Plantainoside B in Bacopa monniera Binds to Afl Aggregates Attenuating Neuronal Damage and Memory Deficits Induced by Afl

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by dementia. The most characteristic pathological changes in AD brain include extracellular amyloid-fl (Afl) accumulation and neuronal loss. Particularly, cholinergic neurons in the nucleus basalis of Meynert are some of the first neuro-nal groups to degenerate; accumulating evidence suggests that Afl oligomers are the primary form of neuro-toxicity. Bacopa monniera is a traditional Indian memory enhancer whose extract has shown neuroprotective and Afl-reducing effects. In this study, we explored the low molecular weight compounds from B. monniera extracts with an affinity to Afl aggregates, including its oligomers, using Afl oligomer-conjugated beads and identified plantainoside B. Plantainoside B exhibited evident neuroprotective effects by preventing Afl attach-ment on the cell surface of human induced pluripotent stem cell (hiPSC)-derived cholinergic neurons. More-over, it attenuated memory impairment in mice that received intrahippocampal Afl injections. Furthermore, radioisotope experiments revealed that plantainoside B has affinity to Afl aggregates including its oligomers and brain tissue from a mouse model of Afl pathology. In addition, plantainoside B could delay the Afl ag-gregation rate. Accordingly, plantainoside B may exert neuroprotective effects by binding to Afl oligomers, thus interrupting the binding of Afl oligomers to the cell surface. This suggests its potential application as a theranostics in AD, simultaneously diagnostic and therapeutic drugs.