{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:57:55Z","timestamp":1785430675478,"version":"3.56.0"},"reference-count":99,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Graduate Studies and Scientific Research at Qassim University","award":["QU-APC-2026"],"award-info":[{"award-number":["QU-APC-2026"]}]},{"award":["QU-APC-2026"],"award-info":[{"award-number":["QU-APC-2026"]}],"id":[{"id":"https:\/\/ror.org\/01wsfe280","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vet. Sci.","Veterinary Sciences"],"abstract":"<jats:p>Mammary gland inflammation, clinically expressed as mastitis in dairy ruminants and lactating women, arises from a self-amplifying loop of pathogen sensing, oxidative stress and innate immune activation, and remains a leading driver of antibiotic use, milk-quality loss and morbidity. Mounting pressure to reduce antimicrobial dependence has refocused attention on flavonoids\u2014structurally diverse plant polyphenols with multi-target bioactivity, derived mainly from in vitro and rodent mastitis models. This review integrates contemporary evidence on the six principal flavonoid subclasses within a unifying molecular framework. Across subclasses, flavonoids converge on shared targets: the TLR4\u2013MyD88\u2013NF-\u03baB axis, MAPK cascades, the Keap1\u2013Nrf2\u2013ARE antioxidant pathway, the NLRP3 inflammasome and tight-junction proteins of the blood\u2013milk barrier. Less canonical mechanisms\u2014m6A epitranscriptomic regulation, ferroptosis suppression, AhR signalling, anti-virulence binding to bacterial enzymes such as IGPD, and gut-microbiota-driven remodelling of the gut\u2013mammary axis\u2014expand the pharmacological landscape. We additionally appraise the subclasses comparatively, identifying flavanones and the flavone baicalin as carrying the strongest translational evidence, and examine the conflicting findings, model limitations, and delivery, residue and regulatory barriers that currently separate mechanistic promise from on-farm application. We outline structure\u2013activity considerations and translational priorities, and position flavonoids as mechanism-rich, antibiotic-sparing candidates for the prevention and adjunctive management of mammary gland inflammation in dairy ruminants.<\/jats:p>","DOI":"10.3390\/vetsci13080743","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:54:26Z","timestamp":1785153266000},"page":"743","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Flavonoids in Alleviating Mammary Gland Inflammation: A Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0268-1167","authenticated-orcid":false,"given":"Abdul","family":"Qadeer","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, Shandong Xiehe University, Jinan 250109, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3796-9590","authenticated-orcid":false,"given":"Mohamed","family":"Tharwat","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences, College of Veterinary Medicine, Qassim University, P.O. Box 6622, Buraidah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6632-0646","authenticated-orcid":false,"given":"Ibrahim F.","family":"Halawani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21974, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6930-5214","authenticated-orcid":false,"given":"Fuad M.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21974, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6688-0106","authenticated-orcid":false,"given":"Khalid J.","family":"Alzahrani","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taif University, Taif 21974, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7267-4301","authenticated-orcid":false,"given":"Fahad A.","family":"Alshanbari","sequence":"additional","affiliation":[{"name":"Department of Medical Biosciences, College of Veterinary Medicine, Qassim University, P.O. Box 6622, Buraidah 51452, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5890-2996","authenticated-orcid":false,"given":"Muhammad Zahoor","family":"Khan","sequence":"additional","affiliation":[{"name":"College of Agriculture and Biology, Liaocheng University, Liaocheng 252000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Li, Y., Wang, M., Liu, W., Geng, M., Asiri, M., Alzahrani, F.M., Alzahrani, K.J., Ma, Q., Wang, C., and Khan, M.Z. (2025). Targeting the Gut\u2013Mammary Axis for Understanding Mastitis Pathogenesis and Therapeutic Strategies. Vet. 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