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Kai\u2010Xin\u2010San (KXS), with definite curative effects, is widely used for the prevention and treatment of <jats:sc>AD<\/jats:sc> in China. But its mechanism is not yet fully understood. Based on our established rat model and previous pharmacodynamics study, Multi\u2010omics (metabolomics, proteomics) and network analysis were integrated to explore the holistic mechanism of anti\u2010<jats:sc>AD<\/jats:sc> effects of KXS. The key pathways were validated with western blot and ELISA methods. Morris water maze and Nissl staining showed that KXS could ameliorate cognitive deficits and pathological morphology of the hippocampus in <jats:sc>AD<\/jats:sc> rats. A total of nine metabolites were identified, which were related to pyrimidine metabolism, riboflavin metabolism, tyrosine metabolism, tryptophan metabolism, and glycerophospholipid metabolism. Proteomics results indicated that the improvement of cognitive deficits by KXS was closely related to the regulation of oxidative phosphorylation in mitochondria. Western blotting results showed that KXS significantly inhibited the expression of Mt\u2010nd2 and Ndufb6 in <jats:sc>AD<\/jats:sc> rats. Integrated analysis indicated that the anti\u2010<jats:sc>AD<\/jats:sc> targets of KXS were interrelated and KXS could exert its anti\u2010<jats:sc>AD<\/jats:sc> effect by reducing oxidative stress, neurotoxicity, and inflammation.<\/jats:p>","DOI":"10.1002\/bmc.70047","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T06:44:04Z","timestamp":1741070644000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploring the Mechanism of Kai\u2010Xin\u2010San to Improve Cognitive Deficits in <scp>AD<\/scp> Rats Induced by D\u2010Gal and A\u03b2<sub>25\u201335<\/sub> Based on Multi\u2010Omics and Network Analysis"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7197-8067","authenticated-orcid":false,"given":"Lifen","family":"Zhou","sequence":"first","affiliation":[{"name":"Key Laboratory of Modern Preparation of TCM, Ministry of Education Jiangxi 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