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In fact, anti-inflammatory and immune-suppressive drugs are applied to limit the immune response to treat inflammatory diseases. Flavonoids are plant-derived polyphenols extensively investigated for their anti-inflammatory and antioxidant properties in inflammatory diseases. Studies applying isolated compounds as well as using supplements as nutraceuticals based on flavonoids have been conducted. Our review systematically analyzed the top five studied flavonoids between 2020 and 2025: quercetin (1742 articles), kaempferol (642), luteolin (589), apigenin (419), and epicatechin (354), highlighting their major therapeutic applications in diseases affecting the liver (12%), nervous system (11%), and lungs (10%). Mechanistically, these compounds act as multi-target agents mainly by inhibiting NF-\u03baB and inducing Nrf2-dependent antioxidant programs. Application of advanced delivery systems, which increase oral bioavailability by up to 20-fold, overcomes pharmacokinetic bottlenecks. Clinical highlights demonstrated promising therapeutic effects, including reduced intrahepatic lipid accumulation in non-alcoholic fatty liver disease patients following quercetin supplementation (11.5% to 9.6%) and accelerated SARS-CoV-2 clearance after quercetin phytosome administration. The translation of flavonoids into standardized clinical therapies remains limited by the lack of large-scale, well-controlled clinical trials.<\/jats:p>","DOI":"10.3390\/foods15122159","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T15:00:48Z","timestamp":1781535648000},"page":"2159","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Flavonoids as Nutraceuticals to Treat Inflammatory Diseases: Focusing on Quercetin, Kaempferol, Luteolin, Apigenin, Epicatechin and Their Effects on Hepatic, Nervous, and Pulmonary Systems"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4099-3492","authenticated-orcid":false,"given":"Maiara","family":"Piva","sequence":"first","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy and Cancer, Department of Immunology, Parasitology, and General Pathology, Center of Biological Sciences, Londrina State University, Londrina 86057-970, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6751-950X","authenticated-orcid":false,"given":"Geovana","family":"Martelossi-Cebinelli","sequence":"additional","affiliation":[{"name":"Laboratory of Pain, Inflammation, Neuropathy and Cancer, Department of Immunology, Parasitology, and General Pathology, Center of Biological Sciences, Londrina State University, Londrina 86057-970, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraia","family":"Mendes-Pierotti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Center of Health Science, Londrina State University, Londrina 86038-440, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9356-0797","authenticated-orcid":false,"given":"Willian H.","family":"Chinen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Center of Health Science, Londrina State University, Londrina 86038-440, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro H. F.","family":"Cardines","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biotechnology, Center of Exact Sciences, Londrina State University, Londrina 86057-970, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1096-0876","authenticated-orcid":false,"given":"Renata M.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Center of Health Science, Londrina State University, Londrina 86038-440, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra R.","family":"Georgetti","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Center of Health Science, Londrina State University, Londrina 86038-440, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7109-7191","authenticated-orcid":false,"given":"Marcela M.","family":"Baracat","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Center of Health Science, Londrina State University, Londrina 86038-440, PR, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0842-9130","authenticated-orcid":false,"given":"Fabiana T. M. 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