Ginseng extract improves synaptic resiliency: A key factor for healthy cognitive aging

Abstract INTRODUCTION Disruption of the autophagy‐lysosomal pathway (ALP) compromises proteostasis and contributes to aging‐related proteinopathy. Many studies indicate that a healthy diet can improve cognitive health and reduce the risk of Alzheimer‐type pathogenesis. METHODS Plant‐based products were tested in hippocampal explants for amplifying the ALP component cathepsin B (CatB), a protease reported to reduce proteinopathy and synaptopathy. Proof‐of‐concept experiments also tested Panax quinquefolius extract (PanQ) for improving cognitive function in aging rats. RESULTS Among the natural extracts tested, PanQ emerged as the most effective for increasing the active CatB isoform in correspondence with enhanced levels of synaptic proteins and the autophagy marker LC3‐II. PanQ also increased synaptic resilience in a model of lysosomal stress and improved cognitive performance in 20‐month‐old rats. DISCUSSION PanQ‐mediated ALP enhancement implicates the proteostasis network in synaptic and cognitive maintenance mechanisms. This study also points to synaptic resiliency as an important factor underlying the influence of dietary components on cognitive health. Highlights Panax quinquefolius (PanQ) enhanced cathepsin B (CatB) in hippocampal explants. The CatB modulation corresponded with enhanced synaptic and autophagy markers. PanQ improved synaptic resilience in the chloroquine (Cqn) model of lysosomal stress. Age‐related cognitive deficit was reduced by PanQ supplementation in Fischer rats.