Available online 6 October 2025

Chronic cerebral hypoperfusion (CCH) is a major risk factor for vascular cognitive impairment (VCI). Angiogenesis plays a critical role in recovery from cerebrovascular disease. Panaxadiol (PD), a key active component of ginseng, exhibits neuroprotective effects; however, its role in promoting angiogenesis post-CCH remains unclear.

A bilateral common carotid artery stenosis (BCAS) model was used to investigate the effects of PD (50 mg/kg, 30 days) on cerebral blood flow (CBF), cognitive function, and angiogenesis in mice. Cognitive tests included the Morris water maze (MWM), novel object recognition (NOR), and Y-maze. Vascular changes were assessed using laser speckle imaging and immunofluorescence. The effects of PD on endothelial cell (EC) functions were evaluated in vitro using bEnd.3 cells. Potential mechanisms were examined through protein chip analysis, protein-protein interaction (PPI) network analysis, molecular docking techniques, and in vitro experimental validation.

PD increased CBF and alleviated cognitive impairment in BCAS mice. It enhanced neovascularization in the hippocampus and promoted EC proliferation, migration, and tube formation in vitro. Mechanistically, PD activated the vascular endothelial growth factor A (VEGF-A) and p38 mitogen-activated protein kinase (p38 MAPK) pathway while inhibited steroid receptor coactivator (Src) activity.

PD ameliorates BCAS-induced cognitive deficits by promoting angiogenesis through the VEGF-A/p38 MAPK/Src signaling pathway, highlighting its potential as a therapeutic agent for CCH and VCI.

Ginseng

chronic cerebral hypoperfusion

panaxadiol

angiogenesis

VEGF-A

© 2025 The Korean Society of Ginseng. Publishing services by Elsevier B.V.