Glycoside components promote endothelial progenitor cell-derived exosomes repairing damaged vascular endothelium via the PI3K/AKT signaling pathway.

OBJECTIVE

This paper investigated the effects of three glycosides-astragaloside IV, amygdalin, and paeoniflorin (AAP)-derived from Buyang Huanwu Decoction combined with endothelial progenitor cell-derived exosomes (EPC-Exo), on vascular endothelial repair in rats following balloon-induced injury, with specific focus on the PI3K/AKT signaling pathway.

METHODS

Endothelial progenitor cells (EPC) were isolated, cultured, and identified using immunofluorescence, with EPC-Exo being validated through Western blotting (WB), transmission electron microscopy, and particle size analysis. A rat model of endothelial injury was established using a HFD and carotid artery balloon injury (CABI). The rats were subsequently treated with AAP and/or EPC-Exo. Vascular repair was evaluated using hematoxylin-eosin (H&E) staining, ELISA, immunofluorescence, and WB. In vitro, endothelial cell injury was induced, and treatment effects were analyzed using CCK-8, scratch assays, tube formation assays, immunofluorescence, and WB. The involvement of the PI3K/AKT pathway was verified using the PI3K inhibitor LY294002.

RESULTS

The combination of AAP and EPC-Exo significantly reduced intimal hyperplasia, improved endothelial function, and promoted angiogenesis. Network pharmacology and molecular docking analyses demonstrated strong interactions between AAP and PI3K/AKT-related proteins. By enhancing the uptake of EPC-Exo by vascular endothelial cells (VEC), AAP promoted proliferation, migration, and tube formation in vitro while reducing Cleaved-caspase 3 expression. This combination also increased activation of the PI3K/AKT signaling pathway. The PI3K inhibitor weakened these effects, verifying the pathway's involvement in vascular repair.

CONCLUSION

The combination of AAP and EPC-Exo synergistically promotes vascular endothelial repair and angiogenesis, partly by enhancing EPC-Exo uptake through activation of the PI3K/AKT signaling pathway.