title: Salvianolic acid B inhibits Abeta fibril formation and disaggregates preformed fibrils and protects against Abeta-induced cytotoxicty.
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.
authors.affiliation: School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
authors.forename: Siva Sundara Kumar
authors.initials: SS
authors.lastname: Durairajan
authors.forename: Qiuju
authors.initials: Q
authors.lastname: Yuan
authors.forename: Lixia
authors.initials: L
authors.lastname: Xie
authors.forename: Wing-Sai
authors.initials: WS
authors.lastname: Chan
authors.forename: Wan-Fung
authors.initials: WF
authors.lastname: Kum
authors.forename: Irene
authors.initials: I
authors.lastname: Koo
authors.forename: Chenli
authors.initials: C
authors.lastname: Liu
authors.forename: Youqiang
authors.initials: Y
authors.lastname: Song
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Huang
authors.forename: William L
authors.initials: WL
authors.lastname: Klein
authors.forename: Min
authors.initials: M
authors.lastname: Li
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology*; D052160:Benzothiazoles; D002449:Cell Aggregation / Q000187:drug effects; D045744:Cell Line, Tumor; D002942:Circular Dichroism; D003627:Data Interpretation, Statistical; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D020894:Microfibrils / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D013778:Tetrazolium Salts; D013844:Thiazoles / Q000494:pharmacology; D053630:Depsides
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D001572:Benzofurans; D052160:Benzothiazoles; D013778:Tetrazolium Salts; D013844:Thiazoles; C009462:thioflavin T; C076944:salvianolic acid B; D053630:Depsides; C022616:thiazolyl blue