Alzheimer's disease (AD) incidence is rising with no effective treatments. Eleutheroside B (EB) has neuroprotective potential, but its therapeutic effects and mechanisms in AD are unclear. This study investigated EB's effects on AD pathologies and elucidated its underlying mechanisms using a transgenic Caenorhabditis elegans ( C. elegans ) model. We found that EB could ameliorate cognitive impairment, locomotor dysfunction, and shortened lifespan induced by amyloid-β(Aβ) and Tau aggregation in C. elegans , and reduce the relative expression levels of Aβ, Tau, and phosphorylated Tau (p-Tau) proteins. EB significantly improved the health status and anti-aging capacity of the worms, as evidenced by prolonged healthspan, elevated pharyngeal pumping rate and body bend frequency, and increased body length and width. Notably, EB exhibited no observable toxicity even at high-dose administration. Furthermore, EB activated key antioxidant transcription factors skn-1 , daf-16 , and hsf-1 ; it also increased the expression levels of antioxidant enzymes superoxide dismutase-3(SOD-3) and glutathione S-transferase 4(GST-4), decreased reactive oxygen species (ROS) levels, and elevated the expression of heat shock proteins Hsp-4 and Hsp-6. EB also reduced the accumulation of p62/SQST-1 protein, promoted the colocalization of lgg-1::GFP with lysosomes, and increased the relative mRNA expression of autophagy-related genes aak-2 , unc-51 , bec-1 , vps-34 , and lgg-1 . After targeted knockdown of these genes, the protective effects of EB against AD-related pathologies were abolished. Our findings demonstrate that EB exhibits anti-aging properties and potential for ameliorating AD, which is likely mediated via antioxidative activities and autophagy induction.
Regulating microglia to modulate the inflammatory response in the early stages of spinal cord injury is crucial for neural repair. Commonly used drugs to inhibit inflammation and microglial activity in clinical practice, such as glucocorticoids and immunosuppressants, are associated with potential side effects. Eleutheroside B (EB), a natural plant extract, has been demonstrated an efficient anti-inflammatory action with low toxicity and the ability to promote neural repair and axon regeneration, suggesting its potential role in treating SCI. Recently, magnetically driven microrobots have demonstrated the ability to deliver drugs and provide precise targeting in deep tissues, which may help increase the dose of EB at the injury site. In this study, we design biomimetic magnetically driven microrobots loaded with EB, which offer efficient motion control and drug delivery capabilities. In a mouse SCI model, the magnetic microrobot with macrophage membrane functionalized and EBs (MPE robot) actively target the injured area using rotating magnetic fields in the early stages of injury, modulated the local microglial phenotype to a neuroprotective state, inhibited local inflammation, and promote axon regeneration and neurological recovery. This approach demonstrates that a biomimetic microrobot loaded with EB offers an effective strategy for treating SCI and other central nervous system diseases.
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