A Neutral Polysaccharide from Ginseng Berry Mitigates D-Galactose-Induced Oxidative Stress and Cognitive Deficits Through the Keap1/Nrf2/HO-1/NQO1 Pathway

Oxidative stress contributes to brain aging processes and is implicated in related functional decline. Developing strategies to mitigate oxidative stress is therefore of significant interest. In this study, a neutral polysaccharide (GBPN) was isolated from ginseng berry. Structural analysis revealed that GBPN (molecular weight 1.52 × 10⁴ Da) is primarily composed of glucose (53.18%), arabinose (24.3%), and galactose (16.75%). Glucose exists in the forms of →4)-Glc<i>p</i>-(1→ (32.95%), →6)-Glc<i>p</i>-(1→ (13.81%), and →4,6)-Glc<i>p-</i>(1→ (3.70%), while arabinose exists as →1)-Ara<i>f</i> (9.73%), →1)-Ara<i>p</i> (5.82%), →2)-Ara<i>p</i>-(1→ (0.66%), →5)-Ara<i>f</i>-(1→ (7.62%), and →3,5)-Ara<i>f</i>-(1→ (1.69%) forms, while galactose exists in the forms of →1)-Gal<i>p</i> (3.58%), →3)-Gal<i>p</i>-(1→ (1.59%), and →3,6)-Gal<i>p</i>-(1→ (12.67%). GBPN adopts a triple-helix conformation and exhibits a curled lamellar appearance. Functionally, GBPN exhibited strong 2,2-diphenyl-1-picrylhydrazyl radical, hydroxyl radical scavenging activity, and iron ion chelation capacity. It can activate the antioxidant system in D-galactose-induced aging-like mice, and simultaneously enhance their learning and memory abilities. Mechanistic analysis revealed that these effects are associated with the kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 pathway. These findings suggest that ginseng berry polysaccharides like GBPN hold promise as potential agents for alleviating oxidative stress and cognitive deficits in aging-related contexts.