{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:57:44Z","timestamp":1792799864038,"version":"4.5.0"},"reference-count":155,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T00:00:00Z","timestamp":1773792000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Cardiorenal syndrome (CRS) represents a complex clinical entity characterized by the bidirectional dysfunction of the heart and kidneys. Despite advances in pharmacological therapy, CRS remains associated with high morbidity and mortality. Pathophysiological drivers, including oxidative stress, chronic inflammation, and mitochondrial derangements, create a self-perpetuating cycle of organ damage that necessitates multitarget therapeutic approaches. Objective: This review synthesizes current preclinical evidence regarding the protective roles of plant-derived polyphenols\u2014specifically bergamot, curcumin, quercetin, catechins, and resveratrol\u2014in mitigating the cardiorenal continuum. Methods: An analysis of recent literature was conducted, focusing on the molecular mechanisms by which these bioactives modulate redox balance, inflammatory signaling, and mitochondrial homeostasis in experimental models of CRS. Results: Polyphenols act at the crossroads of several stress-response pathways. Key mechanisms include the activation of the Nrf2\/HO-1 axis to enhance endogenous antioxidant defenses, the suppression of the NLRP3 inflammasome to attenuate systemic \u201cinflammaging\u201d, and the preservation of mitochondrial quality through SIRT1\/PINK1\/Parkin-mediated mitophagy. Furthermore, emerging evidence highlights the role of polyphenols in modulating the gut-kidney-heart axis by reducing microbiota-derived uremic toxins. Conclusions: Preclinical data suggest that polyphenols are potent multifunctional agents capable of breaking the feedback loops of cardiorenal injury. While bioavailability remains a significant translational challenge, novel nano-delivery systems and synthetic analogs offer promising strategies for clinical application. Integrating these bioactives into CRS management could provide a decisive adjunctive strategy to improve metabolic homeostasis and prevent end-stage organ failure.<\/jats:p>","DOI":"10.3390\/nu18060955","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T14:14:05Z","timestamp":1773843245000},"page":"955","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Nature\u2019s Bioactives in Cardiorenal Syndrome: Polyphenols at the Crossroads\u2014Preclinical Insights into Redox, Inflammation, and Mitochondrial Protection"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6767-8823","authenticated-orcid":false,"given":"Caterina","family":"Carollo","sequence":"first","affiliation":[{"name":"Department of Health Promotion, Mother and Child Health, Internal and Specialistic Medicine, Unit of Nephrology and Dialysis, Policlinico \u201cP. Giaccone\u201d, University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8245-9219","authenticated-orcid":false,"given":"Maria Elena","family":"Ciuppa","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Health, Internal and Specialistic Medicine, Unit of Nephrology and Dialysis, Policlinico \u201cP. Giaccone\u201d, University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Sorce","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Health, Internal and Specialistic Medicine, Unit of Nephrology and Dialysis, Policlinico \u201cP. Giaccone\u201d, University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Evola","sequence":"additional","affiliation":[{"name":"Catheterization Laboratory, Department of Medicine and Cardiology, Azienda Ospedaliera Universitaria Policlinico \u201cP. Giaccone\u201d, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4934-0818","authenticated-orcid":false,"given":"Emanuele","family":"Cirafici","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Health, Internal and Specialistic Medicine, Unit of Nephrology and Dialysis, Policlinico \u201cP. Giaccone\u201d, University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Giovanna","family":"Vario","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Health, Internal and Specialistic Medicine, Unit of Nephrology and Dialysis, Policlinico \u201cP. Giaccone\u201d, University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4893-8128","authenticated-orcid":false,"given":"Roberta","family":"Scimeca","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Health, Internal and Specialistic Medicine, Unit of Nephrology and Dialysis, Policlinico \u201cP. Giaccone\u201d, University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7491-568X","authenticated-orcid":false,"given":"Rosalia Lo","family":"Presti","sequence":"additional","affiliation":[{"name":"Department of Psychology, Educational Science and Human Movement, University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8500-8671","authenticated-orcid":false,"given":"Giuseppe","family":"Mul\u00e8","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Health, Internal and Specialistic Medicine, Unit of Nephrology and Dialysis, Policlinico \u201cP. Giaccone\u201d, University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregorio","family":"Caimi","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Health, Internal and Specialistic Medicine, Unit of Nephrology and Dialysis, Policlinico \u201cP. Giaccone\u201d, University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.1016\/j.jacc.2008.07.051","article-title":"Cardiorenal syndrome","volume":"52","author":"Ronco","year":"2008","journal-title":"J. Am. Coll. 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