A Carbonyl-Trapping Mechanism-Based Automatic Mining (CTM-AM) Strategy for Accelerating the Discovery of Natural Products with Anti-Advanced Glycation End Products Activity

The
abnormal accumulation of reactive dicarbonyl compounds,
such
as methylglyoxal, was a major trigger for the formation of advanced
glycation end products (AGEs), which are closely associated with various
diseases, including diabetic complications. Natural products are considered
potentially effective candidates for preventing AGE formation. Given
the complexity of natural resources, efficient tools for identifying
natural AGE inhibitors in mixtures remain lacking. In this study,
a carbonyl-trapping mechanism-based automatic mining (CTM-AM) strategy
was developed, enabling the rapid identification of anti-AGE compounds
from natural resources through liquid chromatography–high-resolution
mass spectrometry (LC-HRMS) analysis. This workflow is based on the
characteristics of the carbonyl-trapping reaction to identify the
active peaks of candidate compounds, and subsequently applies the
approach to 48 medicinal plant extracts. Structural annotation yielded
171 high-confidence active compounds, spanning 20 classes of natural
products and encompassing a diverse array of reactive functional groups.
The results demonstrated that this workflow enables the efficient
identification of diverse carbonyl-trapping active compounds and their
products in complex natural resources. This study provides an effective
method and comprehensive information for discovering natural AGE inhibitors
while also advancing the framework for mining bioactive compounds
guided by reaction mechanisms.