Lycium barbarum Polysaccharide Alleviates Amyloid‐β‐Induced Toxicity in the Caenorhabditis elegans Model

Abstract

ABSTRACTAlzheimer's disease (AD) poses a significant global health challenge, primarily characterized by the aggregation of β‐amyloid (Aβ) peptides and associated oxidative stress. Given the lack of effective AD drugs, we investigated the effects of Lycium barbarum polysaccharide (LBP), a water‐soluble polysaccharide from goji berries, on Aβ scavenging, aggregation, and Aβ‐induced toxicity using the transgenic AD nematode. LBP treatment delayed paralysis, mitigated Aβ‐induced chemotaxis deficits, and reduced Aβ1–42 deposition and oligomer formation in AD nematodes. Furthermore, LBP supplementation alleviated Aβ‐induced oxidative stress and improved oxidative stress resistance through the insulin/insulin growth factor 1 (IGF‐1) signaling (IIS) pathway. Evaluation of the Aβ clearance pathway revealed that LBP attenuated Aβ toxicity by increasing proteasome activity rather than lysosomal levels. Basic physiological assessments further indicated that LBP was non‐toxic in vivo and promoted nematode health. Our findings suggest that LBP ameliorates AD‐like symptoms in nematodes by activating the IIS pathway to reduce oxidative stress and enhancing proteasomal activity to clear Aβ aggregates, providing a new theoretical basis for considering LBP as a promising therapeutic drug for AD and related oxidative stress complications.