{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T21:53:52Z","timestamp":1768773232635,"version":"3.49.0"},"reference-count":45,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hyperglycemia is a potent risk factor for the development and progression of diabetes-induced nephropathy. Dendropanoxide (DPx) is a natural compound isolated from Dendropanax morbifera (Araliaceae) that exerts various biological effects. However, the role of DPx in hyperglycemia-induced renal tubular cell injury remains unclear. The present study explored the protective mechanism of DPx on high glucose (HG)-induced cytotoxicity in kidney tubular epithelial NRK-52E cells. The cells were cultured with normal glucose (5.6\u2009mM), HG (30\u2009mM), HG + metformin (10\u2009\u00b5M), or HG + DPx (10\u2009\u00b5M) for 48\u2009h, and cell cycle and apoptosis were analyzed. Malondialdehyde (MDA), advanced glycation end products (AGEs), and reactive oxygen species (ROS) were measured. Protein-based nephrotoxicity biomarkers were measured in both the culture media and cell lysates. MDA and AGEs were significantly increased in NRK-52E cells cultured with HG, and these levels were markedly reduced by pretreatment\n          with DPx or metformin. DPx significantly reduced the levels of kidney injury molecule-1 (KIM-1), pyruvate kinase M2 (PKM2), selenium-binding protein 1 (SBP1), or neutrophil gelatinase-associated lipocalin (NGAL) in NRK-52E cells cultured under HG conditions. Furthermore, treatment with DPx significantly increased antioxidant enzyme activity. DPx protects against HG-induced renal tubular cell damage, which may be mediated by its ability to inhibit oxidative stress through the protein kinase B\/mammalian target of the rapamycin (AKT\/mTOR) signaling pathway. These findings suggest that DPx can be used as a new drug for the treatment of high glucose-induced diabetic nephropathy.<\/jats:p>","DOI":"10.1055\/a-2220-9301","type":"journal-article","created":{"date-parts":[[2023,12,2]],"date-time":"2023-12-02T00:14:15Z","timestamp":1701476055000},"page":"256-266","source":"Crossref","is-referenced-by-count":3,"title":["Dendropanoxide Attenuates High Glucose-induced Oxidative Damage in NRK-52E Cells via AKT\/mTOR Signaling Pathway"],"prefix":"10.1055","volume":"90","author":[{"given":"Song Hee","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Seobu-ro 2066, Kyunggi-Do, Suwon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ju Ri","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Seobu-ro 2066, Kyunggi-Do, Suwon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joo Kyung","family":"Shin","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Seobu-ro 2066, Kyunggi-Do, Suwon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin-Sol","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Seobu-ro 2066, Kyunggi-Do, Suwon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young Mi","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Duksung Women\u02bcs University, Seoul, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8327-3703","authenticated-orcid":false,"given":"Jeong Hwan","family":"Kwak","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Seobu-ro 2066, Kyunggi-Do, Suwon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyung Sik","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Sungkyunkwan University, Seobu-ro 2066, Kyunggi-Do, Suwon, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2024,1,16]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"14790","DOI":"10.1038\/s41598-020-71908-9","article-title":"Global, regional, and national burden and trend of diabetes in 195 countries and territories: an analysis from 1990 to 2025","volume":"10","author":"X Lin","year":"2020","journal-title":"Sci Rep"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.2215\/CJN.11491116","article-title":"Diabetic kidney disease: Challenges, progress, and possibilities","volume":"12","author":"R Z Alicic","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mcna.2012.10.001","article-title":"Epidemiology of diabetic kidney disease","volume":"97","author":"A T Reutens","year":"2013","journal-title":"Med Clin North Am"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1136\/jcp.2005.035592","article-title":"Distinguishing diabetic nephropathy from other causes of glomerulosclerosis: An update","volume":"60","author":"K O Alsaad","year":"2007","journal-title":"J Clin Pathol"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1161\/CIRCRESAHA.110.223545","article-title":"Oxidative stress and diabetic complications","volume":"107","author":"F Giacco","year":"2010","journal-title":"Circ Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"5695","DOI":"10.2174\/1381612811319320005","article-title":"Hyperglycemia-induced oxidative stress and its role in diabetes mellitus related cardiovascular diseases","volume":"19","author":"T Fiorentino","year":"2013","journal-title":"Curr Pharma Des"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ijdm.2010.09.002","article-title":"Endothelial cell dysfunction in hyperglycemia: Phenotypic change, intracellular signaling modification, ultrastructural alteration, and potential clinical outcomes","volume":"2","author":"D Popov","year":"2010","journal-title":"Int J Diabetes