{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:57:36Z","timestamp":1787029056348,"version":"build-2736575974"},"reference-count":82,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Increased blood glucose in diabetic individuals results in the formation of advanced glycation end products (AGEs), causing various adverse effects on kidney cells, thereby leading to diabetic nephropathy (DN). In this study, the antiglycative potential of Swertiamarin (SM) isolated from the methanolic extract of E. littorale was explored. The effect of SM on protein glycation was studied by incubating bovine serum albumin with fructose at 60 \u00b0C in the presence and absence of different concentrations of swertiamarin for 24 h. For comparative analysis, metformin was also used at similar concentrations as SM. Further, to understand the role of SM in preventing DN, in vitro studies using NRK-52E cells were done by treating cells with methylglyoxal (MG) in the presence and absence of SM. SM showed better antiglycative potential as compared to metformin. In addition, SM could prevent the MG mediated pathogenesis in DN by reducing levels of argpyrimidine, oxidative stress and epithelial mesenchymal transition in kidney cells. SM also downregulated the expression of interleukin-6, tumor necrosis factor-\u03b1 and interleukin-1\u03b2. This study, for the first time, reports the antiglycative potential of SM and also provides novel insights into the molecular mechanisms by which SM prevents toxicity of MG on rat kidney cells.<\/jats:p>","DOI":"10.3390\/molecules26092748","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T10:06:12Z","timestamp":1620381972000},"page":"2748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Protective Effects of Swertiamarin against Methylglyoxal-Induced Epithelial-Mesenchymal Transition by Improving Oxidative Stress in Rat Kidney Epithelial (NRK-52E) Cells"],"prefix":"10.3390","volume":"26","author":[{"given":"Kirti","family":"Parwani","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, P. D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa 388421, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farhin","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, P. D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa 388421, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2817-6986","authenticated-orcid":false,"given":"Dhara","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, P. D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa 388421, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6612-3773","authenticated-orcid":false,"given":"Palash","family":"Mandal","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, P. D. Patel Institute of Applied Sciences, Charotar University of Science and Technology, Changa 388421, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2003). Writing Team for the Diabetes Control and Complications Trial\/Epidemiology of Diabetes Interventions and Complications Research Group Sustained Effect of Intensive Treatment of Type 1 Diabetes Mellitus on Development and Progression of Diabetic Nephropathy. JAMA, 290, 2159\u20132167.","DOI":"10.1001\/jama.290.16.2159"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1056\/NEJM199807093390202","article-title":"Reversal of Lesions of Diabetic Nephropathy after Pancreas Transplantation","volume":"339","author":"Fioretto","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1001\/jama.1994.03520080042041","article-title":"Effect of glycemic control on early diabetic renal lesions. A 5-year randomized controlled clinical trial of insulin-dependent diabetic kidney transplant recipients","volume":"272","author":"Barbosa","year":"1994","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"249","DOI":"10.2337\/db09-0801","article-title":"Hyperglycemia-Induced Reactive Oxygen Species Increase Expression of the Receptor for Advanced Glycation End Products (RAGE) and RAGE Ligands","volume":"59","author":"Yao","year":"2009","journal-title":"Diabetes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"14279","DOI":"10.1016\/S0021-9258(17)43857-9","article-title":"13C NMR investigation of nonenzymatic glucosylation of protein. Model studies using RNase A","volume":"258","author":"Neglia","year":"1983","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.clinbiochem.2004.09.007","article-title":"Importance of measuring products of non-enzymatic glycation of proteins","volume":"38","author":"Lapolla","year":"2005","journal-title":"Clin. Biochem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1053\/meta.2003.50035","article-title":"Increased serum levels of the specific AGE-compound methylglyoxal-derived hydroimidazolone in patients with type 2 diabetes","volume":"52","author":"Kilhovd","year":"2003","journal-title":"Metabolism"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1007\/s001250100000","article-title":"Interaction of metabolic and haemodynamic factors in