{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:02:18Z","timestamp":1779778938778,"version":"3.53.1"},"reference-count":169,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Neuroinflammation is a fundamental pathological hallmark driving the initiation and progression of various neurological disorders. Luteolin, a natural flavonoid abundant in medicinal plants, fruits, and vegetables, exerts multifaceted neuroprotective effects across diverse experimental disease models. Its beneficial activities are mediated through complementary mechanisms, including suppression of aberrant microglial activation, modulation of pro-inflammatory signaling pathways, and enhancement of endogenous antioxidant defenses. These integrated actions attenuate inflammatory mediator release, reduce oxidative stress-induced neuronal damage, and inhibit apoptosis, thereby counteracting neuroinflammation-driven pathology. This review synthesizes current knowledge on luteolin\u2019s protective roles in central nervous system (CNS) disorders. It elucidates underlying molecular mechanisms, encompassing regulation of key signaling cascades such as NF-\u03baB, MAPK, and Nrf2, as well as its impact on cellular processes including autophagy and mitochondrial function. Critical challenges hindering clinical translation\u2014notably limited oral bioavailability and restricted blood-brain barrier (BBB) permeability\u2014are systematically discussed to guide future research. A comprehensive understanding of luteolin\u2019s pleiotropic pharmacological actions will not only enhance knowledge of its therapeutic potential but may also facilitate the development of novel preventive and therapeutic strategies for neuroinflammatory and neurodegenerative diseases.<\/jats:p>","DOI":"10.3389\/fphar.2026.1844585","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:02:54Z","timestamp":1779775374000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Luteolin and neuroinflammation: a multi-target therapeutic strategy for central nervous system disorders"],"prefix":"10.3389","volume":"17","author":[{"given":"Jianting","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Yu","sequence":"additional","affiliation":[{"name":"Radiology Department, Qingdao Central Hospital, University of Health and Rehabilitation Sciences","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zou","sequence":"additional","affiliation":[{"name":"Qingdao Mental Health Center","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lezhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyi","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Rong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University","place":["Qingdao, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.3390\/pharmaceutics14051003","article-title":"Novel luteolin-loaded chitosan decorated nanoparticles for brain-targeting delivery in a sporadic Alzheimer's disease mouse model: focus on antioxidant, anti-inflammatory, and amyloidogenic pathways","volume":"14","author":"Abbas","year":"2022","journal-title":"Pharmaceutics"},{"key":"B2","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1177\/18796397251330144","article-title":"Emerging roles of microglia and neuroinflammation in Huntington's disease: from pathophysiology to clinical trials","volume":"14","author":"Abedrabbo","year":"2025","journal-title":"J. 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