Multitarget Protective Effects of JUB on Aβ-Induced Neurotoxicity and the Mechanism Predication Using Network Pharmacology Analysis

Amyloid-β (Aβ) is one of the core factors in the pathogenesis of Alzheimer’s disease (AD), and the accumulation of its aggregates in the brain can form age-related plaques, leading to brain cell damage and intellectual decline, which may be the common intersection of all causes of neurotoxicity. Jujuboside B (JUB) has many characteristics such as hypnosis, sedation, antianxiety, and antioxidant stress. However, it is still unclear whether JuB can alleviate the neurotoxicity caused by Aβ. Our study demonstrates that JUB improves learning and memory deficits in the nematode model. At the same time, JUB increases the antioxidant activity, prevents excessive accumulation of lipid synthesis, and resists endogenous lipofuscin deposition, thereby inhibiting the toxic effect of Aβ. In vitro, JUB can improve Aβ1–42-induced neuronal apoptosis level through the Bax/Bcl-2/caspase-3 signaling pathway and restore mitochondrial function in SH-SY5Y cells. The network pharmacology has been used to predict the potential neuroprotective mechanism of JUB. In summary, JUB exhibits neuroprotective properties employing both a neural cell and a nematode, which provides a basis for screening candidate ingredients for preventing AD.