Mechanism of Black American Ginseng Saponins in Ameliorating Memory Dysfunction in Aging Mice by Activating the BDNF/PI3K/AKT/CREB Pathway.

Abstract

Black American Ginseng (Panax quinquefolium L.) is a traditional Chinese medicine taken orally. While saponins from American Ginseng are known to enhance memory, the effects and mechanisms of Black American Ginseng saponins remain unclear. This study investigates their potential in alleviating memory impairment in aging mice. UPLC-Q-Orbitrap-MS/MS was used to identify compounds in Black American Ginseng, and network pharmacology predicted potential targets. The Morris water maze test assessed cognitive function, while Western blot and ELISA measured BDNF, TrkB, inflammatory markers (IL-1β, TNF-α, IL-6), and the activation of the PI3K/AKT/CREB signaling pathway. Networking pharmacology and PPI analysis identified PIK3CA, EGFR, and PIK3R1 as key targets, with KEGG enrichment highlighting the PI3K/AKT pathway. Behavioral tests confirmed that Black American Ginseng saponins significantly improved memory in aging mice. Molecular analyses revealed upregulation of BDNF and TrkB and suppression of IL-1β and IL-6. Additionally, Western blot confirmed activation of the PI3K/AKT/CREB pathway, supporting its neuroprotective role. Black American Ginseng saponins enhance cognitive function by modulating neurotrophic signaling and reducing neuroinflammation. These findings provide new insights into their potential therapeutic application for age-related cognitive decline.