Version updates of strategies for drug discovery based on effective constituents of traditional Chinese medicine

The discovery of effective constituents of traditional Chinese medicine (TCM) is an important approach in new drug development. Several well-known drugs, such as artemisinin, berberine, and ephedrine have been developed using this approach. However, the efficacy and safety of TCM, two key issues for drug development based on TCM clinical experience, remain unclear worldwide. The discovery strategy of relevant constituents is the most important step for determining efficacy and safety, which still a key scientific problem that restricts the development of new drugs. Furthermore, TCM formulas used as clinical drugs address a specific TCM syndrome (Zheng), and the complexity of the formula and vagueness of the syndrome make the identification of the effective constituents related to clinical effectiveness challenging. Over decades, researchers have developed transdisciplinary technologies and research methodologies to identify effective constituents in vivo. In this paper, the history of strategy development for identifying the effective constituents related to the clinical efficacy of TCM is reviewed and summarized. The main approaches include the phytochemical method, which involves the classical systematic separation and screening (extraction, separation, purification, structure identification, and activity test); bioactivity-guided separation; serum pharmacochemistry of TCM in vivo; and Chinmedomics, which connects in vivo constituents with the biomarkers of the relevant TCM syndrome. Chinmedomics is a promising strategy that conforms to the theory and characteristics of TCM. By clarifying the effective constituents, targets and pathways of medicines, it can promote the discovery of lead compounds and the research of innovative drugs, and continuously promote the modernization of TCM. Graphical abstract: http://links.lww.com/AHM/A64.