A 4.7-kDa polysaccharide from Panax ginseng suppresses Aβ pathology via mitophagy activation in cross-species Alzheimer's disease models.

Alzheimer's disease (AD) is a neurological condition that progresses with age. Amyloid-β (Aβ) aggregation has been suggested to be a key pathogenic process in Alzheimer's disease. Ginseng polysaccharides (GP), the main biologically active components isolated from Panax ginseng C. A. Meyer (ginseng), may act as neuroprotective agents with potential benefits for AD patients. However, GP effects on Aβ pathology and AD symptoms are still unclear. Here, a 4.7-kDa GP termed GP4 was purified and subjected to basic physicochemical characterization. The biological effects of GP4 to prevent Aβ aggregation were then assessed with cross-species AD models, including Aftin-5-treated SH-SY5Y cells and cerebral organoids, and transgenic C. elegans overexpressing the full-length human Aβ 42 peptide. These analyses ultimately demonstrated that GP4 was capable of inhibiting Aβ accumulation both in vivo and vitro , and with early intervention of GP4 being sufficient to alleviate Aβ 42 -associated aging phenotypes and memory loss in C. elegans model of AD. Furthermore, neuroinflammation was significantly down-regulated in human cells and cerebral organoids. From a mechanistic perspective, the ability of GP4 to inhibit Aβ aggregation was found to be related to its ability to promote neuronal mitophagic activity. This finding offers a robust theoretical foundation for the further development of GP4 as a candidate drugs with the potential to treat AD. [Display omitted] • A 4.7-kDa ginseng polysaccharides termed GP4 was purified from Panax ginseng and subjected to basic physicochemical characterization using HPGPC, HPLC, FT-IR and NMR analyses. • GP4 was capable of inhibiting Aβ accumulation in cross-species AD models, including Aftin-5-treated SH-SY5Y cells and cerebral organoids, and transgenic C. elegans overexpressing the full-length human Aβ 42 peptide. • Early intervention of GP4 being sufficient to alleviate Aβ 42 -associated aging phenotypes and memory loss in vivo. • Neuroinflammation was significantly down-regulated in vitro models of AD. • GP4 repressed Aβ accumulation via promoting neuronal mitophagic activity. [ABSTRACT FROM AUTHOR]