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Quality Improvement Plan Project","award":["2023szyzk71"],"award-info":[{"award-number":["2023szyzk71"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Previous studies have reported the therapeutic effects of oleuropein (OP) consumption on the early stage of diabetic nephropathy and diabetic cardiomyopathy. However, the efficacy of OP on the long-course of these diabetes complications has not been investigated. Therefore, in this study, to investigate the relieving effects of OP intake on these diseases, and to explore the underlying mechanisms, db\/db mice (17-week-old) were orally administrated with OP (200 mg\/kg bodyweight) for 15 weeks. We found that OP reduced expansion of the glomerular mesangial matrix, renal inflammation, renal fibrosis, and renal apoptosis. Meanwhile, OP treatment exerted cardiac anti-fibrotic, anti-inflammatory, and anti-apoptosis effects. Notably, transcriptomic and bioinformatic analyses indicated 290 and 267 differentially expressed genes in the kidney and heart replying to OP treatment, respectively. For long-course diabetic nephropathy, OP supplementation significantly upregulated the cyclic guanosine monophosphate-dependent protein kinase (cGMP\u2013PKG) signaling pathway. For long-course diabetic cardiomyopathy, p53 and cellular senescence signaling pathways were significantly downregulated in response to OP supplementation. Furthermore, OP treatment could significantly upregulate the transcriptional expression of the ATPase Na+\/K+ transporting subunit alpha 3, which was enriched in the cGMP\u2013PKG signaling pathway. In contrast, OP treatment could significantly downregulate the transcriptional expressions of cyclin-dependent kinase 1, G two S phase expressed protein 1, and cyclin B2, which were enriched in p53 and cellular senescence signal pathways; these genes were confirmed by qPCR validation. Overall, our findings demonstrate that OP ameliorated long-course diabetic nephropathy and cardiomyopathy in db\/db mice and highlight the potential benefits of OP as a functional dietary supplement in diabetes complications treatment.<\/jats:p>","DOI":"10.3390\/nu16060848","type":"journal-article","created":{"date-parts":[[2024,3,15]],"date-time":"2024-03-15T14:05:25Z","timestamp":1710511525000},"page":"848","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Oleuropein Supplementation Ameliorates Long-Course Diabetic Nephropathy and Diabetic Cardiomyopathy Induced by Advanced Stage of Type 2 Diabetes in db\/db Mice"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6545-0748","authenticated-orcid":false,"given":"Shujuan","family":"Zheng","sequence":"first","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"},{"name":"College of Biological and Food Engineering, Anhui Polytechnic University, Wuhu 241000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2094-8822","authenticated-orcid":false,"given":"Ruixuan","family":"Geng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingya","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8498-120X","authenticated-orcid":false,"given":"Seong-Gook","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Food Engineering, Solar Salt Research Center, Mokpo National University, Muangun 58554, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunlun","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"},{"name":"Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Ministry of Agriculture, Beijing 100083, China"},{"name":"Beijing Laboratory for Food Quality and Safety, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9309-2893","authenticated-orcid":false,"given":"Tao","family":"Tong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China"},{"name":"Key Laboratory of Safety Assessment of Genetically Modified Organism (Food Safety), Ministry of Agriculture, Beijing 100083, China"},{"name":"Beijing Laboratory for Food Quality and Safety, Beijing 100083, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1900\/RDS.2015.12.87","article-title":"Diabetic kidney disease: A syndrome rather than a single disease","volume":"12","author":"Piccoli","year":"2015","journal-title":"Rev. Diabet. Stud."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1330","DOI":"10.4103\/1319-2442.220877","article-title":"Clinicopathological study of nondiabetic renal disease in type 2 diabetic patients: A single center experience from India","volume":"28","author":"Kanodia","year":"2017","journal-title":"Saudi J. Kidney Dis. Transpl."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7378","DOI":"10.1080\/10408398.2022.2045895","article-title":"Understanding the mechanism underlying the anti-diabetic effect of dietary component: A focus on gut microbiota","volume":"63","author":"Zhao","year":"2023","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.2174\/1381612826666200728144200","article-title":"Fighting diabetes mellitus: Pharmacological and non-pharmacological approaches","volume":"26","author":"Wang","year":"2020","journal-title":"Curr. Pharm. Des."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Wang, Y.N., Liu, Q., Kang, S.K., Huang, K.L., and Tong, T. (2021). Dietary bioactive ingredients modulating the cAMP signaling in diabetes treatment. Nutrients, 13.","DOI":"10.3390\/nu13093038"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1016\/j.mcna.2023.03.004","article-title":"Diabetic kidney disease: An update","volume":"107","author":"Gupta","year":"2023","journal-title":"Med. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.pcad.2019.03.003","article-title":"Diabetic cardiomyopathy\u2014A comprehensive updated review","volume":"62","author":"Murtaza","year":"2019","journal-title":"Prog. Cardiovasc. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"6145","DOI":"10.1021\/acs.jafc.1c01404","article-title":"Efficacy and mechanisms of oleuropein in mitigating diabetes and diabetes complications","volume":"69","author":"Zheng","year":"2021","journal-title":"J. Agric. Food Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"3112","DOI":"10.1002\/ptr.6511","article-title":"Oleuropein: A natural antioxidant molecule in the treatment of metabolic syndrome","volume":"33","author":"Ahamad","year":"2019","journal-title":"Phyther. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/13813455.2019.1691603","article-title":"The olive constituent oleuropein exerts nephritic protective effects on diabetic nephropathy in db\/db mice","volume":"128","author":"Liu","year":"2022","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"398","DOI":"10.4103\/0253-7613.135951","article-title":"Oleuropein offers cardioprotection in rats with simultaneous type 2 diabetes and renal hypertension","volume":"46","author":"Nekooeian","year":"2014","journal-title":"Indian J. Pharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"383","DOI":"10.4236\/abb.2015.66038","article-title":"Heart histopathology and oxidative features in diabetic rats and protective effects of oleuropein","volume":"6","author":"Jemai","year":"2015","journal-title":"Adv. Biosci. Biotechnol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zheng, S.J., Wang, Y.N., Fang, J.J., Geng, R.X., Li, M.J., Zhao, Y.H., Kang, S.G., Huang, K.L., and Tong, T. (2021). Oleuropein ameliorates advanced stage of type 2 diabetes in db\/db mice by regulating gut microbiota. Nutrients, 13.","DOI":"10.3390\/nu13072131"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.mce.2014.11.018","article-title":"Protective effects of pioglitazone and\/or liraglutide on pancreatic \u03b2-cells in db\/db mice: Comparison of their effects between in an early and advanced stage of diabetes","volume":"400","author":"Kimura","year":"2015","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2442","DOI":"10.1111\/dom.13400","article-title":"Protective effects of the SGLT2 inhibitor luseogliflozin on pancreatic \u03b2-cells in db\/db mice: The earlier and longer, the better","volume":"20","author":"Kimura","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"122035","DOI":"10.1016\/j.envpol.2023.122035","article-title":"Chronic exposure to UVB induces nephritis and gut microbiota dysbiosis in mice based on the integration of renal transcriptome profiles and 16S rRNA sequencing data","volume":"333","author":"Geng","year":"2023","journal-title":"Environ. Pollut."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: A fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol., 15.","DOI":"10.1186\/s13059-014-0550-8"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"W316","DOI":"10.1093\/nar\/gkr483","article-title":"KOBAS 2.0: A web server for annotation and identification of enriched pathways and diseases","volume":"39","author":"Xie","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e2000015","DOI":"10.1002\/mnfr.202000015","article-title":"Anti-inflammatory and antioxidative properties of isoflavones provide renal protective effects distinct from those of dietary soy proteins against diabetic nephropathy","volume":"64","author":"Jheng","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.ijbiomac.2020.02.087","article-title":"Low molecular weight fucoidan alleviates diabetic nephropathy by binding fibronectin and inhibiting ECM-receptor interaction in human renal mesangial cells","volume":"150","author":"Wang","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e16225","DOI":"10.1097\/MD.0000000000016225","article-title":"Identification of miRNAs-genes regulatory network in diabetic nephropathy based on bioinformatics analysis","volume":"98","author":"Yang","year":"2019","journal-title":"Medicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1007\/s00125-011-2175-8","article-title":"Altered gap junctional communication and renal haemodynamics in Zucker fatty rat model of type 2 diabetes","volume":"54","author":"Takenaka","year":"2011","journal-title":"Diabetologia"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Chen, Y., and Burnett, J.C. (2018). Particulate guanylyl cyclase A\/cGMP signaling pathway in the kidney: Physiologic and therapeutic indications. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19041006"},{"key":"ref_25","first-page":"1476","article-title":"Pharmacological analysis of the iridoid oleuropein","volume":"22","author":"Petkov","year":"1972","journal-title":"Arzneimittelforschung"},{"key":"ref_26","unstructured":"Alonso, J. (2004). Tratado de Fitof\u00e1rmacos y Nutrac\u00e9uticos (Treaty of Phytopharmaceuticals and Nutraceuticals), Corpus Libros."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jsps.2018.11.015","article-title":"Olive leaves extract attenuates type II diabetes mellitus-induced testicular damage in rats: Molecular and biochemical study","volume":"27","author":"Soliman","year":"2019","journal-title":"Saudi Pharm. J."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1177\/1091581815619764","article-title":"A Comprehensive Toxicological Safety Assessment of an Extract of Olea Europaea L. Leaves (Bonolive\u2122)","volume":"35","author":"Clewell","year":"2016","journal-title":"Int. J. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1096\/fj.07-9574LSF","article-title":"Dose translation from animal to human studies revisited","volume":"22","author":"Nihal","year":"2008","journal-title":"FASEB J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1021\/jf903405e","article-title":"Identification of Throuba Thassos, a traditional Greek table olive variety, as a nutritional rich source of oleuropein","volume":"58","author":"Zoidou","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Porto, A.D., Brosol, G., Casarsa, V., Bulfone, L., Scandolin, L., Catena, C., and Sechi, L.A. (2022). The pivotal role of oleuropein in the anti-diabetic action of the mediterranean diet: A concise review. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14010040"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.phymed.2010.08.016","article-title":"Olive (Olea europaea) leaf extract effective in patients with stage-1 hypertension: Comparison with Captopril","volume":"18","author":"Susalit","year":"2011","journal-title":"Phytomedicine"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3389\/fendo.2013.00007","article-title":"Diabetic nephropathy: The role of inflammation in fibroblast activation and kidney fibrosis","volume":"4","author":"Kanasaki","year":"2013","journal-title":"Front. Endocrinol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1681\/ASN.2007091048","article-title":"The role of inflammatory cytokines in diabetic nephropathy","volume":"19","year":"2008","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"146154","DOI":"10.1155\/2012\/146154","article-title":"Inflammation in Diabetic Nephropathy","volume":"2012","author":"Lim","year":"2012","journal-title":"Mediators Inflamm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1681\/ASN.2009020227","article-title":"BASP1 promotes apoptosis in diabetic nephropathy","volume":"21","author":"Sanz","year":"2010","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.9734\/EJMP\/2017\/31953","article-title":"Antioxidant status and anti-inflammatory effects of oleuropein in streptozotocin-induced diabetic nephropathy in rats","volume":"18","author":"Karabag","year":"2017","journal-title":"European J. Med. Plants"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s00210-012-0730-6","article-title":"cGMP becomes a drug target","volume":"385","author":"Schlossmann","year":"2012","journal-title":"Naunyn Schmiedeberg\u2019s Arch. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"F671","DOI":"10.1152\/ajprenal.00042.2016","article-title":"The role of cGMP and its signaling pathways in kidney disease","volume":"311","author":"Shen","year":"2016","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_40","first-page":"229","article-title":"New pharmacological strategies to increase cGMP","volume":"67","author":"Burnett","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2320","DOI":"10.3390\/ijms16022320","article-title":"Cyclic nucleotide signalling in kidney fibrosis","volume":"16","author":"Schinner","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"R952","DOI":"10.1152\/ajpregu.1993.264.5.R952","article-title":"Attenuated glomerular cGMP production and renal vasodilation in streptozotocin-induced diabetic rats","volume":"264","author":"Wang","year":"1993","journal-title":"Am. J. Physiol.-Regul. Integr. Comp. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"F1151","DOI":"10.1152\/ajprenal.00596.2011","article-title":"Nicorandil as a novel therapy for advanced diabetic nephropathy in the eNOS-deficient mouse","volume":"302","author":"Tanabe","year":"2012","journal-title":"Am. J. Physiol. Renal Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"20420188221083530","DOI":"10.1177\/20420188221083530","article-title":"Role of inflammation in diabetic cardiomyopathy","volume":"13","author":"Ramesh","year":"2022","journal-title":"Ther. Adv. Endocrinol. Metab."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5129","DOI":"10.1038\/onc.2012.640","article-title":"Senescence and aging: The critical roles of p53","volume":"32","author":"Rufini","year":"2013","journal-title":"Oncogene"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.tcb.2007.04.004","article-title":"p53: New roles in metabolism","volume":"17","author":"Bensaad","year":"2007","journal-title":"Trends Cell Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1038\/nature03098","article-title":"Intrinsic tumour suppression","volume":"432","author":"Lowe","year":"2004","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"7715","DOI":"10.3892\/mmr.2017.7522","article-title":"Alteration of oxidative stress and inflammatory cytokines induces apoptosis in diabetic nephropathy","volume":"16","author":"Sha","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_49","first-page":"1799","article-title":"Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo","volume":"9","author":"Miyashita","year":"1994","journal-title":"Oncogene"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"H448","DOI":"10.1152\/ajpheart.00287.2018","article-title":"Cellular senescence links aging and diabetes in cardiovascular disease","volume":"315","author":"Shakeri","year":"2018","journal-title":"Am. J. Physiol. -Hear. Circ. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"716517","DOI":"10.3389\/fphar.2021.716517","article-title":"Senescence and type 2 diabetic cardiomyopathy: How young can you die of old age?","volume":"12","author":"Henson","year":"2021","journal-title":"Front. Pharmacol."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/6\/848\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:14:08Z","timestamp":1760105648000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/16\/6\/848"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,15]]},"references-count":51,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,3]]}},"alternative-id":["nu16060848"],"URL":"https:\/\/doi.org\/10.3390\/nu16060848","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,15]]}}}