mediating experimental diabetic nephropathy","volume":"44","author":"Cooper","year":"2001","journal-title":"Diabetologia"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1515\/bmc-2016-0021","article-title":"Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy","volume":"7","author":"Pasupulati","year":"2016","journal-title":"Biomol. Concepts"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"194","DOI":"10.2337\/diacare.20.2.194","article-title":"Total Radical-Trapping Antioxidant Parameter in NIDDM Patients","volume":"20","author":"Ceriello","year":"1997","journal-title":"Diabetes Care"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/S1016-8478(23)13727-7","article-title":"Modification and inactivation of human Cu,Zn-superoxide dismutase by methylglyoxal","volume":"15","author":"Kang","year":"2003","journal-title":"Mol. Cells"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.abb.2017.06.018","article-title":"Destructive effect of non-enzymatic glycation on catalase and remediation via curcumin","volume":"630","author":"Najjar","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1248\/cpb.58.980","article-title":"Characterization and Antiglycation Activity of Phenolic Constituents from Viscum album (European Mistletoe)","volume":"58","author":"Choudhary","year":"2010","journal-title":"Chem. Pharm. Bull."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.carbpol.2010.11.016","article-title":"Attenuating effects of Ganoderma lucidum polysaccharides on myocardial collagen cross-linking relates to advanced glycation end product and antioxidant enzymes in high-fat-diet and streptozotocin-induced diabetic rats","volume":"84","author":"Meng","year":"2011","journal-title":"Carbohydr. Polym."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.foodchem.2009.10.018","article-title":"Inhibitory effects of microalgal extracts on the formation of advanced glycation endproducts (AGEs)","volume":"120","author":"Sun","year":"2010","journal-title":"Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jep.2007.01.030","article-title":"Experimental diabetes treated with Achillea santolina: Effect on pancreatic oxidative parameters","volume":"112","author":"Yazdanparast","year":"2007","journal-title":"J. Ethnopharmacol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0378-8741(02)00077-6","article-title":"Effect of chronic treatment with Enicostemma littorale in non-insulin-dependent diabetic (NIDDM) rats","volume":"81","author":"Murali","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/0378-8741(91)90157-9","article-title":"Anticholinergic action of Swertia japonica and an active constituent","volume":"33","author":"Yamahara","year":"1991","journal-title":"J. Ethnopharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s11418-009-0350-8","article-title":"Antihyperlipidaemic activity of swertiamarin, a secoiridoid glycoside in poloxamer-407-induced hyperlipidaemic rats","volume":"63","author":"Vaidya","year":"2009","journal-title":"J. Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1002\/ptr.3708","article-title":"Beneficial Effects of Swertiamarin on Dyslipidaemia in Streptozotocin-induced Type 2 Diabetic Rats","volume":"26","author":"Vaidya","year":"2012","journal-title":"Phytotherapy Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jep.2010.04.019","article-title":"Antioxidant and hepatoprotective effect of swertiamarin from Enicostemma axillare against d-galactosamine induced acute liver damage in rats","volume":"130","author":"Jaishree","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"110561","DOI":"10.1016\/j.biopha.2020.110561","article-title":"Swertiamarin and quercetin combination ameliorates hyperglycemia, hyperlipidemia and oxidative stress in streptozotocin-induced type 2 diabetes mellitus in wistar rats","volume":"130","author":"Jaishree","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2418","DOI":"10.1021\/jf011339n","article-title":"Protective Activity of Green Tea against Free Radical- and Glucose-Mediated Protein Damage","volume":"50","author":"Nakagawa","year":"2002","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1080\/13880200490885095","article-title":"A Rapid Method for the Isolation of Swertiamarin from Enicostemma littorale","volume":"42","author":"Vishwakarma","year":"2004","journal-title":"Pharm. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S0305-1978(02)00200-4","article-title":"Swertiamarin from Enicostemma axillare subsp. axillare (Gentianaceae)","volume":"31","author":"Magora","year":"2003","journal-title":"Biochem. Syst. Ecol."},{"key":"ref_26","first-page":"2","article-title":"Separation and Identification of Swertiamarin from Enicostema axillare Lam. Raynal by Centrifugal Partition Chromatography and Nuclear Magnetic Resonance-Mass Spectrometry","volume":"1","author":"Rana","year":"2014","journal-title":"J. Pharm Sci. Emerg. Drugs"},{"key":"ref_27","first-page":"1","article-title":"Improved and Rapid HPLC-PDA Method for Identification and Quantification of Swertiamarin in the Aerial Parts of Enicostemma Axillare","volume":"10","author":"Rana","year":"2012","journal-title":"Malaysian J. Pharma Sci."