Protective effects of ginsenosides in cerebral small vessel disease: Cellular and molecular mechanisms

Cerebral small vessel disease (CSVD), an age-related vascular disorder linked to cognitive decline, lacks targeted therapies. Ginsenosides, bioactive compounds in ginseng, demonstrate multi-target potential against CSVD by modulating neurovascular dysfunction. Experimental studies highlight their anti-inflammatory, antioxidant, and neuroprotective properties. Ginsenosides suppress pro-inflammatory cytokines (tumor necrosis factor α [TNF-α], interleukin-1β [IL-1β], IL-6) via nuclear factor-kappa B/nod-like receptor protein (NF-κB/NLRP1) inflammasome inhibition, stabilize the blood-brain barrier by preserving tight junctions and reducing matrix metalloproteinase activity, and enhance endothelial survival through vascular endothelial growth factor/sonic hedgehog (VEGF/Shh)-mediated angiogenesis. They mitigate vascular remodeling by blocking vascular smooth muscle cell (VSMC) proliferation via phosphatidylinositol 3 kinase/protein kinase B (PI3K/Akt) and mitogen-activated protein kinase (MAPK) signaling, while attenuating microglial activation and astrocyte dysfunction to improve cerebral blood flow. These compounds also alleviate oxidative stress and promote neurovascular unit integrity. Future research should focus on optimizing ginsenoside combinations, elucidating protein interactions, and exploring synergies with complementary agents to enhance therapeutic efficacy. Ginsenosides represent a promising multi-mechanistic approach for CSVD treatment, addressing inflammation, vascular pathology, and neural damage.