A traditional Chinese medicine, YXQN, reduces amyloid-induced cytotoxicity by inhibiting Aβ42 aggregation and fibril formation

Lichun Wang, Sitong Liu, Jiaqi Xu, Nobumoto Watanabe, Jun Di, Wei Wei, Kevin H. Mayo, Jiang Li, Xiaomeng Li

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Introduction: The accumulation of amyloid-β peptide (Aβ) decreases cerebral blood flow in elderly people with Alzheimer’s disease (AD) and is believed to be the initiator of this disorder. As a traditional Chinese medicine, Yangxue Qingnao (YXQN) improves cerebral insufficiency and attenuates cognitive impairment, showing potential against AD. But whether YXQN has the ability to block Aβ self-aggregation is rarely reported. Objective: Here, we investigate the effects of YXQN on Aβ accumulation and its mediated cytotoxicity using a range of biochemical, biophysical, and cell-based approaches. Methods: Thioflavin T assay, transmission electron microscope, and 1H NMR experiments were used to investigate the effects of YXQN on Aβ fibrogenesis and aggregation. Far-UV CD spectra were acquired to assess the alteration of YXQN on the conformation of the amyloid protein. Three short Aβ42 peptides (AA 1-16, AA 17-33 and AA 28-42) were designed to analyse the Aβ42 epitope to which YXQN components bind. The effect of YXQN on Aβ-induced cytotoxicity was investigated through SH-SY5Y cell viability assay. Results: We provide evidence showing that YXQN clearly reduces Aβ42 fibrillogenesis and alters its β-sheet conformation, indicating the inhibition of primary nucleation of amyloid protein. Using the different Aβ short peptides, residues 17-33 were identified as the target epitope for YXNQ components interacting with Aβ42. Furthermore, in the SH-SY5Y cell injury model, our data show that high-dose YXQN attenuates amyloid-induced cytotoxicity approximately 60% and effectively ameliorates cell distortion in morphology. Conclusion: Based on these results, YXQN exerts a neuroprotective effect by inhibiting Aβ42 toxic aggregation, which has the potential to combat AD.

Original languageEnglish (US)
Pages (from-to)780-789
Number of pages10
JournalCurrent pharmaceutical design
Volume26
Issue number7
DOIs
StatePublished - Jan 1 2020

Keywords

  • Aggregation
  • Alzheimer’s disease
  • Aβ-induced cytotoxicity
  • Aβ42 aggregation
  • Fibrogenesis
  • YXQN

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