},{"key":"ref_28","first-page":"01","article-title":"An Effective Method for Isolation of Pure Swertiamarin from Enicostemma littorale Blume","volume":"8","author":"Kumar","year":"2018","journal-title":"Indo Glob. J. Pharm. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2242","DOI":"10.1159\/000475639","article-title":"Antioxidant and Hepatoprotective Effect of Swertiamarin on Carbon Tetrachloride-Induced Hepatotoxicity via the Nrf2\/HO-1 Pathway","volume":"41","author":"Wu","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/3164734","article-title":"The Role of the Reactive Oxygen Species and Oxidative Stress in the Pathomechanism of the Age-Related Ocular Diseases and Other Pathologies of the Anterior and Posterior Eye Segments in Adults","volume":"2016","author":"Nita","year":"2016","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"946","DOI":"10.2174\/138161208784139710","article-title":"Role of AGEs in Diabetic Nephropathy","volume":"14","author":"Fukami","year":"2008","journal-title":"Curr. Pharm. Des."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.diabres.2004.09.004","article-title":"Advanced glycation endproducts\u2014role in pathology of diabetic complications","volume":"67","author":"Ahmed","year":"2005","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.4196\/kjpp.2014.18.1.1","article-title":"Advanced Glycation End Products and Diabetic Complications","volume":"18","author":"Singh","year":"2014","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.fitote.2005.03.021","article-title":"Ilex paraguariensis extracts inhibit AGE formation more efficiently than green tea","volume":"76","author":"Lunceford","year":"2005","journal-title":"Fitoter."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1515\/CCLM.2003.180","article-title":"Glyoxal and Methylglyoxal Levels in Diabetic Patients: Quantitative Determination by a New GC\/MS Method","volume":"41","author":"Lapolla","year":"2003","journal-title":"Clin. Chem. Lab. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1681\/ASN.2014101047","article-title":"Uremic Toxicity of Advanced Glycation End Products in CKD","volume":"27","author":"Stinghen","year":"2015","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"28676","DOI":"10.1074\/jbc.M114.563593","article-title":"Extending the Spectrum of \u03b1-Dicarbonyl Compounds In Vivo","volume":"289","author":"Henning","year":"2014","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2666","DOI":"10.1016\/j.foodres.2011.05.022","article-title":"Phytochemicals from berries and grapes inhibited the formation of advanced glycation end-products by scavenging reactive carbonyls","volume":"44","author":"Wang","year":"2011","journal-title":"Food Res. Int."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-55779-3","article-title":"B procyanidins of Annona crassiflora fruit peel inhibited glycation, lipid peroxidation and protein-bound carbonyls, with protective effects on glycated catalase","volume":"9","author":"Justino","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/j.ijbiomac.2007.07.014","article-title":"Cyperus rotundus suppresses AGE formation and protein oxidation in a model of fructose-mediated protein glycoxidation","volume":"41","author":"Ardestani","year":"2007","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Ahmad, S., Shahab, U., Baig, M.H., Khan, M.S., Khan, M.S., Srivastava, A.K., and Saeed, M. (2013). Moinuddin Inhibitory Effect of Metformin and Pyridoxamine in the Formation of Early, Intermediate and Advanced Glycation End-Products. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0072128"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1055\/s-0032-1321878","article-title":"Metformin Inhibits Advanced Glycation End Products (AGEs)-induced Renal Tubular Cell Injury by Suppressing Reactive Oxygen Species Generation via Reducing Receptor for AGEs (RAGE) Expression","volume":"44","author":"Ishibashi","year":"2012","journal-title":"Horm. Metab. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6439","DOI":"10.3390\/molecules18066439","article-title":"Isoferulic Acid, a New Anti-Glycation Agent, Inhibits Fructose- and Glucose-Mediated Protein Glycation In Vitro","volume":"18","author":"Meeprom","year":"2013","journal-title":"Molecules"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.cca.2006.10.020","article-title":"Immunoglobulin glycation with fructose: A comparative study","volume":"378","author":"Jairajpuri","year":"2007","journal-title":"Clin. Chim. Acta"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1002\/iub.1375","article-title":"Fructosylation generates neo-epitopes on human serum albumin","volume":"67","author":"Allarakha","year":"2015","journal-title":"IUBMB Life"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1002\/jsfa.8701","article-title":"Differentiation of glycated residue numbers on heat-induced structural changes of bovine serum albumin","volume":"98","author":"Liu","year":"2018","journal-title":"J. Sci. Food Agric."