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It has anti\u2010oxidant and anti\u2010inflammatory activities and improves glucose metabolism by potentiating insulin sensitivity and improving \u03b2\u2010cell function and mass. Alzheimer's disease (AD) is induced by the deposition of amyloid\u2010beta (A\u03b2) in the hippocampus and the formation of neurotoxic A\u03b2 plaques. The A\u03b2 deposition is associated with increased formation of A\u03b2 from amyloid precursor protein by up\u2010regulation of \u03b2\u2010secretase and \u03b2\u2010site amyloid precursor protein\u2010cleaving enzyme 1 (BACE1). Furthermore, A\u03b2 accumulation is increased by brain insulin resistance. The impairment of insulin\/IGF\u20101 signaling mainly in the hippocampus and brain insulin resistance is connected to signals originating in the liver and gut microbiota, known as the gut microbiota\u2010liver\u2010brain axis. This indicates that the changes in the production of short\u2010chain fatty acids by the gut microbiota and pro\u2010inflammatory cytokines can alter insulin resistance in the liver and brain. Luteolin is detected in the brain tissues after passing through the blood\u2013brain barrier, where it can directly influence neuroinflammation and brain insulin resistance and modulate A\u03b2 deposition. Luteolin (10\u201370\u2009mg\/kg bw for rodents) can modulate the systemic and brain insulin resistance, and it suppresses AD development directly, and it influences A\u03b2 deposition by activation of the gut microbiota\u2010liver\u2010brain axis. In this review, we evaluate the potential of luteolin to mitigate two potential causes of AD, neuroinflammatory processes, and disruption of glucose metabolism in the brain. This review suggests that luteolin intake can enhance brain insulin resistance and neuroinflammation, directly and indirectly, to protect against the development of Alzheimer's\u2010like disease, and the gut microbiota\u2010liver\u2010brain axis is mainly involved in the indirect pathway. However, most studies have been conducted in animal studies, and human clinical trials are needed.<\/jats:p>","DOI":"10.1002\/biof.1703","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T09:21:55Z","timestamp":1608628915000},"page":"218-231","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":140,"title":["Protection against Alzheimer's disease by luteolin: Role of brain glucose regulation, anti\u2010inflammatory activity, and the gut microbiota\u2010liver\u2010brain axis"],"prefix":"10.1002","volume":"47","author":[{"given":"James W.","family":"Daily","sequence":"first","affiliation":[{"name":"Department of R&amp;D, Daily Manufacturing Inc  Rockwell North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suna","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition Obesity\/Diabetes Research Center, Hoseo University  Asan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6092-8340","authenticated-orcid":false,"given":"Sunmin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Food and Nutrition Obesity\/Diabetes Research Center, Hoseo University  Asan South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,21]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-019-0063-8"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(77)91780-9"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.31887\/DCNS.2000.2.2\/lschneider"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2013.08.007"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22030334"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1705971"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1706441"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2020.07.327"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2156-5"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/138955709787001712"},{"key":"e_1_2_13_12_1","volume-title":"IUPAC compendium of chemical terminology","author":"McNaught AD","year":"1997"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00692"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9030216"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800908786241050"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2018.81347"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom9110731"},{"key":"e_1_2_13_18_1","volume-title":"The handbook of natural flavonoids","author":"K.R. 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