi\u010dkov\u00e1, H. (2025). Methylglyoxal Formation\u2014Metabolic Routes and Consequences. Antioxidants, 14.","DOI":"10.3390\/antiox14020212"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.ijbiomac.2014.01.001","article-title":"Protective Effect of Thymoquinone on Glucose- or Methylglyoxal-Induced Glycation of Superoxide Dismutase","volume":"65","author":"Khan","year":"2014","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Nigro, C., Leone, A., Fiory, F., Prevenzano, I., Nicol\u00f2, A., Mirra, P., Beguinot, F., and Miele, C. (2019). Dicarbonyl Stress at the Crossroads of Healthy and Unhealthy Aging. Cells, 8.","DOI":"10.3390\/cells8070749"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Gonz\u00e1lez, P., Lozano, P., Ros, G., and Solano, F. (2023). Hyperglycemia and Oxidative Stress: An Updated Overview of Their Metabolic Interconnections. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119352"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Morgenstern, J., Campos, M.C., Nawroth, P., and Fleming, T. (2020). The Glyoxalase System\u2014New Insights into an Ancient Metabolism. Antioxidants, 9.","DOI":"10.3390\/antiox9100939"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Aragon\u00e8s, G., Rowan, S., Francisco, S.G., Yang, W., Weinberg, J., Taylor, A., and Bejarano, E. (2020). Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy. Antioxidants, 9.","DOI":"10.3390\/antiox9111062"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Scir\u00e8, A., Cianfruglia, L., Minnelli, C., Romaldi, B., Laudadio, E., Galeazzi, R., Antognelli, C., and Armeni, T. (2022). Glyoxalase 2: A Broader Perspective of the Glyoxalase System. Antioxidants, 11.","DOI":"10.3390\/antiox11112131"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"110663","DOI":"10.1016\/j.biopha.2020.110663","article-title":"Glyoxalase System: Biological Activity, Related Diseases, and Small Molecule Regulators","volume":"131","author":"He","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1042\/CS20220099","article-title":"Methylglyoxal and glyoxalase 1\u2014A metabolic stress pathway-linking hyperglycemia to the unfolded protein response and vascular complications of diabetes","volume":"136","author":"Rabbani","year":"2022","journal-title":"Clin. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"291","DOI":"10.2337\/db13-0316","article-title":"Knockdown of glyoxalase 1 mimics diabetic nephropathy in nondiabetic mice","volume":"63","author":"Giacco","year":"2014","journal-title":"Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1007\/s00125-013-3088-5","article-title":"Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes","volume":"57","author":"Brouwers","year":"2014","journal-title":"Diabetologia"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"238485","DOI":"10.1155\/2014\/238485","article-title":"Role of Methylglyoxal in Alzheimer\u2019s Disease","volume":"2014","author":"Angeloni","year":"2014","journal-title":"BioMed Res. Int."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yang, Z., Zhang, W., Lu, H., and Cai, S. (2022). Methylglyoxal in the Brain: From Glycolytic Metabolite to Signalling Molecule. Molecules, 27.","DOI":"10.3390\/molecules27227905"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1021\/acs.chemrestox.2c00160","article-title":"Methylglyoxal and Its Adducts: Induction, Repair, and Association with Disease","volume":"35","author":"Lai","year":"2022","journal-title":"Chem. Res. Toxicol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1152\/physrev.00001.2019","article-title":"Methylglyoxal, a Highly Reactive Dicarbonyl Compound, in Diabetes, Its Vascular Complications, and Other Age-Related Diseases","volume":"100","author":"Schalkwijk","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/s41419-020-2602-1","article-title":"Molecular mechanisms of methylglyoxal-induced aortic endothelial dysfunction in human vascular endothelial cells","volume":"11","author":"Lee","year":"2020","journal-title":"Cell Death Dis."