[Study on efficacy markers of heat-clearing and detoxifying effect of Lonicerae Japonicae Flos based on systematic traditional Chinese medicine].

Lonicerae Japonicae Flos has a long history of heat-clearing and detoxifying effect. The description of its efficacy in Chinese Pharmacopoeia of past dynasties is relatively stable, and it is an excellent carrier for the study of efficacy markers. Guided by the theory of systematic traditional Chinese medicine, heat-clearing and detoxifying effect efficacy system of Lonicerae Japonicae Flos was taken as an example in this study to clarify the elements(active ingredients) of Lonicerae Japonicae Flos in heat-clearing and detoxifying efficacy system, determine the boundary(signal pathway), establish the structure(system dynamics model), identify the system functions corresponding to pharmacology, efficacy and effects(heat-clearing and detoxifying effect), and explore the application of system dynamics model in the discovery of efficacy markers of traditional Chinese medicine. In this paper, the dynamic models of interleukin 1(IL-1) and interleukin 6(IL-6) in vivo were established to predict the expression of related factors in IL-1 and IL-6 signaling pathways of different components and their combinations in Lonicerae Japonicae Flos by dynamic network, so as to find the effective markers of heat-clearing and detoxification of Lonicerae Japonicae Flos. The results showed that the lower the concentration of chlorogenic acid, the higher the inhibition rate of Jun N-terminal kinase(JNK) at downstream of IL-1 by the combination of chlorogenic acid and linalool; the higher the concentration of luteolin in IL-6 pathway, the higher the inhibition rate of C-reactive protein(CRP) at downstream of IL-6 by the combination of chlorogenic acid and luteolin. It revealed that the potential efficacy markers of Lonicerae Japonicae Flos in heat-clearing and detoxifying effect based on IL-1 signaling pathway were chlorogenic acid and linalool, and the potential efficacy markers of Lonicerae Japonicae Flos in heat-clearing and detoxifying effect based on IL-6 signaling pathway were chlorogenic acid and luteolin. This study provided methodological guidance for the discovery of efficacy markers of traditional Chinese medicine.