Construction of a robust fluorescent probe for the rapid evaluation of natural products' inhibition of Alzheimer's disease.

Abstract

Peroxynitrite (ONOO-) is a key oxidative stress biomarker for Alzheimer's disease (AD), and elevated levels of ONOO- in the brain directly reflect the extent of oxidative stress-induced damage in AD. To enable in situ real-time monitoring of ONOO-, this study designed and synthesized a ratiometric near-infrared fluorescent probe (BF) based on a D-π-A framework. The probe BF emits near-infrared fluorescence; upon interaction with ONOO-, BF's intrinsic ICT is weakened, causing a blue shift in its emission and resulting in a red-to-green ratio change. When applied to PC12 cells and AD model mice, BF enables real-time ratiometric imaging monitoring of changes in ONOO- levels within the cells and the mouse brain. Furthermore, through molecular docking, neobavaisoflavone (with curcumin as a control) was screened as an intervention drug; BF successfully monitored the real-time dynamic downregulation of ONOO-, and the signal recovery in the neobavaisoflavone group was superior to that in the curcumin group and the model group. This study established a rapid evaluation platform centered on real-time imaging with near-infrared ratiometric probes, which not only enables in situ dynamic monitoring of AD-related ONOO- but also provides an intuitive and reliable visualization method for the rapid assessment of the efficacy of anti-AD candidate drugs.