["Six-step strategy" for effective compounds in Chinese medicinal prescriptions based on in vitro-in vivo integration...

The discovery and identification of effective components are pivotal in the research on Chinese medicinal prescriptions. Given two basic conditions for effective components in Chinese medicinal prescriptions, i.e., active structure and a certain level of drug exposure in the body(including the intestine), a "six-step strategy" for the effective compounds in Chinese medicinal prescriptions based on in vitro-in vivo integration(SSS for short) has been proposed and established, as well as the key technologies. SSS contains qualitative and quantitative analyses of components in five steps, including those in Chinese medicinal extract, intestinal contents, portal vein blood, liver, and peripheral blood. The components(prototype components and metabolites) with a certain exposure level(including in the intestine) and those with large differences between in vitro content and in vivo exposure or in exposure among various parts in the body are selected as the minority prioritized candidates. The sixth step is to screen the pharmacological activity of candidate components specifically extracted from Chinese medicinal materials or artificially synthesized. SSS can significantly narrow the screening range, enhance the hit rate, and speed up the identification of effective components specifically targeting indications. Based on the effective components identified by the SSS, the "upstream" can be linked(mechanism research based on the effective components with clear structures) and the "downstream" can be combined(development of innovative component-based Chinese medicine with definite pharmacodynamic composition). In this study, the concept of component-based Chinese medicine and specific applications of SSS in the development of component-based Chinese medicine are also introduced.