[Exploration of potential efficacy markers of Astragali Radix for invigorating Qi based on systematic traditional Chinese medicine].

Astragali Radix is the elixir for invigorating Qi, with the effects of invigorating Qi, promoting Yang and nourishing the body. With the deepening researches on the chemical constituents of Astragali Radix, it is used more extensively in clinical application. Based on systematic traditional Chinese medicine theory, in this paper, we characterized the effect of Astragali Radix on invigo-rating Qi from the molecular level, and explored the markers of Astragali Radix on invigorating Qi. Through TCMSP and ChEMBL databases, the active components-targets database of Astragali Radix was constructed to clarify the targets(elements) involved in Astragali Radix's Qi invigorating efficacy system. According to the relationship between the targets, the protein interaction network was constructed, and the network modules(structure) were divided according to the theoretic clustering algorithm molecular complex detection(MCODE), and the boundary of the Qi invigorating efficacy system was defined by the pharmacological function of Astragali Radix. The active components of Astragali Radix for invigorating Qi were characterized from the aspects of composition, target and efficacy. The results showed that eight key components of Astragali Radix, such as hederagenin, quercetin, calycosin, formononetin, jaranol, isorhamnetin, astragalosideⅢ, and 9,10-dimethoxypterocarpan-3-O-ß-D-glucoside, could act on eight functional modules composed of 17 key targets, and participate in G-protein coupled receptor protein signaling pathway, regulation of lipid metabolic process, positive regulation of nitrogen compound metabolic process, positive regulation of programmed cell death, fatty acid metabolic process and other biological processes to produce pharmacological effects such as regulating immune function, strengthening heart, protecting myocardial cells, improving material metabolism, and antioxidation effects, thus playing the role of invigorating Qi. Based on the systematic Chinese medicine theory, this study explored the effective markers of Astragali Radix at the level of molecular network, which provided new ideas for the interpretation of the effective substance basis of systematic traditional Chinese medicine and the quality control of traditional Chinese medicine. In the future, it can focus on the compatibility research of these components, and then carry out more in-depth studies on the efficacy of Astragali Radix in invigorating Qi, and strengthen the development of the corresponding pharmacological mechanism and related preparations.

[Discovery and application of traditional Chinese medicine efficacy markers based on systematic traditional Chinese medicine].

The quality marker(Q-marker) of traditional Chinese medicine(TCM) is a new concept of TCM quality control proposed in recent years. It is a hot issue in the research of modern Chinese medicine. The TCM efficacy is a high-level summary of the TCM therapeutic effect under the guidance of TCM theory. On this basis, it is of considerable significance to explore the TCM efficacy marker for the TCM modernization. However, the traditional research strategy based on the single herb and decoction piece in macro TCM level, or the drug research strategy based on the biological effect of the targets, is quite different from the characteristics of multiple components of TCM, as well as the weak and low-selective effect of Chinese medicine ingredients on targets. Therefore, how to select representative ingredients to characterize the TCM overall efficacy is a problematic point in establishing TCM efficacy markers. In this paper, the concept and method of Q-marker were introduced into the study of Chinese medicine efficacy. The research method for systematic TCM was used to systematically discuss the connotation of TCM efficacy markers, the principles of discovery and determination, common research ideas and techniques by taking the representative research results as an example. This study provides new ideas for the research and discovery of TCM efficacy markers.

[Study on components efficacy of Salviae Miltiorrhizae Radix et Rhizoma based on systematic traditional Chinese medicine].

This paper aimed to establish efficacy systems of tanshinones and salvianolic acids, two representative substances in Salviae Miltiorrhizae Radix et Rhizoma by using literature mining and biological network construction, based on systematic traditional Chinese medicine theory. The systematic study on the efficacy of traditional Chinese medicine was carried out from the basic unit, the structure and relationship between the basic units, the boundary of the research object and the function of the system, so as to explain the overall efficacy of the two kinds of components at the molecular level. Firstly, we collected the elements of the efficacy systems of these two kinds of components by literature mining, and defined their boundaries based on biological processes. After that, the structure of the efficacy systems was clarified according to the relationship in the KEGG database. Finally, the function of the efficacy systems was analyzed from the level of pharmacology, pharmacodynamics, and efficacy, revealing the scientific connotation of traditional Chinese medicine efficacy system. The results showed that there were 201 targets(elements), 12 target sets(boundary), and 12 pathway networks(structure) in salvianolic acids' efficacy system. Meanwhile, there were 189 targets(elements), 11 target sets(boundary), and 11 pathway networks(structure) in tanshinones' efficacy system. The results suggested that the functions of salvia-nolic acids' and tanshinones' efficacy systems were different in pharmacology and pharmacodynamics from aspects of elements, boundary, relationship and structure, but they were same in functional level as both of them could promote blood circulation, remove blood stasis, clear away heart-fire, relieve restlessness, and soothe the nerves. Based on systematic traditional Chinese medicine, we constructed the efficacy system of two representative components in Salviae Miltiorrhizae Radix et Rhizoma in this paper, elucidated the overall efficacy and builded the bridge between reductionism and holism in traditional Chinese medicine.

[Study on efficacy markers of Salviae Miltiorrhizae Radix et Rhizoma for promoting blood circulation and remving blood stasis based on systematic traditional Chinese medicine].

Traditional Chinese medicine for promoting blood circulation and removing blood stasis has been widely used in clinical practice. However, due to the diversity of the composition of traditional Chinese medicine and the complexity of its interaction with human body, it is difficult to apply traditional quality control ingredients to characterize its overall efficacy. Systematic traditional Chinese medicine is an effective method for studying the efficacy of traditional Chinese medicine, embodying the dialectical unity of holism and reductionism. Salviae Miltiorrhizae Radix et Rhizoma is a common traditional Chinese medicine for promoting blood circulation and removing blood stasis. In this study, we constructed a multi-dimensional network of "efficacy-pharmacological efficacy-targets-components" based on systematic traditional Chinese medicine, and discussed the discovery of the efficacy markers of Salviae Miltiorrhizae Radix et Rhizoma for promoting blood circulation and removing blood stasis. Firstly, based on the Chinese medicine efficacy-pharmacology database, the most relevant pharmacological actions(boundary) for promoting blood circulation and removing blood stasis(function) were obtained, and the target sets(structure) of the corresponding pharmacological action were obtained by the DrugBank database. Then, STRING database was used to construct protein-protein interaction network(relationship) of targets related to promoting blood circulation and removing stasis, and key targets(elements) in the network were selected by evaluating topological parameters of targets. Finally, the potential efficacy markers of Salviae Miltiorrhizae Radix et Rhizoma were predicted by molecular docking based on the key targets of promoting blood circulation and removing blood stasis. The results demonstrated that salvianolic acid B, salvianolic acid A, tanshinone Ⅱ_A and tanshinone Ⅰ were the potential markers of Salviae Miltiorrhizae Radix et Rhizoma on promoting blood circulation and removing blood stasis. Salvianolic acid B, salvianolic acid A, tanshinone Ⅱ_A had been reported to have anti-platelet aggregation, anti-thrombotic, cardiovascular protection and some other pharmacological functions. Based on systematic traditional Chinese medicine, we have preliminarily predicted the efficacy markers of Salviae Miltiorrhizae Radix et Rhizoma in promoting blood circulation and removing blood stasis in this study, providing a research method for the discovery of efficacy markers and a reference for the overall quality control of traditional Chinese medicine.

[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.