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Aging Neurosci."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Oxidative stress, cholinergic deficiency, and neuroinflammation are hallmarks of most neurodegenerative disorders (NDs). Lipids play an important role in brain development and proper functioning. Marine-derived lipids have shown good memory-improving potentials, especially those from fish and microalgae. The cultivated macroalga <jats:italic>Hizikia fusiforme<\/jats:italic> is healthy food and shows benefits to memory, but the study is rare on the brain healthy value of its oil. Previously, we had reported that the <jats:italic>Hizikia fusiforme<\/jats:italic> functional oil (HFFO) contains arachidonic acid, 11,14,17-eicosatrienoic acid, phytol, and other molecules displaying <jats:italic>in vitro<\/jats:italic> acetylcholinesterase inhibitory and nitroxide scavenging activity; however, the <jats:italic>in vivo<\/jats:italic> effect remains unclear. In this study, we further investigated its potential effects against lipopolysaccharides (LPS)- or aluminum trichloride (AlCl<jats:sub>3<\/jats:sub>)-induced memory deficiency in zebrafish and its drug-related properties <jats:italic>in silica<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established memory deficit models in zebrafish by intraperitoneal (i.p.) injection of lipopolysaccharides (LPS) (75 ng) or aluminum trichloride (AlCl<jats:sub>3<\/jats:sub>) (21 \u03bcg), and assessed their behaviors in the T-maze test. The interleukin-1\u03b2 (IL-1\u03b2), tumor necrosis factor-\u03b1 (TNF-\u03b1), acetylcholine (ACh), and malondialdehyde (MDA) levels were measured 24 h after the LPS\/AlCl<jats:sub>3<\/jats:sub> injection as markers of inflammation, cholinergic activity, and oxidative stress. Furthermore, the interaction of two main components, 11,14,17-eicosatrienoic acid and phytol, was investigated by molecular docking, with the important anti-inflammatory targets nuclear factor kappa B (NF-\u03baB) and cyclooxygenase 2 (COX-2). Specifically, the absorption, distribution, metabolism, excretion, and toxicity (ADMET) and drug-likeness properties of HFFO were studied by ADMETlab.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results showed that HFFO reduced cognitive deficits in zebrafish T-maze induced by LPS\/AlCl<jats:sub>3<\/jats:sub>. While the LPS\/AlCl<jats:sub>3<\/jats:sub> treatment increased MDA content, lowered ACh levels in the zebrafish brain, and elevated levels of central and peripheral proinflammatory cytokines, these effects were reversed by 100 mg\/kg HFFO except for MDA. Moreover, 11,14,17-eicosatrienoic acid and phytol showed a good affinity with NF-\u03baB, COX-2, and HFFO exhibited acceptable drug-likeness and ADMET profiles in general.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Collectively, this study's findings suggest HFFO as a potent neuroprotectant, potentially valuable for the prevention of memory impairment caused by cholinergic deficiency and neuroinflammation.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2022.941994","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T05:21:15Z","timestamp":1662700875000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Hizikia fusiforme functional oil (HFFO) prevents neuroinflammation and memory deficits evoked by lipopolysaccharide\/aluminum trichloride in zebrafish"],"prefix":"10.3389","volume":"14","author":[{"given":"Ying-Ying","family":"Nie","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Long-Jian","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-Mei","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Cong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Yue","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-You","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Xiang","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong-Ping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng-Zhi","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1007\/s12640-019-9999-2","article-title":"Asiatic acid attenuated aluminum chloride-induced tau pathology, oxidative stress and apoptosis via AKT\/GSK-3\u03b2 signaling pathway in wistar rats","volume":"35","author":"Ahmad Rather","year":"2019","journal-title":"Neurotoxic. 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