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Mol Divers (2013) 17:515524 DOI 10.1007/s11030-013-9452-z
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Salvianolic acid A, a polyphenolic derivative from Salvia miltiorrhiza bunge, as a multifunctional agent for the treatment of Alzheimers disease
Ying Ying Cao Ling Wang Hu Ge Xi Lin Lu
Zhong Pei Qiong Gu Jun Xu
Received: 26 April 2013 / Accepted: 6 May 2013 / Published online: 24 May 2013 Springer Science+Business Media Dordrecht 2013
Abstract The effects of Salvianolic acid A (Sal A) on the treatment of Alzheimers disease (AD) were investigated. Sal A signicantly inhibits amyloid beta (A) self-aggregation and disaggregates pre-formed A brils, reduces metal-induced A aggregation through chelating metal ions, and blocks the formation of reactive oxygen species (ROS) in SH-SY5Y cells. Sal A protects cells against A42-induced toxicity. Furthermore, Sal A, possibly because of the effects of decreasing toxicity effects of A species, alleviates A-induced paralysis in transgenic Caenorhabditis elegans. Circular dichroism (CD) experiments and Molecular dynamic (MD) simulations demonstrate that Sal A inhibits A self-aggregation through binding to the C-terminus of A, and therefore stabilizing the -helical conformations. Altogether, our data show that Sal A, as the multifunctional agent, is likely to be promising therapeutics for AD.
Keywords Alzheimers disease Salvianolic acid A
Amyloid Anti-oxidant Neuroprotecitve
Introduction
Alzheimers disease (AD) is a progressive neurodegenerative disorder characterized by extracellular amyloid beta (A) plaques, intracellular neurobrillary tangles, and soluble A oligomers [1,2]. Abnormal production and aggregation of A are essential pathogenic events in AD [35]. Moreover,
Y. Y. Cao L. Wang H. Ge Q. Gu (B) J. Xu
Research Center for Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China e-mail: [email protected]
X. L. Lu Z. Pei
Neurology Department of the First Afliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
A can induce oxidative stress and inammation in the brain [6,7].
In addition to A aggregation, the abnormal concentrations of metal ions, such as iron, copper, and zinc ions, occur in signicant amounts in AD brains [8]. High metal ion concentrations play important roles in A aggregation, deposition, and neurotoxicity, and induce ROS [912]. A number of in vivo studies have shown that copper, iron, and zinc ions can cause oxidative damage to neuronal cells [13,14]. Modulation of metal ions in the brain can be an effective therapeutic...