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Alfarano, M., Pastore, D., Fogliano, V., Schalkwijk, C.G., and Oliviero, T. (2018). The Effect of Sulforaphane on Glyoxalase I Expression and Activity in Peripheral Blood Mononuclear Cells. Nutrients, 10.","DOI":"10.3390\/nu10111773"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7857186","DOI":"10.1155\/2016\/7857186","article-title":"Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician\u2019s Expectation Be Matched by the Reality?","volume":"2016","author":"Houghton","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Xue, M., Rabbani, N., and Thornalley, P.J. (2025). Glyoxalase 1 Inducer, trans-Resveratrol and Hesperetin\u2014Dietary Supplement with Multi-Modal Health Benefits. Antioxidants, 14.","DOI":"10.3390\/antiox14080956"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1017\/S0007114511000316","article-title":"Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients","volume":"106","author":"Laczy","year":"2011","journal-title":"Br. J. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"201","DOI":"10.3892\/mmr.2021.11840","article-title":"N-Acetylcysteine Inhibits Atherosclerosis by Correcting Glutathione-Dependent Methylglyoxal Elimination and dicarbonyl\/oxidative stress in the aorta of diabetic mice","volume":"23","author":"Fang","year":"2021","journal-title":"Mol. Med. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Superti, F., and Russo, R. (2024). Alpha-Lipoic Acid: Biological Mechanisms and Health Benefits. Antioxidants, 13.","DOI":"10.3390\/antiox13101228"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Santel, T., Pflug, G., Hemdan, N.Y., Sch\u00e4fer, A., Hollenbach, M., Buchold, M., Hintersdorf, A., Lindner, I., Otto, A., and Bigl, M. (2008). Curcumin inhibits glyoxalase 1\u2014A possible link to its anti-inflammatory and anti-tumor activity. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0003508"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1766","DOI":"10.1021\/acs.chemrestox.2c00182","article-title":"The Human Glyoxalase Gene Family in Health and Disease","volume":"35","author":"Farrera","year":"2022","journal-title":"Chem. Res. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Distler, M.G., and Palmer, A.A. (2012). Role of Glyoxalase 1 (Glo1) and methylglyoxal (MG) in behavior: Recent advances and mechanistic insights. Front. Genet., 3.","DOI":"10.3389\/fgene.2012.00250"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1042\/bst0311343","article-title":"Glyoxalase I\u2014Structure, function and a critical role in the enzymatic defence against glycation","volume":"31","author":"Thornalley","year":"2003","journal-title":"Biochem. Soc. Trans."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"de Bari, L., Scir\u00e8, A., Minnelli, C., Cianfruglia, L., Kalapos, M.P., and Armeni, T. (2021). Interplay among Oxidative Stress, Methylglyoxal Pathway, and S-Glutathionylation. Antioxidants, 10.","DOI":"10.3390\/antiox10010019"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"102222","DOI":"10.1016\/j.redox.2021.102222","article-title":"Role of glyoxalase 1 in methylglyoxal detoxification\u2014The broad player of psychiatric disorders","volume":"49","author":"Toriumi","year":"2022","journal-title":"Redox Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Giustarini, D., Milzani, A., Dalle-Donne, I., and Rossi, R. (2023). How to Increase Cellular Glutathione. Antioxidants, 12.","DOI":"10.3390\/antiox12051094"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1111\/jdi.13032","article-title":"Glycine increases glyoxalase-1 function by promoting nuclear factor erythroid 2-related factor 2 translocation into the nucleus of kidney cells of streptozotocin-induced diabetic rats","volume":"10","author":"Wang","year":"2019","journal-title":"J. Diabetes Investig."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"108524","DOI":"10.1016\/j.pharmthera.2023.108524","article-title":"Glyoxalase I is a novel target for the prevention of metabolic derangement","volume":"250","author":"Miranda","year":"2023","journal-title":"Pharmacol. Ther."