Semen Ziziphi Spinosae attenuates blood-brain barrier dysfunction induced by lipopolysaccharide by targeting the FAK-DOCK180-Rac1-WAVE2-Arp3 signaling pathway

Semen Ziziphi Spinosae (SZS) has been extensively used in the daily diet as a functional food for neuroprotective health-benefit in China for many years. However, the neuroprotective mechanism of SZS associated with blood-brain barrier (BBB) integrity remains unexplored. The present study suggests SZS could protect against lipopolysaccharide (LPS)-induced BBB dysfunction. Proteomics indicate that 135 proteins in rat brain are significantly altered by SZS. These differentially expressed proteins are mainly clustered into cell-cell adhesion and adherens junctions, which are closely related with BBB integrity. SZS reversed LPS-induces BBB breakdown by activating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway. Molecular docking between signaling pathway proteins and identified SZS components in rat plasma reveals that 6'-feruloylspinosin, spinosin, and swertisin strongly binds to signaling proteins at multiple amino acid sites. These novel findings suggest a health benefit of SZS in prevention of cerebral diseases and contributes to the further application of SZS as a functional food.

Automated summary

This research demonstrates the neuroprotective effect of Semen Ziziphi Spinosae (SZS) against lipopolysaccharide-induced blood-brain barrier dysfunction. Proteomic analysis reveals that SZS alters the expression of proteins related to cell-cell adhesion and adherens junctions. The study also identifies a specific signaling pathway through which SZS protects the blood-brain barrier integrity. Molecular docking analysis suggests that certain components of SZS bind strongly to signaling proteins. These findings contribute to the understanding of SZS as a functional food for preventing cerebral diseases.