Mellitus"},{"key":"ref8","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":"M Brownlee","year":"2005","journal-title":"Diabetes"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.2337\/db08-0057","article-title":"Oxidative stress as a major culprit in kidney disease in diabetes","volume":"57","author":"J M Forbes","year":"2008","journal-title":"Diabetes"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1089\/ars.2016.6665","article-title":"Oxidant mechanisms in renal injury and disease","volume":"25","author":"B B Ratliff","year":"2016","journal-title":"Antioxid Redox Signal"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.redox.2016.09.007","article-title":"Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy","volume":"10","author":"A Czajka","year":"2016","journal-title":"Redox Biol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"15026","DOI":"10.3390\/ijms150915026","article-title":"The protective effect of glycyrrhizic acid on renal tubular epithelial cell injury induced by high glucose","volume":"15","author":"S Hou","year":"2014","journal-title":"Int J Mol Sci"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/ndt\/gfv264","article-title":"New developments concerning the proximal tubule in diabetic nephropathy: In vitro models and mechanisms","volume":"30","author":"J Slyne","year":"2015","journal-title":"Nephrol Dial Transplant"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1146\/annurev-physiol-020911-153333","article-title":"Renal function in diabetic disease models: The tubular system in the pathophysiology of the diabetic kidney","volume":"74","author":"V Vallon","year":"2012","journal-title":"Annu Rev Physiol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1042\/CS20120198","article-title":"Inflammation and the pathogenesis of diabetic nephropathy","volume":"124","author":"J Wada","year":"2013","journal-title":"Clin Sci"},{"key":"ref16","first-page":"835","article-title":"ROS induces epithelial-mesenchymal transition via the TGF-\u03b21\/PI3K\/AKT\/mTOR pathway in diabetic nephropathy","volume":"17","author":"Q Lu","year":"2019","journal-title":"Exp Ther Med"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"315494","DOI":"10.1155\/2014\/315494","article-title":"Role of nutrient-sensing signals in the pathogenesis of diabetic nephropathy","volume":"2014","author":"S Kume","year":"2014","journal-title":"Biomed Res Int"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.1681\/ASN.2008111186","article-title":"The role of the mammalian target of rapamycin (mTOR) in renal disease","volume":"20","author":"W Lieberthal","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1248\/bpb.b15-00823","article-title":"Potent anti-inflammatory and analgesic actions of the chloroform extract of dendropanax morbifera mediated by the Nrf2\/HO-1 pathway","volume":"39","author":"M Akram","year":"2016","journal-title":"Biol Pharm Bull"},{"key":"ref20","first-page":"3732317","article-title":"Antihyperuricemic effect of Dendropanax morbifera leaf extract in rodent models","volume":"2021","author":"D Lee","year":"2021","journal-title":"Evid Based Complement Alternat Med"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"146","DOI":"10.6118\/jmm.2017.23.3.146","article-title":"The clinical effects of Dendropanax Morbifera on postmenopausal symptoms: Review article","volume":"23","author":"M Kim","year":"2017","journal-title":"J Menopausal Med"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"84","DOI":"10.3390\/antiox9010084","article-title":"Dendropanax morbifera protects against renal fibrosis in streptozotocin-induced diabetic rats","volume":"9","author":"R Sachan","year":"2020","journal-title":"Antioxidants"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1177\/0960327110382131","article-title":"Antidiabetic effects of dendropanoxide from leaves of Dendropanax morbifera Leveille in normal and streptozotocin-induced diabetic rats","volume":"30","author":"H I Moon","year":"2011","journal-title":"Human Exp Toxicol"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/antiox9010084","article-title":"Dendropanax morbifera protects against renal fibrosis in streptozotocin-induced diabetic rats","volume":"9","author":"R Sachan","year":"2020","journal-title":"Antioxidants"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"111605","DOI":"10.1016\/j.fct.2020.111605","article-title":"Protective effects of dendropanoxide isolated from Dendropanax morbifera against cisplatin-induced acute kidney injury via the AMPK\/mTOR signaling pathway","volume":"145","author":"Y J Park","year":"2020","journal-title":"Food Chem Toxicol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"962","DOI":"10.2174\/138161208784139729","article-title":"Role of advanced glycation end products (AGEs) and oxidative stress in diabetic retinopathy","volume":"14","author":"S Yamagishi","year":"2008","journal-title":"Curr Pharm Des"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1007\/s00467-018-4005-4","article-title":"Oxidative stress in chronic kidney disease","volume":"34","author":"K Daenen","year":"2019","journal-title":"Pediatric Nephrol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1002\/jcb.23088","article-title":"High glucose concentration affects the oxidant-antioxidant balance in cultured mouse podocytes","volume":"112","author":"A