Article: Salvianolic acid B inhibits Aβ fibril formation and disaggregates preformed fibrils and protects against Aβ-induced cytotoxicty

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TitleSalvianolic acid B inhibits Aβ fibril formation and disaggregates preformed fibrils and protects against Aβ-induced cytotoxicty
AuthorsDurairajan, SSK2
Yuan, Q1
Xie, L2
Chan, WS2
Kum, WF2
Koo, I2
Liu, C1
Song, Y1
Huang, JD1
Klein, WL3
Li, M2
Issue Date2008
PublisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neuint
CitationNeurochemistry International, 2008, v. 52 n. 4-5, p. 741-750 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neuint.2007.09.006
AbstractOne 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.
ISSN0197-0186
2011 Impact Factor: 2.857
2011 SCImago Journal Rankings: 0.222
DOIhttp://dx.doi.org/10.1016/j.neuint.2007.09.006
ISI Accession Number IDWOS:000254968300026
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorDurairajan, SSK
dc.contributor.authorYuan, Q
dc.contributor.authorXie, L
dc.contributor.authorChan, WS
dc.contributor.authorKum, WF
dc.contributor.authorKoo, I
dc.contributor.authorLiu, C
dc.contributor.authorSong, Y
dc.contributor.authorHuang, JD
dc.contributor.authorKlein, WL
dc.contributor.authorLi, M
dc.date.accessioned2010-09-06T06:00:31Z
dc.date.available2010-09-06T06:00:31Z
dc.date.issued2008
dc.description.abstractOne 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.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationNeurochemistry International, 2008, v. 52 n. 4-5, p. 741-750 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neuint.2007.09.006
dc.identifier.doihttp://dx.doi.org/10.1016/j.neuint.2007.09.006
dc.identifier.epage750
dc.identifier.hkuros145499
dc.identifier.isiWOS:000254968300026
dc.identifier.issn0197-0186
2011 Impact Factor: 2.857
2011 SCImago Journal Rankings: 0.222
dc.identifier.issue4-5
dc.identifier.openurl
dc.identifier.pmid17964692
dc.identifier.scopuseid_2-s2.0-38349160407
dc.identifier.spage741
dc.identifier.urihttp://hdl.handle.net/10722/68014
dc.identifier.volume52
dc.languageeng
dc.publisherElsevier Ltd. The Journal's web site is located at http://www.elsevier.com/locate/neuint
dc.publisher.placeUnited Kingdom
dc.relation.ispartofNeurochemistry International
dc.relation.referencesReferences in Scopus
dc.rightsNeurochemistry International. Copyright © Elsevier Ltd.
dc.subject.meshAmyloid beta-Peptides - antagonists & inhibitors - biosynthesis - toxicity
dc.subject.meshAntioxidants - pharmacology
dc.subject.meshBenzofurans - pharmacology
dc.subject.meshCell Aggregation - drug effects
dc.subject.meshCell Line, Tumor
dc.subject.meshCircular Dichroism
dc.subject.meshData Interpretation, Statistical
dc.subject.meshEnzyme-Linked Immunosorbent Assay
dc.subject.meshHumans
dc.subject.meshMicrofibrils - drug effects - ultrastructure
dc.subject.meshMicroscopy, Electron
dc.subject.meshTetrazolium Salts
dc.subject.meshThiazoles - pharmacology
dc.titleSalvianolic acid B inhibits Aβ fibril formation and disaggregates preformed fibrils and protects against Aβ-induced cytotoxicty
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong Li Ka Shing Faculty of Medicine
  2. Hong Kong Baptist University
  3. Northwestern University