P3‐255: A traditional medicinal herb Paeonia suffruticosa and its active constituent 1,2,3,4,6‐penta‐O‐galloyl‐‐β‐D‐glucopyranose have potent anti‐aggregation effects on Alzheimer's amyloid β proteins in vitro and in vivo
Аннотация:The deposition of amyloid β protein (Aβ) is a consistent pathological hallmark of Alzheimer's disease (AD) brains; therefore, inhibition of Aβ fibril formation and destabilization of preformed Aβ fibrils is an attractive therapeutic and preventive strategy in the development of disease-modifying drugs for AD. In the present study, we examined the effect of Paeonia suffruticosa on the formation of Aβ aggregates and its ability to destabilize preformed Aβ fibrils in vitro by using fluorescence spectroscopy with thioflavin T and electrophoresis. Memory function was examined using the passive-avoidance task followed by measurement of Aβ burden in the brains of Tg2576 transgenic mice. This study demonstrated that Paeonia suffruticosa, a traditional medicinal herb, not only inhibited fibril formation of both Aβ1-40 and Aβ1-42 but it also destabilized preformed Aβ fibrils in a concentration-dependent manner. The herb improved long-term memory impairment in the transgenic mice and inhibited the accumulation of Aβ in the brain. Three-dimensional HPLC analysis revealed that a water extract of the herb contained several different chemical compounds including 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG). No obvious adverse/toxic were found following treatment with PGG. As was observed with Paeonia suffruticosa, PGG alone inhibited Aβ fibril formation and destabilized preformed Aβ fibrils in vitro and in vivo. Our results suggest that both Paeonia suffruticosa and its active constituent PGG have strong inhibitory effects on formation of of Aβ fibrils in vitro and in vivo. PGG is likely to be a safe and promising lead compound in the development of disease-modifying drugs to prevent and/or cure AD.
