Study on the mechanism of Xanthoceras sorbifolia Bunge oil in the treatment of Alzheimer's disease by an integrated "network pharmacology-metabolomics" strategy.

Xanthoceras sorbifolia Bunge oil (XSBO) has garnered significant interest from researchers due to its distinctive anti-Alzheimer's disease (AD) properties. However, the underlying molecular mechanism remain unclear. This study aims to investigate the potential mechanisms by which XSBO may exert therapeutic effects on AD by employing a combination of network pharmacology analysis and experimental validation. The chemical composition and absorbed compounds of XSBO were identified using GC-MS and LC-MS. Network pharmacology analysis was performed using various computational tools to identify hub genes and construct compound-target-pathway networks. Subsequently, both in vitro and in vivo experiments were conducted to confirm the mechanisms by which XSBO may treat AD. The results identified 43 active compounds in XSBO, targeting a total of 223 genes, of which 191 were associated with AD. Network analysis indicated that the active constituents in XSBO, such as 9,12-octadecadienoic acid, linoelaidic acid and 11-octadecenoic acid, interact with targets including MAPK1, MAPK3, AKT1, RXRA, RXRB, PPARD and PPARA to modulate inflammation-related signalling pathways and the sphingolipid signalling pathway. In vitro investigations corroborated that XSBO can significantly influence the viability of Aβ25-35-induced SH-SY5Y cells via the MAPK pathway. This study demonstrated that XSBO has the potential to mitigate inflammation network disorders through the MAPK pathway and to restore sphingolipid metabolite levels in AD rats, thereby laying a groundwork for future studies.