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1042\/bj3280599","article-title":"Glycation-induced inactivation and loss of antigenicity of catalase and superoxide dismutase","volume":"328","author":"Yan","year":"1997","journal-title":"Biochem. J."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"S42","DOI":"10.1016\/j.diabres.2008.09.017","article-title":"Role of reactive oxygen species in the pathogenesis of diabetic nephropathy","volume":"82","author":"Ha","year":"2008","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1046\/j.1523-1755.2003.00829.x","article-title":"Methylglyoxal induces apoptosis through activation of p38 mitogen-activated protein kinase in rat mesangial cells","volume":"63","author":"Liu","year":"2003","journal-title":"Kidney Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"18492","DOI":"10.1074\/jbc.274.26.18492","article-title":"Methylglyoxal Modification of Protein","volume":"274","author":"Oya","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1006\/abio.2001.4992","article-title":"Chromatographic Quantification of Argpyrimidine, a Methylglyoxal-Derived Product in Tissue Proteins: Comparison with Pentosidine","volume":"290","author":"Wilker","year":"2001","journal-title":"Anal. Biochem."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0014-5793(03)00874-3","article-title":"Methylglyoxal modifies heat shock protein 27 in glomerular mesangial cells","volume":"551","author":"Padival","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/biof.5520340208","article-title":"Lipid peroxidation products as oxidative stress biomarkers","volume":"34","author":"Niki","year":"2008","journal-title":"BioFactors"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/360438","article-title":"Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s13105-016-0531-3","article-title":"Ferulic acid prevents methylglyoxal-induced protein glycation, DNA damage, and apoptosis in pancreatic \u03b2-cells","volume":"73","author":"Sompong","year":"2016","journal-title":"J. Physiol. Biochem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2043","DOI":"10.2337\/db09-1766","article-title":"Deletion of the Receptor for Advanced Glycation End Products Reduces Glomerulosclerosis and Preserves Renal Function in the Diabetic OVE26 Mouse","volume":"59","author":"Reiniger","year":"2010","journal-title":"Diabetes"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1111\/j.1365-2362.2009.02203.x","article-title":"Intensive insulin therapy decreases urinary MCP-1 and ICAM-1 excretions in incipient diabetic nephropathy","volume":"39","author":"Ye","year":"2009","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4161\/oxim.3.2.11148","article-title":"Advanced Glycation end Products, Oxidative Stress and Diabetic Nephropathy","volume":"3","author":"Yamagishi","year":"2010","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.kint.2015.12.025","article-title":"Epithelial-to-mesenchymal transition of tubular epithelial cells in renal fibrosis: A new twist on an old tale","volume":"89","author":"Menon","year":"2016","journal-title":"Kidney Int."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.3892\/mmr.2015.3556","article-title":"Curcumin protects renal tubular epithelial cells from high glucose-induced epithelial-to-mesenchymal transition through Nrf2-mediated upregulation of heme oxygenase-1","volume":"12","author":"Zhang","year":"2012","journal-title":"Mol. Med. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1681\/ASN.2006050525","article-title":"Connective Tissue Growth Factor Plays an Important Role in Advanced Glycation End Product\u2013Induced Tubular Epithelial-to-Mesenchymal Transition: Implications for Diabetic Renal Disease","volume":"17","author":"Burns","year":"2006","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Lv, Z.-M., Wang, Q., Wan, Q., Lin, J.-G., Hu, M.-S., Liu, Y.-X., and Wang, R. (2011). The Role of the p38 MAPK Signaling Pathway in High Glucose-Induced Epithelial-Mesenchymal Transition of Cultured Human Renal Tubular Epithelial Cells. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0022806"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"F1263","DOI":"10.1152\/ajprenal.00475.2009","article-title":"Troglitazone ameliorates high glucose-induced EMT and dysfunction of SGLTs through PI3K\/Akt, GSK-3\u03b2, Snail1, and \u03b2-catenin in renal proximal tubule cells","volume":"298","author":"Lee","year":"2010","journal-title":"Am. J. Physiol. Physiol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.jdiacomp.2012.06.014","article-title":"20-Hydroxyecdysone attenuates TGF-\u03b21-induced renal cellular fibrosis in proximal tubule cells","volume":"26","author":"Hung","year":"2012","journal-title":"J. Diabetes Complicat."