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

[ Vol. 26 , Issue. 7 ]

Author(s):

Lichun Wang, Sitong Liu, Jiaqi Xu, Nobumoto Watanabe, Jun Di*, Wei Wei, Kevin H. Mayo, Jiang Li* and Xiaomeng Li*   Pages 780 - 789 ( 10 )

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.

Keywords:

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

Affiliation:

The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, Bioprobe Application Research Unit, RIKEN Center for Sustainable Resource Science, Wako, Saitama 351-0198, Jilin Province People’s Hospital, Chanchun 130021, The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota, Minneapolis, MN 55455, Dental Hospital, Jilin University, Changchun 130021, The Key Laboratory of Molecular Epigenetics of MOE, Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024



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