Schisandrin B loaded carrier with synergistic antioxidation alleviates Alzheimer’s disease in Caenorhabditis elegans by prolonging lifespan and inhibiting Aβ aggregation

Oxidative stress and amyloid- β ( Aβ ) deposition are closely linked to the occurrence and progression of Alzheimer’s disease (AD). Herein, a strategy for alleviating AD by simultaneously inhibiting Aβ aggregation and scavenging excess ROS was proposed. An antioxidant amphiphilic polymer, DSe-Cys-(PEG) 2 , containing diselenide linkages was synthesized to load hydrophilic Schisandrin B (Sch B), which has antioxidant and heat shock response-promoting properties. DSe-Cys-(PEG) 2 self-assembled with Sch B to form nanosized M@Sch B micelles, demonstrating significant scavenging effects on H 2 O 2 , Fe 3+ , ·DPPH, ·ABTS + , and improvement the aging-related phenotypes in Caenorhabditis elegans ( C. elegans ) CL4176, including a 33.33% increase in maximum lifespan, a 51.08% enhancement in locomotion ability, a 38.10% rise in body bending frequency, delayed egg-laying, and paralysis prevention compared to the control group. Furthermore, M@Sch B significantly retarded aging by reducing lipofuscin accumulation and decreasing ROS accumulation by enhancing antioxidases activity and reducing malondialdehyde content. M@Sch B upregulated the expression of anti-aging genes daf-16 , antioxidant stress genes ( skn-1 , sod-3 ), and key heat shock factors ( hsf-1 , hsp-16.2 ), while downregulating aging genes ( daf-2 , age-1 ) and Aβ mRNA expression based on the synergistic antioxidant effect of M and Sch B. M@Sch B can simultaneously mitigates multiple AD-related factors, including synergistic antioxidant effects and inhibition of Aβ aggregation, which are of great significance for delaying aging and treating AD.