Supramolecular strategy in traditional Chinese medicine processing: Mechanistic insights mediated by self-assembly

The processing of traditional Chinese medicine (TCM) is a critical process that upholds tradition and determines medicinal efficacy. The mechanisms underlying changes in TCM efficacy resulting from processing are currently a key focus of TCM research. Advances in supramolecular chemistry have significantly advanced the understanding of the mechanisms governing the efficacy of TCM complex chemical systems. Both the active ingredient basis and the adjuvant materials used in processing can be regarded as supramolecular units. Processing guides the TCM supermolecules to change structure through covalent forces and self-assemble non-covalently, forming soft matter aggregates that enable selective recognition, transformation, and assembly of components. These aggregates autonomously steer the entire system toward enhanced efficacy and reduced toxicity, thereby revealing the TCM's true active substance foundation. This paper highlights that the dynamic chemical system formed via supramolecular self-assembly during TCM processing can be likened to an "imprinting template" with memory function, which underlies the TCM "holistic" effects-characterized by multiple components, pathways, and targets. This study aims to provide valuable insights into TCM processing based on supramolecular development, bridging the gap between supramolecular science and TCM. Consequently, it offers profound inspiration for designing next-generation smart drug delivery systems, responsive biomaterials, and adaptive chemical systems.