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This study proposes a \u201cmulti\u2010target synergy and dose threshold control\u201d exploratory framework for evaluating\n                    <jats:italic>Idesia polycarpa<\/jats:italic>\n                    crude oil (IPCO) in an aluminum\u2010induced AD model. An integrated analytical approach employing GC\u2013MS and network pharmacology was used to identify three candidate core components\u2014(Z,Z)\u20109,12\u2010octadecadienoic acid, Beta\u2010amyrin, and 2,4\u2010di\u2010tert\u2010butylphenol\u2014that were computationally predicted to influence a network of 35\u2009\n                    <jats:sc>ad<\/jats:sc>\n                    \u2010related pathways (e.g., Calcium and PPAR signaling) via eight potential key targets (including\n                    <jats:italic>PTGS2<\/jats:italic>\n                    ,\n                    <jats:italic>PPARG<\/jats:italic>\n                    , and\n                    <jats:italic>AKT1<\/jats:italic>\n                    ). In\u00a0vivo experiments revealed a dose\u2010dependent modulation of AD\u2010related pathology following IPCO intervention. The high\u2010dose group showed the most marked improvements in several therapeutic markers, including reduced aluminum load, an anti\u2010inflammatory shift in cytokine levels (elevated IL\u201010, decreased IL\u20104, IL\u20106, IL\u20101\u03b2, and TNF\u2010\u03b1), and remodeling of the gut microbiota characterized by an increase in putative short\u2010chain fatty acid (SCFA)\u2010producing genera such as the\n                    <jats:italic>[Eubacterium]\u2010xylanophilum\u2010group<\/jats:italic>\n                    and\n                    <jats:italic>NK4A214\u2010group<\/jats:italic>\n                    (\n                    <jats:italic>Firmicutes<\/jats:italic>\n                    ). Paradoxically, this same high dose was associated with a decline in spatial cognitive performance. This biphasic effect may be preliminarily explained by a dual microbial mechanism: the inhibition of the pro\u2010inflammatory associated\n                    <jats:italic>[Eubacterium]\u2010oxidoreducens\u2010group<\/jats:italic>\n                    alongside the expansion of taxa linked to a neuroprotective SCFA metabolic network. As one of the first studies to map these multi\u2010dimensional \u201cconstituent\u2013microbiota\u2013neuroinflammation\u201d interactions for IPCO, our findings highlight its complex, dose\u2010sensitive bioactivity. Importantly, they underscore the critical need for subsequent pharmacokinetic and direct target engagement studies.\n                  <\/jats:p>","DOI":"10.1002\/fsn3.71702","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T11:40:28Z","timestamp":1776685228000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated Network Pharmacology, Molecular Docking, and Experimental Validation Elucidating the Therapeutic Mechanism of\n                    <i>Idesia polycarpa<\/i>\n                    Crude Oil in Aluminum Chloride\u2010Induced Alzheimer's Rat Models"],"prefix":"10.1002","volume":"14","author":[{"given":"Weijie","family":"Chang","sequence":"first","affiliation":[{"name":"College of Biological and Food Engineering Hubei Minzu University  Enshi Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaobing","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Biological and Food Engineering Hubei Minzu University  Enshi Hubei China"},{"name":"Hubei Key Laboratory of Biologic Resources Protection and Utilization Hubei Minzu University  Enshi Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianquan","family":"Kan","sequence":"additional","affiliation":[{"name":"College of Food Science Southwest University  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiufang","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Biological and Food Engineering Hubei Minzu University  Enshi Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4345-4868","authenticated-orcid":false,"given":"Kai","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Biological and Food Engineering Hubei Minzu University  Enshi Hubei China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1208494109"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn2648"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0039-1678581"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-024-01169-4"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2022.101619"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0434-1"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222111556"},{"key":"e_1_2_12_9_1","first-page":"CD001190","article-title":"Donepezil for Dementia Due to Alzheimer's Disease","volume":"6","author":"Birks J. 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