A novel near-infrared fluorescent probe for butyrylcholinesterase: Research for screening of natural anti-AD inhibitors

• Published in: Analytica chimica acta 2024-12, Vol.1331, p.343348, Article 343348
• Main Authors: Yin, Xiaoyi, Zhang, Gaoning, Song, Guangxu, Li, Xiaoru, Liu, Xinming, Wang, Lufan, Zhang, Hai, Tang, Zhixin
• Format: Article
• Language: English
• Subjects: Alkaloids - chemistry; Alkaloids - pharmacology; Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Alzheimer's disease (AD); Animals; Butyrylcholinesterase (BuChE); Butyrylcholinesterase - chemistry; Butyrylcholinesterase - metabolism; Butyrylcholinesterase inhibitor (BuChEI); Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Drug Evaluation, Preclinical; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Humans; Infrared Rays; Matrine; Mice; NIR fluorescent probe; Quinolizines - chemistry; Quinolizines - pharmacology; Screening; Zebrafish
• ISSN: 0003-2670; 1873-4324; 1873-4324
• DOI: 10.1016/j.aca.2024.343348

Elevated levels of butyrylcholinesterase (BuChE) have the potential to be predictive in the timely detection and diagnosis of Alzheimer's disease (AD). By inhibiting of BuChE activity can raise acetylcholine levels and intervene AD processes. Therefore, BuChE as an important factor in treatment AD has been given more and more attention in clinical studies. Given the facts above, in this study, for precise monitoring of BuChE level changes and screening for possible butyrylcholinesterase inhibitor (BuChEI) for AD diagnosis and therapy, a near-infrared (NIR) fluorescence probe (NFP-BuChE) was created. The probe exhibits excellent sensitivity and selectivity for BuChE. NFP-BuChE has been successfully applied to the detection of endogenous BuChE levels in live cells, and we successfully constructed a screening system for BuChEI on cells and a novel natural efficient BuChEI (matrine) was discovered and identified, which significantly reduced BuChE activity and thus alleviated AD symptoms. Most importantly, for the first time, we measured the changes of BuChE levels in zebrafish (0–4 days) after fertilization, various organs of zebrafish, and AD zebrafish modeled by different concentrations of AlCl3 by NFP-BuChE, and at the same time, we also validated the inhibitory effect of matrine on BuChE by NFP-BuChE in zebrafish. In addition, NFP-BuChE has also been successfully used to measure the changes of BuChE levels in the brains of AD mice. These findings imply that NFP-BuChE is a potentially useful molecular tool for screening possible natural BuChEI quickly and for monitoring changes in BuChE activity, and it is expected that more value will be explored in mice. In addition, matrine and its derivatives are promising options for future Alzheimer's disease treatments. [Display omitted] •A novel near-infrared fluorescence probe NFP-BuChE for detecting BuChE activity.•The probe NFP-BuChE was used for constructing a screening system for BuChEI.•We first determined matrine with good BuChE inhibitory effect in zebrafish.•The probe NFP-BuChE was utilized to image BuChE in various organs of zebrafish.