Supramolecular self-assembly in Traditional Chinese Medicine: molecular mechanisms, material basis of decoction efficacy, compatibility interpretation, and biomedical applications

Abstract Traditional Chinese Medicine (TCM), characterized by multi-component and multi-target pharmacological effects, boasts millennia of clinical application. The complexity of its pharmacological material basis extends beyond individual chemical components to include physical structures formed among constituents. Supramolecular chemistry offers a new perspective for elucidating this basis. This review systematically summarizes recent advances in supramolecular self-assemblies within TCM, focusing on molecular formation mechanisms, key chemical component characteristics driving assembly, their roles in decoctions, and the supramolecular basis for "efficacy enhancement and toxicity reduction" in compatibility theory. The biomedical applications of supramolecular self‑assemblies in TCM are also reviewed. Ultimately, this work aims to offer new insights into TCM's material basis, clarify compatibility mechanisms, advance the supramolecular interpretation of TCM theories, and provide perspectives for TCM modernization and drug development. Graphical Abstract