Abstract

In reverse pharmacology, agents that have a history of therapeutic activity are used as a starting point for drug discovery. However documented natural-product drugs from traditional medicine are generally the mixtures of compounds having a variety of pharmacological effects. It is extremely difficult to identify their active components and clarify their pharmacological mechanism due to the complex relationship between the pharmacological effect of a traditional drug itself and that of its components. In response to this situation, the key idea used in solving the problem is that traditional medicine-inspired approaches to drug discovery should start with the relevance between identifying material basis for the efficacy and clarifying pharmacological mechanism of the traditional drug. Based on the above understanding and under the background of the analgesic effect of Dragon's Blood, the methodology of reverse pharmacology was proposed, which takes the pharmacological effect of the traditional drug itself as the reference. The effects of the components and/or the combinations of components are compared with that of the traditional drug itself to obtain lead compounds with certain chemical structures. According to the principle above, the operational definition of the material basis for the efficacy of the traditional drug was established. Searching for the material basis of the efficacy of the traditional drug was converted to detecting, expressing and analyzing of the relationship between pharmacological effects of the components and/or combinations of components and the traditional drug itself. Thus the research framework of the pharmacological mechanism and the material basis of the traditional drug was built up. The research shows that following the above methodology ,the analgesic effect of Dragon's Blood could be due to the synergistic effect of its three components. In order to improve the methodology of reverse pharmacology and strengthening synergistic multicomponent drug clinical effect, Here we put forward two problems which need to be studied further: 1.How to identify molecular signaling mechanisms of synergistic components combination? 2. When material basis for the efficacy of traditional drug is composed of its multiple components, how should these components be combined to produce a stable and significant effect in vivo?