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.
Bibliographical noteFunding Information:
This study was supported by grants from the Ministry of Science and Technology (2016YFE0128500), Jilin Provincial Science & Technology Department (20180414057GH and 20170204009YY), Changchun Science & Technology Department (17YJ006 and 17YJ001), Jilin Province Development and Reform Commission (2016C047-3 and 2016C048-3), University S & T Innovation Platform of Jilin Province for Economic Fungi (#2014B-1), National Natural Science Foundation of China (Nos. 31870758 and 30871301), and the Program for Introducing Talents to Universities (No. B07017).
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- Alzheimer’s disease
- Aβ-induced cytotoxicity
- Aβ42 aggregation