Baicalein Inhibits Formation of α-Synuclein Oligomers within Living Cells and Prevents Aβ Peptide Fibrillation and Oligomerisation

Jia Hong Lu, Mustafa Taleb Ardah, Siva Sundara Kumar Durairajan, Liang Feng Liu, Li Xia Xie, Wang Fun David Fong, Mohamed Y. Hasan, Jian Dong Huang, Omar Ali El-Agnaf, Min Li

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Abnormal protein aggregation in the brain is linked to the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD). Recent studies revealed that the oligomeric form of aggregates is most likely the toxic species, and thus could be a good therapeutic target. To screen for potent inhibitors that can inhibit both oligomerisation and fibrillation of α-synuclein (α-syn), we systematically compared the antioligomeric and antifibrillar activities of eight compounds that were extracted from Chinese herbal medicines through three platforms that can monitor the formation of α-syn fibrils and oligomers in cell-free or cellular systems. Our results revealed that baicalein, a flavonoid extracted from the Chinese herbal medicine Scutellaria baicalensis Georgi ("huang qin" in Chinese), is a potent inhibitor of α-syn oligomerisation both in cell-free and cellular systems, and is also an effective inhibitor of α-syn fibrillation in cell-free systems. We further tested the protective effect of baicalein against α-syn-oligomer-induced toxicity in neuronal cells. Our data showed that baicalein inhibited the formation of α-syn oligomers in SH-SY5Y and Hela cells, and protected SH-SY5Y cells from α-syn-oligomer-induced toxicity. We also explored the effect of baicalein on amyloid-β peptide (Aβ) aggregation and toxicity. We found that baicalein can also inhibit Aβ fibrillation and oligomerisation, disaggregate pre-formed Aβ amyloid fibrils and prevent Aβ fibril-induced toxicity in PC12 cells. Our study indicates that baicalein is a good inhibitor of amyloid protein aggregation and toxicity. Given the role of these processes in neurodegenerative diseases such as AD and PD, our results suggest that baicalein has potential as a therapeutic agent for the treatment of these devastating disorders. Arrested aggregation: Baicalein, a flavonoid from the Chinese herbal medicine Scutellaria baicalensis Georgi, is a potent inhibitor of α-syn oligomerisation both in cell-free and cellular systems, and is also a effective inhibitor of α-syn fibrillation in cell-free systems. It inhibits the formation of α-syn oligomers in SH-SY5Y and Hela cells, and protects SH-SY5Y cells from α-syn-oligomer-induced toxicity.

Original languageEnglish
Pages (from-to)615-624
Number of pages10
JournalChemBioChem
Volume12
Issue number4
DOIs
Publication statusPublished - 7 Mar 2011
Externally publishedYes

    Fingerprint

Keywords

  • Alpha-synuclein
  • Amyloid beta-peptides
  • Baicalein
  • Neurological agents
  • Oligomerization

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

Cite this

Lu, J. H., Ardah, M. T., Durairajan, S. S. K., Liu, L. F., Xie, L. X., Fong, W. F. D., Hasan, M. Y., Huang, J. D., Ali El-Agnaf, O., & Li, M. (2011). Baicalein Inhibits Formation of α-Synuclein Oligomers within Living Cells and Prevents Aβ Peptide Fibrillation and Oligomerisation. ChemBioChem, 12(4), 615-624. https://doi.org/10.1002/cbic.201000604