Salvianolic acid B inhibits Aβ fibril formation and disaggregates preformed fibrils and protects against Aβ-induced cytotoxicty

One of the major pathological features of Alzheimer's disease (AD) is the appearance of senile plaques characterized by extracellular aggregation of amyloid beta-peptide (A beta) fibrils. Inhibition of A beta fibril aggregation is therefore viewed as one possible method to halt the progression of AD. Salvianolic acid B (Sal 13) is an active ingredient isolated from Salvia miltiorrhiza, a Chinese herbal medicine commonly used for the treatment of cardiovascular and cerebrovascular disorders. Recent findings show that Sal B prevents A beta-induced cytotoxicity in a rat neural cell line. To understand the mechanism of Sal B-mediated neuroprotection, its effects on the inhibition of A beta 1-40 fibril formation and destabilization of the preformed A beta 1-40 fibrils were studied. The results were obtained using Thioflavin T fluorescence assay and A beta aggregating immunoassay. We found that Sal B can inhibit fibril aggregation (IC50: 1.54-5.37 mu M) as well as destabilize preformed A beta fibril (IC50: 5.00-5.19 mu M) in a dose-and time-dependent manner. Sal B is a better aggregation inhibitor than ferulic acid but less active than curcumin in the inhibition of A beta 1-40 aggregation. In electron microscope study, Sal B-treated A beta 1-40 fibrils are seen in various stages of shortening or wrinkling with numerous deformed aggregates of amorphous structure. Circular dichroism data indicate that Sal B dose dependently prevents the formation of P-structured aggregates of A beta 1-40. Addition of preincubated Sal B with A beta 1-42 significantly reduces its cytotoxic effects on human neuroblastoma SH-SY5Y cells. These results suggest that Sal B has therapeutic potential in the treatment of AD, and warrant its study in animal models. (C) 2007 Elsevier Ltd. All rights reserved.