{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:25:46Z","timestamp":1784215546290,"version":"3.55.0"},"reference-count":94,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T00:00:00Z","timestamp":1636848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministry of Education, Universities and Research","doi-asserted-by":"publisher","award":["PON-MIUR 03PE000_78_1, PONMIUR 03PE000_78_2, PRIR AGRINFRA CALABRIA"],"award-info":[{"award-number":["PON-MIUR 03PE000_78_1, PONMIUR 03PE000_78_2, PRIR AGRINFRA CALABRIA"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Doxorubicin (Doxo) is a widely used antineoplastic drug which often induces cardiomyopathy, leading to congestive heart failure through the intramyocardial production of reactive oxygen species (ROS). Icariin (Ica) is a flavonoid isolated from Epimedii Herba (Berberidaceae). Some reports on the pharmacological activity of Ica explained its antioxidant and cardioprotective effects. The aim of our study was to assess the protective activities of Ica against Doxo-detrimental effects on rat heart-tissue derived embryonic cardiac myoblasts (H9c2 cells) and to identify, at least in part, the molecular mechanisms involved. Our results showed that pretreatment of H9c2 cells with 1 \u03bcM and 5 \u03bcM of Ica, prior to Doxo exposure, resulted in an improvement in cell viability, a reduction in ROS generation, the prevention of mitochondrial dysfunction and mPTP opening. Furthermore, for the first time, we identified one feasible molecular mechanism through which Ica could exerts its cardioprotective effects. Indeed, our data showed a significant reduction in Caveolin-1(Cav-1) expression levels and a specific inhibitory effect on phosphodiesterase 5 (PDE5a) activity, improving mitochondrial function compared to Doxo-treated cells. Besides, Ica significantly prevented apoptotic cell death and downregulated the main pro-autophagic marker Beclin-1 and LC3 lipidation rate, restoring physiological levels of activation of the protective autophagic process. These results suggest that Ica might have beneficial cardioprotective effects in attenuating cardiotoxicity in patients requiring anthracycline chemotherapy through the inhibition of oxidative stress and, in particular, through the modulation of Cav-1 expression levels and the involvement of PDE5a activity, thereby leading to cardiac cell survival.<\/jats:p>","DOI":"10.3390\/nu13114070","type":"journal-article","created":{"date-parts":[[2021,11,14]],"date-time":"2021-11-14T20:51:53Z","timestamp":1636923113000},"page":"4070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Icariin Protects H9c2 Rat Cardiomyoblasts from Doxorubicin-Induced Cardiotoxicity: Role of Caveolin-1 Upregulation and Enhanced Autophagic Response"],"prefix":"10.3390","volume":"13","author":[{"given":"Miriam","family":"Scicchitano","sequence":"first","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Carresi","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saverio","family":"Nucera","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0401-4027","authenticated-orcid":false,"given":"Stefano","family":"Ruga","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Maiuolo","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Macr\u00ec","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Scarano","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Bosco","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7106-5595","authenticated-orcid":false,"given":"Rocco","family":"Mollace","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9091-1806","authenticated-orcid":false,"given":"Antonio","family":"Cardamone","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Rita","family":"Coppoletta","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenza","family":"Guarnieri","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Caterina","family":"Zito","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Bava","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Cariati","sequence":"additional","affiliation":[{"name":"Institute of Research for Food Safety and Health (IRC-FSH), Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4192-3891","authenticated-orcid":false,"given":"Marta","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University \u201cMagna Graecia\u201d of Catanzaro, 88100 Catanzaro, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ejcsup.2014.03.002","article-title":"Cardiovascular disease after cancer therapy","volume":"12","author":"Aleman","year":"2014","journal-title":"Eur. 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