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Ubiquitous in plants, these polyphenolic compounds play crucial roles in pigmentation defense and are well recognized for their protective effects against cancer, metabolic, and neurodegenerative disorders. The ability of flavonoids to interact with diverse molecular targets and regulate critical signaling pathways underscores their relevance in preclinical and clinical settings. The present review critically consolidates recent advances in the therapeutic profile of flavonoids, covering their biosynthetic pathways, molecular structures, and extraction methodologies. Emphasis is given on their pharmacological effects in cancer, metabolic, microbial, respiratory, and nutraceutical applications. The mechanistic basis of their multi\u2010targeted actions is also discussed and supported by emerging clinical data. By outlining the current advancements, key challenges, and future perspectives, this review advocates for incorporating flavonoid\u2010based interventions into clinical practice and highlights their potential as effective alternatives to conventional therapies.<\/jats:p>","DOI":"10.1002\/ptr.70035","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T01:54:30Z","timestamp":1752544470000},"page":"3833-3867","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Natural Products in the 21<sup>st<\/sup> Century: Revolutionizing Therapeutics With Flavonoids as Key Phytometabolites"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-0171-0915","authenticated-orcid":false,"given":"P.","family":"Krishna","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences and Natural Products Central University of Punjab  Bathinda India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5469-6050","authenticated-orcid":false,"given":"Aatif","family":"Subhan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Natural Products Central University of Punjab  Bathinda India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1486-1201","authenticated-orcid":false,"given":"Khushi","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Natural Products Central University of Punjab  Bathinda India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0153-2941","authenticated-orcid":false,"given":"Avadh","family":"Biharee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Natural Products Central University of Punjab  Bathinda India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7668-462X","authenticated-orcid":false,"given":"Suresh","family":"Thareja","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences and Natural Products Central University of Punjab  Bathinda India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,14]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jare.2020.01.002"},{"key":"e_1_2_18_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2024.101992"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2017.1332602"},{"key":"e_1_2_18_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2020.e03381"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2019.152853"},{"key":"e_1_2_18_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants9121688"},{"key":"e_1_2_18_8_1","unstructured":"Agency B. 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