Salvianolic acid B inhibits Abeta fibril formation and disaggregates preformed fibrils and protects against Abeta-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 (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.
Durairajan
Siva Sundara Kumar
SS
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong, China.
Yuan
Qiuju
Q
Xie
Lixia
L
Chan
Wing-Sai
WS
Kum
Wan-Fung
WF
Koo
Irene
I
Liu
Chenli
C
Song
Youqiang
Y
Huang
Jian-Dong
JD
Klein
William L
WL
Li
Min
M
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
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