High-throughput screening for amyloid-β binding natural small-molecules based on the combinational use of biolayer interferometry and UHPLC−DAD-Q/TOF-MS/MS

Acta Pharmaceutica Sinica B

Gan Qiao¹  Dalian Qin²  Betty Yuen-Kwan Law³  Jianming Wu³  Chonglin Yu³  Fengdan Zhu³  Anguo Wu³  Minsong Guo³  Wenqiao Qiu³  Yong Tang³  Xiaogang Zhou³  Lu Yu⁴ 

[1] Department of Neurosurgery Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu 610000, China;State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau 999078, China;Sichuan Key Medical Laboratory of New Drug Discovery and Druggability Evaluation, Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica, School of Pharmacy, Education Ministry Key Laboratory of Medical Electrophysiology, Southwest Medical University, Luzhou 646000, China;State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Taipa, Macau 999078, China;

关键词: Alzheimer's disease;    High-throughput screening;    Biolayer interferometry;    UHPLC−DAD-Q/TOF-MS/MS;    Kai-Xin-San;   

DOI  :  

来源: DOAJ

【 摘 要 】

Discovery of drugs rapidly and effectively is an important aspect for Alzheimer's disease (AD). In this study, a novel high-throughput screening (HTS) method aims at screening the small-molecules with amyloid-β (Aβ) binding affinity from natural medicines, based on the combinational use of biolayer interferometry (BLI) and ultra-high-performance liquid chromatography coupled with diode-array detector and quadrupole/time-of-flight tandem mass spectrometry (UHPLC−DAD-Q/TOF-MS/MS) has been firstly developed. Briefly, the components in natural medicines disassociated from biotinylated Aβ were collected to analyze their potential Aβ binding affinity by UHPLC−DAD-Q/TOF-MS/MS. Here, baicalein was confirmed to exhibit the highest binding affinity with Aβ in Scutellaria baicalensis. Moreover, polyporenic acid C (PPAC), dehydrotumulosic acid (DTA), and tumulosic acid (TA) in Kai-Xin-San (KXS) were also identified as potent Aβ inhibitors. Further bioactivity validations indicated that these compounds could inhibit Aβ fibrillation, improve the viability in Aβ-induced PC-12 cells, and decrease the Aβ content and improve the behavioral ability in Caenorhabditis elegans. The molecular docking results confirmed that PPAC, DTA, and TA possessed good binding properties with Aβ. Collectively, the present study has provided a novel and effective HTS method for the identification of natural inhibitors on Aβ fibrillation, which may accelerate the process on anti-AD drugs discovery and development.

【 授权许可】

Unknown