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

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.