Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils

Mustafa T. Ardah, Katerina E. Paleologou, Guohua Lv, Sindhu A. Menon, Salema B. Abul Khair, Jia Hong Lu, Bared Safieh-Garabedian, Abdulmonem A. Al-Hayani, David Eliezer, Min Li, Omar Ali El-Agnaf

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Compelling evidence indicates that α-synuclein (α-syn) aggregation plays a central role in the pathogenesis of Parkinson's disease (PD) and other synucleinopathies. Identification of compounds that inhibit or reverse the aggregation process may thus represent a viable therapeutic strategy against PD and related disorders. Ginseng is a well-known medicinal plant that has been used in East Asia for more than two thousand years to treat several conditions. It is now understood that the pharmacological properties of ginseng can be attributed to its biologically active components, the ginsenosides, which in turn have been shown to have neuroprotective properties. We therefore sought to determine for the first time, the potential of the most frequently used and studied ginsenosides, namely Rg1, Rg3 and Rb1, as anti-amyloidogenic agents. The effect of Rg1, Rg3 and Rb1 on α-syn aggregation and toxicity was determined by an array of biophysical, biochemical and cell-culture-based techniques. Among the screened ginsenosides, only Rb1 was shown to be a potent inhibitor of α-syn fibrillation and toxicity. Additionally, Rb1 exhibited a strong ability to disaggregate preformed fibrils and to inhibit the seeded polymerization of α-syn. Interestingly, Rb1 was found to stabilize soluble non-toxic oligomers with no β-sheet content, that were susceptible to proteinase K digestion, and the binding of Rb1 to those oligomers may represent a potential mechanism of action. Thus, Rb1 could represent the starting point for designing new molecules that could be utilized as drugs for the treatment of PD and related disorders.

Original languageEnglish
Pages (from-to)89-101
Number of pages13
JournalNeurobiology of Disease
Volume74
DOIs
Publication statusPublished - 1 Feb 2015
Externally publishedYes

Fingerprint

alpha-Synuclein
Parkinson Disease
Panax
Synucleins
Ginsenosides
Endopeptidase K
Far East
Medicinal Plants
Polymerization
Action Potentials
Digestion
Cell Culture Techniques
Pharmacology
Pharmaceutical Preparations
ginsenoside Rb1
Therapeutics

Keywords

  • Aggregation
  • Amyloid fibrils
  • Drug discovery
  • Ginsenosides
  • Parkinson's disease
  • α-Synuclein

ASJC Scopus subject areas

  • Neurology

Cite this

Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils. / Ardah, Mustafa T.; Paleologou, Katerina E.; Lv, Guohua; Menon, Sindhu A.; Abul Khair, Salema B.; Lu, Jia Hong; Safieh-Garabedian, Bared; Al-Hayani, Abdulmonem A.; Eliezer, David; Li, Min; Ali El-Agnaf, Omar.

In: Neurobiology of Disease, Vol. 74, 01.02.2015, p. 89-101.

Research output: Contribution to journalArticle

Ardah, MT, Paleologou, KE, Lv, G, Menon, SA, Abul Khair, SB, Lu, JH, Safieh-Garabedian, B, Al-Hayani, AA, Eliezer, D, Li, M & Ali El-Agnaf, O 2015, 'Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils', Neurobiology of Disease, vol. 74, pp. 89-101. https://doi.org/10.1016/j.nbd.2014.11.007
Ardah, Mustafa T. ; Paleologou, Katerina E. ; Lv, Guohua ; Menon, Sindhu A. ; Abul Khair, Salema B. ; Lu, Jia Hong ; Safieh-Garabedian, Bared ; Al-Hayani, Abdulmonem A. ; Eliezer, David ; Li, Min ; Ali El-Agnaf, Omar. / Ginsenoside Rb1 inhibits fibrillation and toxicity of alpha-synuclein and disaggregates preformed fibrils. In: Neurobiology of Disease. 2015 ; Vol. 74. pp. 89-101.
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