A traditional Chinese Medicine, YXQN, Reduces Amyloid-induced Cytotoxicity by Inhibiting Aβ42 Aggregation and Fibril Formation

Author(s): Lichun Wang, Sitong Liu, Jiaqi Xu, Nobumoto Watanabe, Jun Di*, Wei Wei, Kevin H. Mayo, Jiang Li*, Xiaomeng Li*

Journal Name: Current Pharmaceutical Design

Volume 26 , Issue 7 , 2020

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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.

Keywords: Aβ42 aggregation, YXQN, Aβ-induced cytotoxicity, Alzheimer's disease, fibrogenesis, aggregation.

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