{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:09:41Z","timestamp":1790611781558,"version":"4.1.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T00:00:00Z","timestamp":1612224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Diabetic cardiomyopathy (DCM) is one of the major causes of death in diabetic patients. Its pathogenesis involves inflammation and fibrosis that damages the heart tissue and impairs cardiac function. Interleukin (IL)-17, a pro-inflammatory cytokine that plays an important role in a variety of chronic inflammatory processes can serve as an attractive therapeutic target. Anthocyanin, a water-soluble natural pigment, possesses impressive anti-inflammatory activity. However, its role in DCM is unclear. Hence, we investigated the protective effect of anthocyanin on the cardiovascular complications of diabetes using a mouse type 1 diabetes mellitus model induced by streptozotocin. Cardiac function and structural alterations in diabetic mice were tested by echocardiography, hematoxylin and eosin staining, and Masson trichrome staining. Immunohistochemistry was performed to evaluate the distribution and deposition of IL-17 and collagen I and III from the left ventricular tissues of diabetic mice. Cell viability was measured using the methyl thiazolyl tetrazolium assay. Protein levels of IL-17, tumor necrosis factor \u03b1, IL-1\u03b2, and IL-6 were determined using enzyme-linked immunosorbent assay. IL-17 and collagen I and III were detected by western blotting and immunofluorescence, and their mRNA levels were quantified using quantitative reverse transcription PCR. We observed that anthocyanin lowered blood glucose, improved cardiac function, and alleviated inflammation and fibrosis in the heart tissue of diabetic mice. Meanwhile, anthocyanin reduced the expression of IL-17 in high-glucose-treated cardiac fibroblasts and exhibited an anti-inflammatory effect. Deposition of collagen I and III was also decreased by anthocyanin, suggesting that anthocyanin contributes to alleviating myocardial fibrosis. In summary, anthocyanin could protect cardiac function and inhibit IL-17-related inflammation and fibrosis, which indicates its therapeutic potential in the treatment of diabetes mellitus-related complications.<\/jats:p>","DOI":"10.3389\/fphar.2020.593633","type":"journal-article","created":{"date-parts":[[2021,2,2]],"date-time":"2021-02-02T21:20:59Z","timestamp":1612300859000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":31,"title":["Anthocyanin Protects Cardiac Function and Cardiac Fibroblasts From High-Glucose Induced Inflammation and Myocardial Fibrosis by Inhibiting IL-17"],"prefix":"10.3389","volume":"11","author":[{"given":"Er","family":"Yue","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baofeng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2136","DOI":"10.1016\/j.biopha.2018.11.064","article-title":"Curcumin augments the cardioprotective effect of metformin in an experimental model of type I diabetes mellitus; Impact of Nrf2\/HO-1 and JAK\/STAT pathways","volume":"109","author":"Abdelsamia","year":"2019","journal-title":"Biomed. Pharmacother"},{"key":"B2","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.1365-2249.2007.03356.x","article-title":"The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease","volume":"148","author":"Afzali","year":"2007","journal-title":"Clin. Exp. Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1016\/j.jaut.2012.12.013","article-title":"Overexpression of microRNA-21 is associated with elevated pro-inflammatory cytokines in dominant-negative TGF-\u03b2 receptor type II mouse","volume":"41","author":"Ando","year":"2013","journal-title":"J. Autoimmun"},{"key":"B4","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1016\/j.molmed.2016.01.001","article-title":"IL-17 in chronic inflammation: from Discovery to targeting","volume":"22","author":"Beringer","year":"2016","journal-title":"Trends Mol. Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1412","DOI":"10.4049\/jimmunol.1800189","article-title":"miR-340 alleviates psoriasis in mice through direct targeting of IL-17A","volume":"201","author":"Bian","year":"2018","journal-title":"J. Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.3390\/nu11092107","article-title":"Dietary anthocyanins and human health","volume":"11","author":"Blesso","year":"2019","journal-title":"Nutrients"},{"key":"B7","doi-asserted-by":"publisher","first-page":"3394","DOI":"10.3390\/ijms20143394","article-title":"Th17 cells and the IL-23\/IL-17 axis in the pathogenesis of periodontitis and immune-mediated inflammatory diseases","volume":"20","author":"Bunte","year":"2019","journal-title":"Int. J. Mol. Sci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1016\/j.jnutbio.2015.12.020","article-title":"Purple rice anthocyanin extract protects cardiac function in STZ-induced diabetes rat hearts by inhibiting cardiac hypertrophy and fibrosis","volume":"31","author":"Chen","year":"2016","journal-title":"J. Nutr. Biochem"},{"key":"B9","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.redox.2018.05.012","article-title":"Cyanidin and delphinidin modulate inflammation and altered redox signaling improving insulin resistance in high fat-fed mice","volume":"18","author":"Daveri","year":"2018","journal-title":"Redox Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1161\/CIRCRESAHA.118.314665","article-title":"Diabetic cardiomyopathy","volume":"124","author":"Dillmann","year":"2019","journal-title":"Circ. Res"},{"key":"B11","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1002\/kjm2.12229","article-title":"MicroRNA-155 deficiency attenuates inflammation and oxidative stress in experimental autoimmune prostatitis in a TLR4-dependent manner","volume":"36","author":"Fu","year":"2020","journal-title":"Kaohsiung J. Med. Sci"},{"key":"B12","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.cellimm.2015.05.007","article-title":"The paradoxical role of IL-17 in atherosclerosis","volume":"297","author":"Gong","year":"2015","journal-title":"Cell. Immunol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1177\/0960327112450885","article-title":"Diabetic cardiomyopathy: pathophysiological mechanisms and cardiac dysfuntion","volume":"32","author":"Goyal","year":"2013","journal-title":"Hum. Exp. Toxicol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1093\/jnci\/59.3.941","article-title":"In vitro studies of chemical mutagens and carcinogens. I. Stability studies in cell culture medium","volume":"59","author":"Jensen","year":"1977","journal-title":"J. Natl. Cancer Inst"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2658","DOI":"10.1161\/ATVBAHA.114.304108","article-title":"Interleukin 17 drives vascular inflammation, endothelial dysfunction, and arterial hypertension in psoriasis-like skin disease","volume":"34","author":"Karbach","year":"2014","journal-title":"Arterioscler. Thromb. Vasc. Biol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e2565","DOI":"10.1038\/cddis.2016.490","article-title":"IL-17-mediated mitochondrial dysfunction impairs apoptosis in rheumatoid arthritis synovial fibroblasts through activation of autophagy","volume":"8","author":"Kim","year":"2017","journal-title":"Cell Death Dis"},{"key":"B17","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s12933-019-0816-2","article-title":"SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart","volume":"18","author":"Li","year":"","journal-title":"Cardiovasc. Diabetol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.1007\/s10620-019-05969-w","article-title":"Role of interleukin-17 in pathogenesis of intestinal fibrosis in mice","volume":"65","author":"Li","year":"","journal-title":"Dig. Dis. Sci"},{"key":"B19","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1016\/j.jacc.2011.10.863","article-title":"Interleukin-17A contributes to myocardial ischemia\/reperfusion injury by regulating cardiomyocyte apoptosis and neutrophil infiltration","volume":"59","author":"Liao","year":"2012","journal-title":"J. Am. Coll. Cardiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1007\/s00441-018-2974-z","article-title":"Salutary effect of fenofibrate on type 1 diabetic retinopathy via inhibiting oxidative stress-mediated Wnt\/\u03b2-catenin pathway activation","volume":"376","author":"Liu","year":"","journal-title":"Cell Tissue