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

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

Turn-On Fluorescent Probe Based on a Dansyl Triarginine Peptide for Ganglioside Imaging.

Gangliosides play pivotal biological roles in the animal cell membranes, and it is vital to develop fluorescent probes for imaging them. To date, various artificial receptors for ganglioside imaging have been developed; however, turn-on fluorescence imaging for gangliosides with high contrast has not been achieved. We developed a simple fluorescent probe on the basis of a dansyl triarginine peptide for turn-on ganglioside imaging on the liposome membrane. The probe bound to monosialyl gangliosides and other anionic lipids with association constants was 105 M-1, which enhanced from 6-fold to 7-fold the fluorescence intensity. Upon binding to monosialyl ganglioside-containing giant liposomes, the turn-on probe selectively enhanced the fluorescence intensity compared with the other anionic lipids. This simple peptide probe for turn-on fluorescence imaging of gangliosides would provide a novel molecular tool for chemical biology.