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Parwani, K., and Mandal, P. (2020). Role of advanced glycation end products and insulin resistance in diabetic nephropathy. Arch. Physiol. Biochem., 1\u201313.","DOI":"10.1080\/13813455.2020.1797106"},{"key":"ref_66","first-page":"835","article-title":"ROS induces epithelial-mesenchymal transition via the TGF-\u03b21\/PI3K\/Akt\/mTOR pathway in diabetic nephropathy","volume":"17","author":"Lu","year":"2018","journal-title":"Exp. Ther. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"850","DOI":"10.2337\/db09-1342","article-title":"The Protective Role of Nrf2 in Streptozotocin-Induced Diabetic Nephropathy","volume":"59","author":"Jiang","year":"2010","journal-title":"Diabetes"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1681\/ASN.2007101099","article-title":"Heme Oxygenase-1 Deficiency Promotes Epithelial-Mesenchymal Transition and Renal Fibrosis","volume":"19","author":"Kie","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"90","DOI":"10.5455\/aim.2015.23.90-96","article-title":"Selective Inhibition on RAGE-binding AGEs Required by Bioactive Peptide Alpha-S2 Case in Protein from Goat Ethawah Breed Milk: Study of Biological Modeling","volume":"23","author":"Fatchiyah","year":"2015","journal-title":"Acta Inform. Medica"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1080\/14786419.2015.1071366","article-title":"RP-HPLC analysis of seco-iridoid glycoside swertiamarin from differentSwertiaspecies","volume":"30","author":"Kshirsagar","year":"2016","journal-title":"Nat. Prod. Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1021\/bi00406a016","article-title":"Role of fructose in glycation and cross-linking of proteins","volume":"27","author":"McPherson","year":"1988","journal-title":"Biochemistry"},{"key":"ref_72","unstructured":"Riss, T.L., Moravec, R.A., Niles, A.L., Duellman, S., Benink, H.A., Worzella, T.J., and Minor, L. (2004). Assay Guidance Manual, Eli Lilly & Company and the National Center for Advancing Translational Sciences."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/S0891-5849(98)00209-3","article-title":"Free radical\u2013induced megamitochondria formation and apoptosis","volume":"26","author":"Karbowski","year":"1999","journal-title":"Free. Radic. Biol. Med."},{"key":"ref_74","first-page":"88","article-title":"Measurement of total malondialdehyde in plasma and tissues by high-performance liquid chromatography and thiobarbituric acid assay","volume":"11","author":"Tukozkan","year":"2006","journal-title":"Firat Tip Dergisi."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1078","DOI":"10.1111\/acer.13398","article-title":"Protective Effects of Diallyl Sulfide Against Ethanol-Induced Injury in Rat Adipose Tissue and Primary Human Adipocytes","volume":"41","author":"Kema","year":"2017","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1161\/CIRCRESAHA.109.195834","article-title":"S100B Interaction with the Receptor for Advanced Glycation End Products (RAGE)","volume":"106","author":"Tsoporis","year":"2010","journal-title":"Circ. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1093\/nar\/gkh131","article-title":"UniProt: The Universal Protein knowledgebase","volume":"32","author":"Apweiler","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1611","DOI":"10.1021\/cb4001553","article-title":"Stable RAGE-Heparan Sulfate Complexes Are Essential for Signal Transduction","volume":"8","author":"Xu","year":"2013","journal-title":"ACS Chem. Biol."},{"key":"ref_79","unstructured":"(2021). Schr\u00f6dinger Release, Version 12.7.156, Maestro Schr\u00f6dinger LLC."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s10822-013-9644-8","article-title":"Protein and ligand preparation: Parameters, protocols, and influence on virtual screening enrichments","volume":"27","author":"Sastry","year":"2013","journal-title":"J. Comput. Mol. Des."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s10822-010-9349-1","article-title":"Towards the comprehensive, rapid, and accurate prediction of the favorable tautomeric states of drug-like molecules in aqueous solution","volume":"24","author":"Greenwood","year":"2010","journal-title":"J. Comput. Mol. Des."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/prot.10613","article-title":"A hierarchical approach to all-atom protein loop prediction","volume":"55","author":"Jacobson","year":"2004","journal-title":"Proteins: Struct. Funct. Bioinform."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/9\/2748\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:57:58Z","timestamp":1760162278000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/26\/9\/2748"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,7]]},"references-count":82,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2021,5]]}},"alternative-id":["molecules26092748"],"URL":"https:\/\/doi.org\/10.3390\/molecules26092748","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,7]]}}}