Semen Ziziphi Spinosae (SZS) demonstrates neuroprotective effects by attenuating lipopolysaccharide (LPS)-induced blood-brain barrier (BBB) dysfunction. Proteomic analysis revealed that SZS significantly altered 135 proteins in rat brains, primarily affecting cell-cell adhesion and adherens junctions. SZS reversed LPS-induced BBB breakdown by activating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway. Molecular docking studies indicated that SZS components, such as 6''-feruloylspinosin, spinosin, and swertisin, strongly bind to signaling pathway proteins. These findings suggest SZS's potential in preventing cerebral diseases and its further application as a functional food.