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"5645","DOI":"10.18632\/oncotarget.14232","article-title":"AGEs and Neurodegeneration: The Nrf2\/Glyoxalase-1 Interaction","volume":"8","author":"Mastrocola","year":"2017","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/978-1-0716-0640-7_33","article-title":"Spectrophotometric Method for Determining Glyoxalase 1 Activity in Cerebral Cavernous Malformation (CCM) Disease","volume":"Volume 2152","author":"Antognelli","year":"2020","journal-title":"Methods in Molecular Biology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/10409238.2013.838205","article-title":"Transcriptional Regulation by Hypoxia-Inducible Factors","volume":"49","author":"Dengler","year":"2014","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"BSR20210954","DOI":"10.1042\/BSR20210954","article-title":"Systemic inflammation down-regulates glyoxalase-1 expression: An experimental study in healthy males","volume":"41","author":"Driessen","year":"2021","journal-title":"Biosci. Rep."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101406","DOI":"10.1016\/j.molmet.2021.101406","article-title":"The activity of glyoxylase 1 is regulated by glucose-responsive phosphorylation on Tyr136","volume":"55","author":"Cortizo","year":"2022","journal-title":"Mol. Metab."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1038\/s41398-021-01392-w","article-title":"Glyoxalase I disruption and external carbonyl stress impair mitochondrial function in human induced pluripotent stem cells and derived neurons","volume":"11","author":"Hara","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e52990","DOI":"10.15252\/embr.202152990","article-title":"Glyoxalase 1 knockdown induces age-related \u03b2-cell dysfunction and glucose intolerance in mice","volume":"23","author":"Prevenzano","year":"2022","journal-title":"EMBO Rep."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Mey, J.T., and Haus, J.M. (2018). Dicarbonyl Stress and Glyoxalase-1 in Skeletal Muscle: Implications for Insulin Resistance and Type 2 Diabetes. Front. Cardiovasc. Med., 5.","DOI":"10.3389\/fcvm.2018.00117"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Leone, A., Nigro, C., Nicol\u00f2, A., Prevenzano, I., Formisano, P., Beguinot, F., and Miele, C. (2021). The Dual-Role of Methylglyoxal in Tumor Progression\u2014Novel Therapeutic Approaches. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.645686"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"869","DOI":"10.14348\/molcells.2022.0109","article-title":"Glyoxalase 1 as a Therapeutic Target in Cancer and Cancer Stem Cells","volume":"45","author":"Kim","year":"2022","journal-title":"Mol. Cells"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"120111","DOI":"10.1016\/j.lfs.2021.120111","article-title":"Nrf2\/Keap1\/ARE Signaling: Towards Specific Regulation","volume":"291","author":"Ulasov","year":"2022","journal-title":"Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1016\/j.jnutbio.2015.08.001","article-title":"The Complexity of the Nrf2 Pathway: Beyond the Antioxidant Response","volume":"26","author":"Huang","year":"2015","journal-title":"J. Nutr. Biochem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e00099-20","DOI":"10.1128\/MCB.00099-20","article-title":"The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway","volume":"40","author":"Baird","year":"2020","journal-title":"Mol. Cell. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.ccell.2018.03.022","article-title":"NRF2 and the Hallmarks of Cancer","volume":"34","author":"Chapman","year":"2018","journal-title":"Cancer Cell"},{"key":"ref_46","first-page":"11","article-title":"Phytochemical activators of Nrf2: A review of therapeutic strategies in diabetes","volume":"55","author":"Qin","year":"2022","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"110234","DOI":"10.1016\/j.biopha.2020.110234","article-title":"The therapeutic effect of resveratrol: Focusing on the Nrf2 signaling pathway","volume":"127","author":"Farkhondeh","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Rochel, N. (2022). Vitamin D and Its Receptor from a Structural Perspective. Nutrients, 14.","DOI":"10.3390\/nu14142847"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Carlberg, C. (2022). Vitamin D and Its Target Genes. Nutrients, 14.","DOI":"10.3390\/nu14071354"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Ten\u00f3rio, M.C.D.S., Graciliano, N.G., Moura, F.A., Oliveira, A.C.M., and Goulart, M.O.F. (2021). N-Acetylcysteine (NAC): Impacts on Human Health. Antioxidants, 10.","DOI":"10.3390\/antiox10060967"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Derosa, G., D\u2019Angelo, A., Romano, D., and Maffioli, P. (2016). A Clinical Trial about a Food Supplement Containing \u03b1-Lipoic Acid on Oxidative Stress Markers in Type 2 Diabetic Patients. Int. J. Mol. Sci., 17.","DOI":"10.3390\/ijms17111802"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"918089","DOI":"10.1155\/2015\/918089","article-title":"The combination of N-acetyl cysteine, alpha-lipoic acid, and bromelain shows high anti-inflammatory properties in novel in vivo and in vitro models of endometriosis","volume":"2015","author":"Agostinis","year":"2015","journal-title":"Mediat. Inflamm."