Study on Q-markers of Da Chaihu decoction based on specific chromatogram and network pharmacology / 药学学报

Da Chaihu decoction is a classic prescription for the treatment of cholecystitis that is widely used in clinical practice, and has a definite curative effect. However, due to its diverse components and complex functions, the traditional indexes fail to capture its overall efficacy. Therefore, this study analyzed and predicted the quality markers (Q-markers) of Da Chaihu decoction based on specific chromatogram and network pharmacology to provide a reference for the comprehensive control of the quality. The study obtained 35 potential practical components of Da Chaihu decoction through virtual screening. The specific chromatogram of 15 batches of Da Chaihu decoction was established by HPLC-DAD with neohesperidin as a reference. Compared with the chromatographic peaks and the reference substance, the chemical components were assigned to predict the nine components of albiflorin, paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, saikosaponin b2, saikosaponin b1 as Q-markers of Da Chaihu decoction. Finally, the network of the "components-key targets-signal pathways-biological processes" was constructed by network pharmacology to explore the mechanism of Da Chaihu decoction in treating cholecystitis to clarify the accuracy of Q-markers. The results indicated that potential Q-markers could act on multiple targets to regulate inflammatory and metabolism, and then combine to treat cholecystitis. Q-markers could combine with the pharmacologic action of Da Chaihu decoction, which could elucidate the overall efficacy of Da Chaihu decoction. This study explored the Q-markers of Da Chaihu decoction combined with the specific chromatogram and network pharmacology, which provided a basis for the quality control and evaluation of Da Chaihu decoction.

Study on discovery of efficacy markers for Dachaihu Decoction and its action mechanism / 中国中药杂志

Dachaihu Decoction is a classical Chinese herbal prescription that is effective in harmonizing lesser yang and purging internal accumulated heat. At present, it has been widely used in clinical practice, and the resulting outcomes are satisfactory. However, its quality indicators and action mechanism are still not clear. Therefore, this paper explored the efficacy markers of Dachaihu Decoction and its action mechanism based on literature mining, molecular biology, and network pharmacology, so as to better control its quality and ensure its clinical efficacy. The efficacy markers of Dachaihu Decoction were predicted and analyzed according to the "five principles" for Q-markers of Chinese herbs. Then the anti-inflammatory activity of the efficacy markers of Dachaihu Decoction was evaluated with Griess reagent after the establishment of RAW264.7 cell inflammation model in vitro with lipopolysaccharide(LPS). The potential targets of efficacy markers were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), ChEMBL, and SwissTargetPrediction, followed by the construction of the protein-protein interaction(PPI) network of the efficacy markers of Dachaihu Decoction. Topological, GO, and KEGG enrichment analysis was carried out to construct the "key target-signaling pathway-biological process" network, thus elucidating the action mechanism of the efficacy markers of Dachaihu Decoction. Saikosaponin B_2, baicalin, baicalein, wogonoside, neohesperidin, naringin, hesperidin, and paeoniflorin were considered as the potential efficacy markers of Dachaihu Decoction. The anti-inflammatory activity evaluation showed that the potential efficacy markers effectively inhibited the release of NO, exhibiting good anti-inflammatory activities. As demonstrated by network pharmacology, the efficacy markers of Dachaihu Decoction regulated the inflammatory response by acting on MAPK and NF-κB signaling pathways, the carbohydrate metabolism by HIF-1 and PI3 K-AKT signaling pathways, and the lipid metabolism by AMPK and PI3 K-AKT signaling pathways. This study discovered the efficacy markers of Dachaihu Decoction based on literature mining combined with molecular biological experiments and explored its action mechanism at the molecular level based on network pharmacology, which would provide reference for the quality control of Dachaihu Decoction and scientific basis for its clinical application.

