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

Neurochem Int. Mar-Apr 2008;52(4-5):741-50. doi: 10.1016/j.neuint.2007.09.006. Epub 2007 Sep 16.

Abstract

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 (Abeta) fibrils. Inhibition of Abeta 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 Abeta-induced cytotoxicity in a rat neural cell line. To understand the mechanism of Sal B-mediated neuroprotection, its effects on the inhibition of Abeta1-40 fibril formation and destabilization of the preformed Abeta1-40 fibrils were studied. The results were obtained using Thioflavin T fluorescence assay and Abeta aggregating immunoassay. We found that Sal B can inhibit fibril aggregation (IC(50): 1.54-5.37 microM) as well as destabilize preformed Abeta fibril (IC(50): 5.00-5.19 microM) 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 Abeta1-40 aggregation. In electron microscope study, Sal B-treated Abeta1-40 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 beta-structured aggregates of Abeta1-40. Addition of preincubated Sal B with Abeta1-42 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / biosynthesis
  • Amyloid beta-Peptides / toxicity*
  • Antioxidants / pharmacology*
  • Benzofurans / pharmacology*
  • Benzothiazoles
  • Cell Aggregation / drug effects
  • Cell Line, Tumor
  • Circular Dichroism
  • Data Interpretation, Statistical
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Microfibrils / drug effects*
  • Microfibrils / ultrastructure
  • Microscopy, Electron
  • Tetrazolium Salts
  • Thiazoles / pharmacology

Substances

  • Amyloid beta-Peptides
  • Antioxidants
  • Benzofurans
  • Benzothiazoles
  • Tetrazolium Salts
  • Thiazoles
  • thioflavin T
  • salvianolic acid B
  • thiazolyl blue