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Cianfruglia, L., Morresi, C., Bacchetti, T., Armeni, T., and Ferretti, G. (2020). Protection of Polyphenols against Glyco-Oxidative Stress: Involvement of Glyoxalase Pathway. Antioxidants, 9.","DOI":"10.20944\/preprints202009.0383.v1"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Iova, G.M., Calniceanu, H., Popa, A., Szuhanek, C.A., Marcu, O., Ciavoi, G., and Scrobota, I. (2021). The Antioxidant Effect of Curcumin and Rutin on Oxidative Stress Biomarkers in Experimentally Induced Periodontitis in Hyperglycemic Wistar Rats. Molecules, 26.","DOI":"10.3390\/molecules26051332"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Bouranis, J.A., Wong, C.P., Beaver, L.M., Uesugi, S.L., Papenhausen, E.M., Choi, J., Davis, E.W., Da Silva, A.N., Kalengamaliro, N., and Chaudhary, R. (2023). Sulforaphane Bioavailability in Healthy Subjects Fed a Single Serving of Fresh Broccoli Microgreens. Foods, 12.","DOI":"10.3390\/foods12203784"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1750","DOI":"10.4103\/1673-5374.169613","article-title":"Antiglycative activity of sulforaphane: A new avenue to counteract neurodegeneration?","volume":"10","author":"Angeloni","year":"2015","journal-title":"Neural Regen. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1002\/fsn3.2040","article-title":"The protective effect of sulforaphane on type II diabetes induced by high-fat diet and low-dosage streptozotocin","volume":"9","author":"Tian","year":"2020","journal-title":"Food Sci. Nutr."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"107127","DOI":"10.1016\/j.jff.2025.107127","article-title":"Resveratrol in food systems: Challenges, innovations, and health potential","volume":"136","author":"Bouchard","year":"2026","journal-title":"J. Funct. Foods"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1161\/CIRCULATIONAHA.117.030387","article-title":"Wine and Cardiovascular Health: A Comprehensive Review","volume":"136","author":"Haseeb","year":"2017","journal-title":"Circulation"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e70252","DOI":"10.1002\/mco2.70252","article-title":"Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects","volume":"6","author":"Ren","year":"2025","journal-title":"MedComm"},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Schmidt, B., Ferreira, C., Alves Passos, C.L., Silva, J.L., and Fialho, E. (2020). Resveratrol, Curcumin and Piperine Alter Human Glyoxalase 1 in MCF-7 Breast Cancer Cells. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155244"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Salehi, B., Y\u0131lmaz, Y.B., Antika, G., Boyunegmez Tumer, T., Mahomoodally, M.F., Lobine, D., Akram, M., Riaz, M., Capanoglu, E., and Sharopov, F. (2019). Insights on the Use of \u03b1-Lipoic Acid for Therapeutic Purposes. Biomolecules, 9.","DOI":"10.3390\/biom9080356"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"17937","DOI":"10.1038\/s41598-024-66785-5","article-title":"Taurine, alpha lipoic acid and vitamin B6 ameliorate the reduced developmental competence of immature mouse oocytes exposed to methylglyoxal","volume":"14","author":"Mokhtari","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_64","first-page":"3276958","article-title":"The Effect of 600 mg Alpha-lipoic Acid Supplementation on Oxidative Stress, Inflammation, and RAGE in Older Adults with Type 2 Diabetes Mellitus","volume":"2019","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0140-6736(00)02490-9","article-title":"The importance of selenium to human health","volume":"356","author":"Rayman","year":"2000","journal-title":"Lancet"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Xiong, Y., Huang, Y., Li, L., Liu, Y., Liu, L., Wang, L., Tong, L., Wang, F., and Fan, B. (2023). A Review of Plant Selenium-Enriched Proteins\/Peptides: Extraction, Detection, Bioavailability, and Effects of Processing. Molecules, 28.","DOI":"10.3390\/molecules28031223"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.freeradbiomed.2022.06.004","article-title":"The role of Glutathione Peroxidase-1 in Health and Disease","volume":"188","author":"Handy","year":"2022","journal-title":"Free Radic. Biol. