A Carbonyl-Trapping Mechanism-Based Automatic Mining (CTM-AM) Strategy for Accelerating the Discovery of Natural...

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.