Piwkowska","year":"2011","journal-title":"J Cell Biochem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e12763","DOI":"10.1111\/cpr.12763","article-title":"Crosstalk between tubular epithelial cells and glomerular endothelial cells in diabetic kidney disease","volume":"53","author":"S J Chen","year":"2020","journal-title":"Cell Prolif"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40364-015-0042-3","article-title":"Urinary biomarkers for early diabetic nephropathy in type 2 diabetic patients","volume":"3","author":"T Fiseha","year":"2015","journal-title":"Biomark Res"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1080\/15287394.2017.1299655","article-title":"Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury","volume":"80","author":"K S Kim","year":"2017","journal-title":"J Toxicol Environ Health A"},{"key":"ref32","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":"H Ha","year":"2008","journal-title":"Diabetes Res Clin Pract"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/s00418-004-0678-9","article-title":"Hyperglycemia-induced oxidative stress in diabetic complications","volume":"122","author":"G L King","year":"2004","journal-title":"Histochem Cell Biol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1096\/fj.02-0130fje","article-title":"High glucose-induced oxidative stress causes apoptosis in proximal tubular epithelial cells and is mediated by multiple caspases","volume":"17","author":"D A Allen","year":"2003","journal-title":"FASEB J"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/jbt.10058","article-title":"Diabetes, oxidative stress, and antioxidants: A review","volume":"17","author":"A C Maritim","year":"2003","journal-title":"J Bioch Mol Toxicol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1016\/j.biopha.2016.11.133","article-title":"Modulation of the lipid profile and insulin levels of streptozotocin induced diabetic rats by ethanol extract of Cnidoscolus aconitifolius leaves and some fractions: Effect on the oral glucose tolerance of normoglycemic rats","volume":"86","author":"N K Achi","year":"2017","journal-title":"Biomed Pharmacother"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"542","DOI":"10.3390\/biom12040542","article-title":"Advanced glycation end products and diabetes mellitus: Mechanisms and perspectives","volume":"12","author":"M Khalid","year":"2022","journal-title":"Biomolecules"},{"key":"ref38","first-page":"6052","article-title":"Curcumin suppresses AGEs induced apoptosis in tubular epithelial cells via protective autophagy","volume":"14","author":"Y Wei","year":"2017","journal-title":"Exp Ther Med"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"948417","DOI":"10.1155\/2015\/948417","article-title":"Inflammatory cytokines in diabetic nephropathy","volume":"2015","author":"J Donate-Correa","year":"2015","journal-title":"J Diabetes Res"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/nrneph.2014.114","article-title":"Inflammatory processes in renal fibrosis","volume":"10","author":"X M Meng","year":"2014","journal-title":"Nat Rev Nephrol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1172\/JCI200319270","article-title":"Targeted disruption of TGF-\u03b21\/Smad3 signaling protects against renal tubulointerstitial fibrosis induced by unilateral ureteral obstruction","volume":"112","author":"M Sato","year":"2003","journal-title":"J Clin Invest"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/sj.cr.7290105","article-title":"MAPK signal pathways in the regulation of cell proliferation in mammalian cells","volume":"12","author":"Z Wei","year":"2002","journal-title":"Cell Res"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1016\/S0006-291X(02)00557-0","article-title":"Acute and chronic treatment of ob\/ob and db\/db mice with AICAR decreases blood glucose concentrations","volume":"294","author":"A E Halseth","year":"2002","journal-title":"Biochem Biophy Res Commun"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1111\/j.1463-1326.2011.01466.x","article-title":"Metformin opposes impaired AMPK and SIRT1 function and deleterious changes in core clock protein expression in white adipose tissue of genetically-obese db\/db mice","volume":"13","author":"P W Caton","year":"2011","journal-title":"Diabetes Obes Metab"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1055\/s-2002-32073","article-title":"Interference of plant extracts, phytoestrogens and antioxidants with the MTT tetrazolium assay","volume":"68","author":"R Bruggisser","year":"2002","journal-title":"Planta Med"}],"container-title":["Planta Medica"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2220-9301.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T14:52:02Z","timestamp":1730818322000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2220-9301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,1]]},"references-count":45,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2024,3,18]]},"published-print":{"date-parts":[[2024,4]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2220-9301","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0032-0943","1439-0221"],"issn-type":[{"value":"0032-0943","type":"print"},{"value":"1439-0221","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,12,1]]},"published":{"date-parts":[[2023,12,1]]}}}