Deciphering the scientific basis of traditional Chinese medicine via a multifunctional molecular networking

Traditional Chinese medicine (TCM) possesses a complex chemical system in which multiple components interact with multiple targets, which is the material basis for its efficacy but also presents a significant challenge for comprehensive constituent characterization, quality control, and mechanistic studies. Advanced analytical techniques are urgently needed to decode this complexity.

This review aims to systematically summarize the fundamental principles, methodological evolution including classical, feature-based, and building-block-based molecular networking (MN), and innovative applications of MN technology in TCM research.

A comprehensive literature search was conducted using scientific databases such as PubMed, Web of Science, and CNKI. The search focused on publications involving key terms including "molecular networking", "traditional Chinese medicine", "mass spectrometry", "natural products", and "dereplication" to identify relevant studies and applications.

Molecular networking, a high-throughput technique that organizes MS/MS data based on spectral similarity, has emerged as a crucial tool for TCM analysis. It enables the efficient mining, classification, and rapid identification of structural analogs from complex TCM samples. Its visualization capabilities not only aid in comprehensive component characterization for quality control but also facilitate the discovery of novel compounds through node associations and guide their targeted isolation. Furthermore, MN has demonstrated unique value in elucidating the complex mechanisms involved in TCM processing and preparation.

MN technology significantly advances the comprehensive analysis of TCM by providing a powerful strategy for visualizing complex chemical spaces. It holds substantial promise for enhancing quality standardization, accelerating the discovery of active constituents, and uncovering the scientific basis of TCM processing, thereby bridging traditional knowledge with modern analytical science.