Potential therapeutic effect of Saussureae Involucratae Herba on breast cancer and its mechanism based on network pharmacology / 中国中药杂志

As one of the most commonly diagnosed cancers in the world, female breast cancer is induced by the high level of estrogen. Saussureae Involucratae Herba(SIH), a gynecological medicinal, regulates estrogen-induced diseases. However, the therapeutic effect of SIH on breast cancer has not been reported. Therefore, this study aims to explore the potential efficacy of SIH on breast cancer based on in vitro experiment and network pharmacology. The inhibitory effect of SIH water extract on proliferation and migration of breast cancer MDA-MB-231 cells was examined. The result demonstrated SIH water extract significantly suppressed the proliferation of breast cancer cells(IC_(50)=6.47 mg·mL~(-1)) and also restricted the migration. A total of 39 components of SIH were retrieved from traditional Chinese medicine database(TCMD) and 160 targets of SIH were screened by target fishing with the PharmaDB database. The Online Mendelian Inheritance in Man(OMIM) was used to establish a 1 001-targets data set of breast cancer. Based on the overlaps(45) of targets between SIH and breast cancer, a protein-protein interaction(PPI) network was built to analyze the interactions among these targets with STRING platform and Cytoscape. Finally, through topology and GO and KEGG analysis, 8 targets, 101 pathways and 85 biological processes were found to involve the treatment of breast cancer by SIH. SIH may exert the anti-breast cancer effect by regulating cell cycle, inhibiting proliferation, migration and adhesion of cancer cells, and modulating estrogen receptor. This study clarified the mechanism of SIH in treating breast cancer, which lays a foundation for the further development of SIH.

Analysis on targets of regulating Qi and activating blood based on activity spectrum of targets / 中国中药杂志

The traditional Chinese medicines(TCM) for activating blood circulation and the TCM for regulating Qi are often used in combination in clinical practice. However, their mechanisms are still unclear. The activity spectrum of targets can fuse the active components, targets and intensity of action, which provides support for the discussion of efficacy targets. The chemical components of common TCM sets for activating blood circulation and regulating Qi, as well as the negative sets not for activating blood circulation and re-gulating Qi were obtained from the database of TCM. By the similarity analysis of chemical components in TCM for activating blood circulation and DrugBank database, the predicted targets of chemical components in TCM for activating blood circulation were obtained, and the similarity value of the two was taken as the activity value of the active components and predicted targets. Then, the component-target activity value was weighted. The activity values of herb acting on the same target were fused to construct activity spectra of targets of the herbs for activating blood circulation, herbs for regulating Qi and negative herbs. The targets whose activity values of activating blood circulation and regulating Qi were higher than those of negative herbs were selected as potential targets of efficacy. Protein-protein interaction networks were constructed for topological, GO and KEGG enrichment analysis to determine the key targets of efficacy of activating blood circulation and regulating Qi. The component-target activity information collected from DrugBank database contained 4 499 compounds, 627 targets and 11 295 action relationships. The activating blood function protein-protein interaction network contained 206 nodes and 1 728 edges, while the regulating Qi function protein-protein interaction network contained 230 nodes and 986 edges. The enrichment analysis of topology, GO and KEGG showed that TCM for activating blood circulation mainly exerted its anti-inflammatory, neuroprotective and angiogenic effects on signaling cascade pathway mediated by VEGF/VEGFR2, ERK signaling pathway, calcium signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 3(MAPK3), proto-oncogene tyrosine-protein kinase Src(SRC), mitogen activated protein kinases 1(MAPK1), epidermal growth factor receptor(EGFR), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform(PIK3 CA), peroxisome proliferators-activated receptor gamma(PPARG), nitric oxide synthase 3(NOS3), prostaglandin G/H synthetase 2(PTGS2), matrix metalloproteinase-9(MMP9), and vascular endothelial growth factor A(VEGFA). TCM for regulating Qi mainly exerted anti-inflammatory and neuroprotective effects by acting on MAPK signaling pathway and PI3 K-AKT signaling pathway, and the key targets included mitogen activated protein kinases 8(MAPK8), SRC, mitogen activated protein kinases 14(MAPK14), and RAC-alpha serine/threonine-protein kinase(AKT1), mitogen activated protein kinases 3(MAPK3). Based on the activity spectrum of targets, the targets of the TCM for activating blood and the targets of the TCM for regulating Qi were analyzed to provide reference for the study of efficacy targets of TCM, and also provide some scientific basis for clinical application.