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1089\/ars.2011.4145","article-title":"The role of selenium in inflammation and immunity: From molecular mechanisms to therapeutic opportunities","volume":"16","author":"Huang","year":"2012","journal-title":"Antioxid. Redox Signal."},{"key":"ref_69","first-page":"301","article-title":"Vitamin D Deficiency, Its Role in Health and Disease, and Current Supplementation Recommendations","volume":"117","author":"Pfotenhauer","year":"2017","journal-title":"J. Am. Osteopath. Assoc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.chembiol.2013.12.016","article-title":"Vitamin D metabolism, mechanism of action, and clinical applications","volume":"21","author":"Bikle","year":"2014","journal-title":"Chem. Biol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2537","DOI":"10.1039\/C5FO01560J","article-title":"1,25-Dihydroxyvitamin D increases the gene expression of enzymes protecting from glucolipotoxicity in peripheral blood mononuclear cells and human primary endothelial cells","volume":"7","author":"Kuricova","year":"2016","journal-title":"Food Funct."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s13098-019-0479-x","article-title":"Effects of vitamin D supplementation on advanced glycation end products signaling pathway in T2DM patients: A randomized, placebo-controlled, double blind clinical trial","volume":"11","author":"Omidian","year":"2019","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"107916","DOI":"10.1016\/j.pharmthera.2021.107916","article-title":"The mechanism of action of N-acetylcysteine (NAC): The emerging role of H2S and sulfane sulfur species","volume":"228","author":"Pedre","year":"2021","journal-title":"Pharmacol. Ther."},{"key":"ref_74","first-page":"1202","article-title":"The Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress","volume":"19","author":"Raghu","year":"2021","journal-title":"Curr. Neuropharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Dobariya, P., Xie, W., Rao, S.P., Xie, J., Seelig, D.M., Vince, R., Lee, M.K., and More, S.S. (2024). Deletion of Glyoxalase 1 Exacerbates Acetaminophen-Induced Hepatotoxicity in Mice. Antioxidants, 13.","DOI":"10.3390\/antiox13060648"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.1104\/pp.17.01183","article-title":"Carnosic Acid and Carnosol, Two Major Antioxidants of Rosemary, Act through Different Mechanisms","volume":"175","author":"Loussouarn","year":"2017","journal-title":"Plant Physiol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Habtemariam, S. (2023). Anti-Inflammatory Therapeutic Mechanisms of Natural Products: Insight from Rosemary Diterpenes, Carnosic Acid and Carnosol. Biomedicines, 11.","DOI":"10.3390\/biomedicines11020545"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Iorio, R., Celenza, G., and Petricca, S. (2022). Multi-Target Effects of \u00df-Caryophyllene and Carnosic Acid at the Crossroads of Mitochondrial Dysfunction and Neurodegeneration: From Oxidative Stress to Microglia-Mediated Neuroinflammation. Antioxidants, 11.","DOI":"10.3390\/antiox11061199"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/j.foodchem.2016.11.056","article-title":"Effect of rosmarinic acid and carnosic acid on AGEs formation in vitro","volume":"221","author":"Ou","year":"2017","journal-title":"Food Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2029854","DOI":"10.1155\/2016\/2029854","article-title":"Methylglyoxal Impairs Insulin Secretion of Pancreatic \u03b2-Cells through Increased Production of ROS and Mitochondrial Dysfunction Mediated by Upregulation of UCP2 and MAPKs","volume":"2016","author":"Bo","year":"2016","journal-title":"J. Diabetes Res."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Eguchi, N., Vaziri, N.D., Dafoe, D.C., and Ichii, H. (2021). The Role of Oxidative Stress in Pancreatic \u03b2 Cell Dysfunction in Diabetes. