{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:52:50Z","timestamp":1785412370170,"version":"3.56.0"},"reference-count":206,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ANID Chile","award":["3240059"],"award-info":[{"award-number":["3240059"]}]},{"award":["3240059"],"award-info":[{"award-number":["3240059"]}],"id":[{"id":"https:\/\/ror.org\/02ap3w078","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Universidad de La Frontera, Temuco, Chile"},{"id":[{"id":"https:\/\/ror.org\/04v0snf24","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Dihydromyricetin (DHM), a naturally occurring flavanonol predominantly found in medicinal plants like Ampelopsis grossedentata, has emerged as a promising source of natural antioxidants with multi-target pharmacological activities relevant to drug discovery. DHM exhibits a strong redox-modulating capacity, effectively attenuating oxidative stress and inflammation central drivers of chronic disease pathogenesis. Beyond direct radical scavenging, DHM regulates multiple redox-sensitive and kinase-mediated signalling pathways, thereby influencing key cellular processes involved in disease initiation and progression. This review synthesizes current evidence on the therapeutic potential of DHM, critically evaluating its mechanistic basis and translational prospects, with emphasis on its dual redox-driven and kinase-mediated modes of action. We detail its roles in metabolic disorders such as diabetes, obesity, and liver diseases, neuroprotection, cardio protection, and cancer prevention, focusing on the modulation of critical networks such as AMPK, PI3K\/Akt, MAPK, NF-\u03baB, and Nrf2. The interplay between these pathways underpins DHM\u2019s efficacy across disease models. Furthermore, we highlight structure\u2013activity relationship (SAR) analyses and molecular modelling studies that elucidate how the flavanonol scaffold, hydroxylation pattern, and stereochemistry of DHM govern its biological activities and target engagement. Key pharmacokinetic limitations, advances in extraction techniques, bioavailability challenges, and emerging formulation strategies including advanced delivery systems are discussed to address translational hurdles. Despite compelling preclinical data, the clinical translation of DHM remains constrained by limited human studies and incomplete mechanistic resolution. This review underscores the need for integrated pharmacological studies and innovative delivery approaches to translate the multifaceted promise of DHM into viable clinical interventions.<\/jats:p>","DOI":"10.3390\/ijms27104626","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:06:07Z","timestamp":1779365167000},"page":"4626","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanistic Insights into Dihydromyricetin: Redox Modulation and Kinase-Mediated Control of Disease Pathogenesis"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5612-4027","authenticated-orcid":false,"given":"Oluwatoyin Adenike","family":"Fabiyi","sequence":"first","affiliation":[{"name":"Department of Crop Protection, Faculty of Agriculture, University of Ilorin, Ilorin 240003, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4738-7276","authenticated-orcid":false,"given":"Ayorinde Victor","family":"Ogundele","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Basicas, Facultad de Medicina, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9626-012X","authenticated-orcid":false,"given":"Sulyman Olalekan","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Industrial Chemistry, Faculty of Physical Sciences, University of Ilorin, Ilorin 240003, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0097-3761","authenticated-orcid":false,"given":"Hassan","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Federal University of Lafia, Lafia 950101, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7163-2123","authenticated-orcid":false,"given":"H\u00e9ctor Hern\u00e1n","family":"Silva","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias Basicas, Facultad de Medicina, Universidad de La Frontera, Temuco 4780000, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e70038","DOI":"10.1002\/gps.70038","article-title":"Prevention is better than cure: Public understanding of preventing neurodegenerative disorders","volume":"40","author":"Thomson","year":"2025","journal-title":"Int. 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