Res"},{"key":"B21","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1002\/glia.23530","article-title":"MiR-409-3p and MiR-1896 co-operatively participate in IL-17-induced inflammatory cytokine production in astrocytes and pathogenesis of EAE mice via targeting SOCS3\/STAT3 signaling","volume":"67","author":"Liu","year":"","journal-title":"Glia"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1180","DOI":"10.1016\/j.jhep.2014.12.011","article-title":"Mirtoselect, an anthocyanin-rich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE(\u2217)3Leiden mice","volume":"62","author":"Morrison","year":"2015","journal-title":"J. Hepatol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1111\/j.1365-2567.2009.03240.x","article-title":"Interleukin-17 and its target genes: mechanisms of interleukin-17 function in disease","volume":"129","author":"Onishi","year":"2010","journal-title":"Immunology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.tips.2018.02.010","article-title":"Emerging actors in diabetic cardiomyopathy: heartbreaker biomarkers or therapeutic targets?","volume":"39","author":"Palomer","year":"2018","journal-title":"Trends Pharmacol. Sci"},{"key":"B25","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1158\/2326-6066.CIR-15-0091","article-title":"Dietary consumption of black raspberries or their anthocyanin constituents alters innate immune cell trafficking in esophageal cancer","volume":"4","author":"Peiffer","year":"2016","journal-title":"Cancer Immunol Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/0022-2828(81)90318-7","article-title":"Depressed cardiac sarcoplasmic reticular function from diabetic rats","volume":"13","author":"Penpargkul","year":"1981","journal-title":"J. Mol. Cell. Cardiol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"108874","DOI":"10.1016\/j.cbi.2019.108874","article-title":"Saikosaponin A ameliorates nasal inflammation by suppressing IL-6\/ROR-\u03b3t\/STAT3\/IL-17\/NF-\u03baB pathway in OVA-induced allergic rhinitis","volume":"315","author":"Piao","year":"2020","journal-title":"Chem. Biol. Interact"},{"key":"B28","doi-asserted-by":"publisher","first-page":"243","DOI":"10.3389\/fcell.2020.00243","article-title":"LncRNA-MIAT-mediated miR-214-3p silencing is responsible for IL-17 production and cardiac fibrosis in diabetic cardiomyopathy","volume":"8","author":"Qi","year":"2020","journal-title":"Front Cell Dev Biol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"728741","DOI":"10.1155\/2015\/728741","article-title":"An altered pattern of myocardial histopathological and molecular changes underlies the different characteristics of type-1 and type-2 diabetic cardiac dysfunction","volume":"2015","author":"Radovits","year":"2015","journal-title":"J Diabetes Res"},{"key":"B30","doi-asserted-by":"publisher","first-page":"716","DOI":"10.2337\/db11-0477","article-title":"Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy","volume":"61","author":"Rajesh","year":"2012","journal-title":"Diabetes"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1268","DOI":"10.1161\/01.res.49.6.1268","article-title":"Myocardial composition and function in diabetes. The effects of chronic insulin use","volume":"49","author":"Regan","year":"1981","journal-title":"Circ. Res"},{"key":"B32","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.phrs.2012.11.008","article-title":"Blueberry polyphenol-enriched soybean flour reduces hyperglycemia, body weight gain and serum cholesterol in mice","volume":"68","author":"Roopchand","year":"2013","journal-title":"Pharmacol. Res"},{"key":"B33","doi-asserted-by":"crossref","first-page":"5445","DOI":"10.4049\/jimmunol.150.12.5445","article-title":"CTLA-8, cloned from an activated T cell, bearing AU-rich messenger RNA instability sequences, and homologous to a herpesvirus saimiri gene","volume":"150","author":"Rouvier","year":"1993","journal-title":"J. Immunol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1177\/1074248419876632","article-title":"The potential role of undercarboxylated osteocalcin upregulation in microvascular insufficiency in a rat model of diabetic cardiomyopathy","volume":"25","author":"Sadek","year":"2020","journal-title":"J. Cardiovasc. Pharmacol. Therapeut"},{"key":"B35","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.jaci.2016.07.025","article-title":"MicroRNA-146a suppresses IL-17-mediated skin inflammation and is genetically associated with psoriasis","volume":"139","author":"Srivastava","year":"2017","journal-title":"J. Allergy Clin. Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"3129","DOI":"10.1002\/ptr.6485","article-title":"Anthocyanidin attenuates myocardial ischemia induced injury via inhibition of ROS-JNK-Bcl-2 pathway: new mechanism of anthocyanidin action","volume":"33","author":"Syeda","year":"2019","journal-title":"Phytother Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.jdermsci.2016.10.007","article-title":"Potential role of IL-17-producing CD4\/CD8 double negative \u03b1\u03b2 T cells in psoriatic skin inflammation in a TPA-induced STAT3C transgenic mouse model","volume":"85","author":"Ueyama","year":"2017","journal-title":"J. Dermatol. Sci"},{"key":"B38","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.cellsig.2011.10.010","article-title":"Interleukin-17A stimulates cardiac fibroblast proliferation and migration via negative regulation of the dual-specificity phosphatase MKP-1\/DUSP-1","volume":"24","author":"Valente","year":"2012","journal-title":"Cell. Signal"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1038\/s41419-018-1029-4","article-title":"Silencing long non-coding RNA Kcnq1ot1 alleviates pyroptosis and fibrosis in diabetic cardiomyopathy","volume":"9","author":"Yang","year":"2018","journal-title":"Cell Death Dis"},{"key":"B40","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1016\/j.omtn.2019.06.026","article-title":"A novel circular RNA mediates pyroptosis of diabetic cardiomyopathy by functioning as a competing endogenous RNA","volume":"17","author":"Yang","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"B41","doi-asserted-by":"publisher","first-page":"286","DOI":"10.1016\/j.phymed.2018.09.223","article-title":"Anthocyanin is involved in the activation of pyroptosis in oral squamous cell carcinoma","volume":"56","author":"Yue","year":"2019","journal-title":"Phytomedicine"},{"key":"B42","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.yjmcc.2018.01.001","article-title":"Ablation of interleukin-17 alleviated cardiac interstitial fibrosis and improved cardiac function via inhibiting long non-coding RNA-AK081284 in diabetic mice","volume":"115","author":"Zhang","year":"2018","journal-title":"J. Mol. Cell. Cardiol"},{"key":"B43","first-page":"1843","article-title":"miR-125a-3p decreases levels of interlukin-17 and suppresses renal fibrosis via down-regulating TGF-\u03b21 in systemic lupus erythematosus mediated Lupus nephritic mice","volume":"11","author":"Zhang","year":"2019","journal-title":"Am J Transl Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1105","DOI":"10.1007\/s00109-014-1176-8","article-title":"IL-17A promotes ventricular remodeling after myocardial infarction","volume":"92","author":"Zhou","year":"2014","journal-title":"J. Mol. Med"},{"key":"B45","doi-asserted-by":"publisher","first-page":"4899","DOI":"10.1096\/fj.201701242RR","article-title":"IL-17 induces cellular stress microenvironment of melanocytes to promote autophagic cell apoptosis in vitiligo","volume":"32","author":"Zhou","year":"2018","journal-title":"Faseb. J"},{"key":"B46","doi-asserted-by":"publisher","first-page":"4172","DOI":"10.1080\/21691401.2019.1687492","article-title":"Astragaloside-IV protects H9C2(2-1) cardiomyocytes from high glucose-induced injury via miR-34a-mediated autophagy pathway","volume":"47","author":"Zhu","year":"2019","journal-title":"Artif Cells Nanomed Biotechnol"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2020.593633\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,20]],"date-time":"2023-10-20T02:24:40Z","timestamp":1697768680000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2020.593633\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,2]]},"references-count":46,"alternative-id":["10.3389\/fphar.2020.593633"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2020.593633","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,2]]},"article-number":"593633"}}