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22041509"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1016\/j.biopha.2018.01.017","article-title":"Isoferulic acid attenuates methylglyoxal-induced apoptosis in INS-1 rat pancreatic \u03b2-cell through mitochondrial survival pathways and increasing glyoxalase-1 activity","volume":"101","author":"Meeprom","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.tem.2025.08.007","article-title":"Biliverdin reductase-A is a key modulator in insulin signaling and metabolism","volume":"37","author":"Tramutola","year":"2025","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1007\/s40120-018-0091-2","article-title":"Parkinson\u2019s Disease, the Dopaminergic Neuron and Gammahydroxybutyrate","volume":"7","author":"Mamelak","year":"2018","journal-title":"Neurol. Ther."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Mari\u00f1o, L., Uceda, A.B., Leal, F., and Adrover, M. (2024). Insight into the Effect of Methylglyoxal on the Conformation, Function, and Aggregation Propensity of \u03b1-Synuclein. Chemistry, 30.","DOI":"10.1002\/chem.202400890"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1007\/s00018-010-0483-7","article-title":"Alpha-synuclein deficiency leads to increased glyoxalase I expression and glycation stress","volume":"68","author":"Kurz","year":"2011","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s40659-024-00572-4","article-title":"Depression like-behavior and memory loss induced by methylglyoxal is associated with tryptophan depletion and oxidative stress: A new in vivo model of neurodegeneration","volume":"57","author":"Samsuzzaman","year":"2024","journal-title":"Biol. Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/s43587-021-00150-3","article-title":"Molecular Damage in Aging","volume":"1","author":"Gladyshev","year":"2021","journal-title":"Nat. Aging"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.matbio.2010.04.004","article-title":"Methylglyoxal-modified collagen promotes myofibroblast differentiation","volume":"29","author":"Yuen","year":"2010","journal-title":"Matrix Biol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1161\/HYPERTENSIONAHA.125.25408","article-title":"Cellular Senescence Mediates Doxorubicin Chemotherapy-Induced Aortic Stiffening: Role of Glycation Stress","volume":"82","author":"Venkatasubramanian","year":"2025","journal-title":"Hypertension"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.molmed.2012.03.005","article-title":"Protein misfolding and aggregation in cataract disease and prospects for prevention","volume":"18","author":"Moreau","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1007\/s00125-011-2393-0","article-title":"Protection against methylglyoxal-derived AGEs by regulation of glyoxalase 1 prevents retinal neuroglial and vasodegenerative pathology","volume":"55","author":"Berner","year":"2012","journal-title":"Diabetologia"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1093\/nar\/gkab014","article-title":"The metabolite methylglyoxal-mediated gene expression is associated with histone methylglyoxalation","volume":"49","author":"Fu","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"101038","DOI":"10.1016\/j.arr.2020.101038","article-title":"Calorie restriction for enhanced longevity: The role of novel dietary strategies in the present obesogenic environment","volume":"64","author":"Dorling","year":"2020","journal-title":"Ageing Res. Rev."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1016\/j.cmet.2019.01.018","article-title":"Caloric Restriction Mimetics against Age-Associated Disease: Targets, Mechanisms, and Therapeutic Potential","volume":"29","author":"Madeo","year":"2019","journal-title":"Cell Metab."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Alaseem, A.M., Aldali, J.A., Alasiri, G., Alhujaily, M., AlHussaini, K.I., and AlKhamees, O.A. (2025). Glyoxalase 1 gene expression in various types of cancer cells immunopathology: A pan-cancer analysis study. Front. Oncol., 15.","DOI":"10.3389\/fonc.2025.1610886"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1159\/000367800","article-title":"Glyoxalase I in tumor cell proliferation and survival and as a potential target for anticancer therapy","volume":"37","author":"Geng","year":"2014","journal-title":"Oncol. Res. Treat."