Title:A traditional Chinese Medicine, YXQN, Reduces Amyloid-induced Cytotoxicity by Inhibiting Aβ42 Aggregation and Fibril Formation
Volume: 26
Issue: 7
Author(s): Lichun Wang, Sitong Liu, Jiaqi Xu, Nobumoto Watanabe, Jun Di*, Wei Wei, Kevin H. Mayo, Jiang Li*Xiaomeng Li*
Affiliation:
- Jilin Province People’s Hospital, Chanchun 130021,China
- Dental Hospital, Jilin University, Changchun 130021,China
- The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024,China
Keywords:
Aβ42 aggregation, YXQN, Aβ-induced cytotoxicity, Alzheimer's disease, fibrogenesis, aggregation.
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.
