{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T16:15:41Z","timestamp":1774541741012,"version":"3.50.1"},"reference-count":47,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"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>Spermidine is a natural autophagy-inducer and anti-aging compound. Herein, we investigated a potential autophagy-independent mechanism of spermidine, namely its capability to directly impede LDL oxidation, an early step in atherogenesis. In our in vitro-model, LDL oxidation was induced by the addition of CuCl2 in the presence of increasing concentrations of spermidine, and the degree of oxidation of the lipid, as well as of the protein part of LDL, was measured. We found that spermidine concentration-dependently inhibited the production of lipid hydroperoxides, malondialdehyde, and oxidation-specific immune epitopes in the LDL particle, associated with decreased relative electrophoretic mobilities, respectively. For example, the LPO content was significantly lower when LDL was oxidized in the presence of 500 \u00b5g\/mL spermidine (26.9 \u00b1 1.6 nmol\/mg LDL) than in the absence of spermidine (180.6 \u00b1 7.7 nmol\/mg LDL, p &lt; 0.0001). When oxLDL was obtained under increasing spermidine concentrations, its cytotoxicity in EA.hy926 cells concentration-dependently decreased. Quantum chemical calculations show that the reaction between spermidine and hydroxyl radicals is exergonic. We conclude that spermidine is a direct inhibitor of LDL oxidation due to its capability to scavenge hydroxyl radicals. Thus, spermidine supplementation might be a suitable tool to impede atherogenesis and associated (cardio)vascular diseases. Further prospective clinical studies are needed to evaluate the potential atheroprotective\/health-promoting effects of spermidine-rich diets.<\/jats:p>","DOI":"10.3390\/molecules30040955","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T05:34:26Z","timestamp":1739943266000},"page":"955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Natural Polyamine Spermidine Inhibits the In Vitro Oxidation of LDL"],"prefix":"10.3390","volume":"30","author":[{"given":"Christine","family":"Rossmann","sequence":"first","affiliation":[{"name":"Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Azra","family":"Darko","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerd","family":"Kager","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard","family":"Ledinski","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7171-9539","authenticated-orcid":false,"given":"Willibald","family":"Wonisch","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Blood Group Serology and Transfusion Medicine, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seth","family":"Hallstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria"},{"name":"Division of Biomedical Research and Translational Medicine, Medical University of Vienna, 1090 Vienna, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilbert","family":"Reibnegger","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5494-8890","authenticated-orcid":false,"given":"Margret","family":"Paar","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1410-1844","authenticated-orcid":false,"given":"Gerhard","family":"Cvirn","sequence":"additional","affiliation":[{"name":"Division of Medicinal Chemistry, Otto Loewi Research Center, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"eaan2788","DOI":"10.1126\/science.aan2788","article-title":"Spermidine in health and disease","volume":"359","author":"Madeo","year":"2018","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1038\/s41556-024-01468-x","article-title":"Spermidine is essential for fasting-mediated autophagy and longevity","volume":"26","author":"Hofer","year":"2024","journal-title":"Nat. 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