Systematically Characterize the Anti-Alzheimer’s Disease Mechanism of Lignans from S. chinensis Based on In-Vivo Ingredient Analysis and Target-Network Pharmacology Strategy by UHPLC–Q-TOF-MS

Lignans fromSchisandra chinensis(Turcz.) Baill can ameliorate cognitive impairment in animals with Alzheimer’s disease (AD). However, the metabolism of absorbed ingredients and the potential targets of the lignans fromS. chinensisin animals with AD have not been systematically investigated. Therefore, for the first time, we performed an in-vivo ingredient analysis and implemented a target-network pharmacology strategy to assess the effects of lignans fromS. chinensisin rats with AD. Ten absorbed prototype constituents and 39 metabolites were identified or tentatively characterized in the plasma of dosed rats with AD using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. Based on the results of analysis of the effective constituents in vivo, the potential therapeutic mechanism of the effective constituents in the rats with AD was investigated using a target-network pharmacology approach and independent experimental validation. The results showed that the treatment effects of lignans fromS. chinensison cognitive impairment might involve the regulation of amyloid precursor protein metabolism, neurofibrillary tangles, neurotransmitter metabolism, inflammatory response, and antioxidant system. Overall, we identified the effective components of lignans inS. chinensisthat can improve the cognitive impairment induced by AD and proposed potential therapeutic metabolic pathways. The results might serve as the basis for a fundamental strategy to explore effective therapeutic drugs to treat AD.Keywords:Alzheimer’s disease;lignan;metabolite identification;Schisandra chinensis;target-network pharmacology;UHPLC–Q-TOF-MS