Abstract

The deposition of amyloid beta (Abeta) protein is a consistent pathological hallmark of Alzheimer's disease (AD) brains; therefore, inhibition of Abeta fibril formation and destabilization of pre-formed Abeta fibrils is an attractive therapeutic and preventive strategy in the development of disease-modifying drugs for AD. This study demonstrated that Paeonia suffruticosa, a traditional medicinal herb, not only inhibited fibril formation of both Abeta(1-40) and Abeta(1-42) but it also destabilized pre-formed Abeta fibrils in a concentration-dependent manner. Memory function was examined using the passive-avoidance task followed by measurement of Abeta burden in the brains of Tg2576 transgenic mice. The herb improved long-term memory impairment in the transgenic mice and inhibited the accumulation of Abeta 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-beta-D-glucopyranose (PGG). No obvious adverse/toxic were found following treatment with PGG. As was observed with Paeonia suffruticosa, PGG alone inhibited Abeta fibril formation and destabilized pre-formed Abeta 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 Abeta 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.