Protective Potentials of Natural Products Against Vascular Dementia: A Comprehensive Review of Experimental Studies

Vascular dementia (VaD), accounting for up to 20% of dementia cases globally, is primarily driven by chronic cerebral hypoperfusion (CCH), which leads to progressive cognitive impairment. Despite the increasing prevalence of VaD, effective treatments remain limited. Natural products-including herbal formulas, single herbs, and phytochemicals-have emerged as promising candidates due to their multi-targeted biological activities. This review aimed to evaluate the efficacy and underlying mechanisms of natural products in ameliorating CCH-induced VaD in experimental rodent models, and to identify feasible mechanistic pathways and targets. Protective effects of natural products were mediated by enhanced vascular regeneration, BBB stability, synaptic plasticity, and neurotrophic signaling along with reduced oxidative stress, neuroinflammation, and apoptosis. Among the proteins concerned, the serine/threonine kinase Akt1 emerged as a primary regulatory protein involved in coordinating survival and inflammatory responses. Predominantly male rat models were subjected to bilateral common carotid artery occlusion (BCCAo) or bilateral common carotid artery stenosis (BCAS) to mimic clinical features of CCH. These two models provided a robust and translational strategy for a preclinical approach against VaD. The interconnected network analysis facilitated the discovery of core anti-VaD interventions by linking established herbal formulas with promising, yet understudied, botanical resources. Natural products demonstrate multitargeted protective potential in VaD animal models by targeting multiple pathological processes. Further investigation of underexplored herbs and phytochemicals may expand treatment strategies and support the development of novel and multi-targeted interventions for VaD.