The exciting and magical journey of components from compound formulae to where they fight

With its long-term empirical clinical practice and increasing number of health benefits reported, Chinese Materia Medica (CMM) is gaining increasing global acceptance. Importantly, the identification of chemical constituents in vitro and exposed forms in vivo is a prerequisite for understanding how CMM formulae prevent and treat diseases. This review systematically summarizes the exciting and magical journey of CMM components from compound formulae to where they fight, the possible structural transformation of CMM components in vitro and in vivo, and their pharmacological contribution. When a decoction is prepared, significant chemical reactions are observed, including degradation and production of polymers and self-assembling supramolecules, leading to the construction of a component library with diverse decoction structures. After ingestion, compounds pass through the intestinal and blood-brain barriers and undergo a more wonderful journey involving the gut microbiota, microbial enzymes, and endogenous drug-metabolizing enzymes (mainly liver enzymes). At this stage, they are modified and assembled into novel and complex compounds, such as newly generated metabolites, conjugates, and self-assembling superamolecules. This review might provide a strategic orientation to explore the active compounds of CMM formulae in vivo.