School of Chinese Medicine
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 β-peptide (Aβ) fibrils. Inhibition of Aβ fibril aggregation is therefore viewed as one possible method to halt the progression of AD. Salvianolic acid B (Sal B) 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 Aβ-induced cytotoxicity in a rat neural cell line. To understand the mechanism of Sal B-mediated neuroprotection, its effects on the inhibition of Aβ1-40 fibril formation and destabilization of the preformed Aβ1-40 fibrils were studied. The results were obtained using Thioflavin T fluorescence assay and Aβ aggregating immunoassay. We found that Sal B can inhibit fibril aggregation (IC50: 1.54-5.37 μM) as well as destabilize preformed Aβ fibril (IC50: 5.00-5.19 μM) 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 Aβ1-40 aggregation. In electron microscope study, Sal B-treated Aβ1-40 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 β-structured aggregates of Aβ1-40. Addition of preincubated Sal B with Aβ1-42 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. © 2007 Elsevier Ltd. All rights reserved.
β-Amyloid fibrils, Aβ aggregating ELISA, Alzheimer's disease, Circular dichroism spectroscopy, Cytotoxicity, Electron microscopy, Salvianolic acid B, Thioflavine T
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Durairajan, Siva Sundara Kumar, Qiuju Yuan, Lixia Xie, Wing-Sai Chan, Wan-Fung Kum, Irene Koo, Chenli Liu, Youqiang Song, Jian-Dong Huang, William L. Klein, and Min Li. "Salvianolic acid B inhibits Aβ fibril formation and disaggregates preformed fibrils and protects against Aβ-induced cytotoxicty." Neurochemistry International 52.5-4 (2008): 741-750.