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Zhou, D., Duan, Z., Li, Z., Ge, F., Wei, R., and Kong, L. (2022). The significance of glycolysis in tumor progression and its relationship with the tumor microenvironment. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1091779"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"102455","DOI":"10.1016\/j.genrep.2026.102455","article-title":"Methylglyoxal: Hijack-to-survive paradigm of cancer progression","volume":"43","author":"Patel","year":"2026","journal-title":"Gene Rep."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"547","DOI":"10.3892\/ol.2021.12808","article-title":"Glyoxalase 1 and protein kinase C\u03bb as potential therapeutic targets for late-stage breast cancer","volume":"22","author":"Motomura","year":"2021","journal-title":"Oncol. Lett."},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Ozanic, K., Watanabe, A.S.A., Machado, A.B.F., da Silva, V.L., Dias, V.C., and Diniz, C.G. (2025). Long COVID: General Perceptions and Challenges in Diagnosis and Management. COVID, 5.","DOI":"10.20944\/preprints202501.0164.v1"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Georgieva, E., Ananiev, J., Yovchev, Y., Arabadzhiev, G., Abrashev, H., Abrasheva, D., Atanasov, V., Kostandieva, R., Mitev, M., and Petkova-Parlapanska, K. (2023). COVID-19 Complications: Oxidative Stress, Inflammation, and Mitochondrial and Endothelial Dysfunction. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914876"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Stojanovic, M., Djuric, M., Nenadic, I., Bojic, S., Andrijevic, A., Popovic, A., and Pesic, S. (2025). Vascular Complications of Long COVID\u2014From Endothelial Dysfunction to Systemic Thrombosis: A Systematic Review. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27010433"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"729","DOI":"10.2147\/VHRM.S519426","article-title":"Vascular Endothelium in Health and Disease: Structure, Function, Assessment and Role in Metabolic Disorders","volume":"21","author":"Pluta","year":"2025","journal-title":"Vasc. Health Risk Manag."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Nigro, C., Leone, A., Raciti, G.A., Longo, M., Mirra, P., Formisano, P., Beguinot, F., and Miele, C. (2017). Methylglyoxal-Glyoxalase 1 Balance: The Root of Vascular Damage. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18010188"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"37737","DOI":"10.1038\/srep37737","article-title":"Glyoxalase 1-knockdown in human aortic endothelial cells\u2014Effect on the proteome and endothelial function estimates","volume":"6","author":"Stratmann","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Popa, E., Popa, A.E., Poroch, M., Poroch, V., Ungureanu, M.I., Slanina, A.M., Bacusca, A., and Coman, E.A. (2025). The Molecular Mechanisms of Cognitive Dysfunction in Long COVID: A Narrative Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115102"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Farida, N., Levin, L., Kuhn, T., and Vivian, J. (2025). Understanding the Association Between Long COVID, Neurological Symptoms, and Anxiety. COVID, 5.","DOI":"10.3390\/covid5100177"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.freeradbiomed.2023.11.012","article-title":"Methylglyoxal accumulation contributes to accelerated brain aging in spontaneously hypertensive rats","volume":"210","author":"Zhang","year":"2024","journal-title":"Free Radic. Biol. Med."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1186\/s10020-024-00905-9","article-title":"Advanced glycation end products and reactive oxygen species: Uncovering the potential role of ferroptosis in diabetic complications","volume":"30","author":"Chen","year":"2024","journal-title":"Mol. Med."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/5\/822\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T05:51:25Z","timestamp":1779688285000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/16\/5\/822"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,15]]},"references-count":110,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["life16050822"],"URL":"https:\/\/doi.org\/10.3390\/life16050822","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,15]]}}}