Mechanism of Wuwei Ganlu in treatment of knee osteoarthritis:a study based on network pharmacology and molecular docking / 中国中药杂志

Wuwei Ganlu, a formula for medicated bath, consists of medicinal materials of Ephedra sinica, Platycladus orientalis, Myricaria squamosa, Artemisia carvifolia, and Rhododendron anthopogonoides, which is effective in inducing perspiration, resisting inflammation, relieving pain, regulating yellow water disease, and activating blood circulation. On this basis, a variety of formulas for Tibetan medicated bath have been derived for the treatment of diseases in internal organs, joints, nerves, etc. Modern studies have confirmed that Wuwei Ganlu has a good therapeutic efficacy on knee osteoarthritis(KOA). The present study explored the mechanism of Wuwei Ganlu in treating KOA based on network pharmacology and molecular docking. Firstly, the chemical components of Wuwei Ganlu were obtained through literature mining and database retrieval, and corresponding potential targets were predicted according to the BATMAN-TCM database. The protein-protein interaction(PPI) network was obtained after the potential targets were input into the STRING database. The network function modules were analyzed by the Molecular Complex Detection(MCODE) algorithm, and the functions of the modules were annotated to analyze the action mode of Wuwei Ganlu. Secondly, the related targets of KOA were collected through the DisGeNET database, and the overlapping targets were confirmed to analyze the mechanism of Wuwei Ganlu in treating KOA. Finally, the key targets were selected for molecular docking with the main components of Wuwei Ganlu to verify the component-target interaction. A total of 550 chemical components and 1 365 potential targets of Wuwei Ganlu were obtained. PPI analysis indicated that this formula could exert the effects of oxidation-reduction, inflammation resistance, bone absorption, bone mineralization, etc. Nineteen common targets were obtained from the intersection of potential targets of Wuwei Ganlu and KOA disease targets. It was found that the Wuwei Ganlu mainly acts on nuclear factor-κB(NF-κB), interleukin-1 beta(IL1β), tumor necrosis factor(TNF), IL6, IL1 receptor antagonist(IL1 RN), and prostaglandin-endoperoxide synthase-2(PTGS2) to treat KOA. Among the 550 chemical components of Wuwei Ganlu, 252 potential active components were docked with TNF and 163 with PTGS2, indicating good binding of the components with potential key targets. The study preliminarily explored the mechanism of Wuwei Ganlu in treating KOA to provide a reference for the further development and utilization of Tibetan medicated bath that has been included in the UN Intangible Cultural Heritage.

The mediating effect of neurotic personality between occupational stress and psychological symptoms in metro-drivers / 中国职业医学

OBJECTIVE: To explore the relationship between occupational stress response and psychological symptoms of metro-drivers and the mediating role of neurotic personality. METHODS: A total of 396 metro-drivers in a subway operating company were selected as the research subjects using judgment sampling method. Their psychological symptoms, neurotic personality and occupational stress response were evaluated using the Symptom Checklist 90, the Neurotic Subscales of NEO Five-Factor Inventory, and the Personal Strain Questionnaire of Occupational Stress Inventory Revised Edition. RESULTS: The scores of psychological symptoms, neurotic personality and occupational stress response in the metro-drivers were(148.8±42.7),(29.3±6.3) and(104.2±14.2), respectively. The occupational stress of metro-drivers was positively correlated with the psychological symptoms score(correlation coefficient was 0.45, P<0.01), and neurotic personality was positively correlated with occupational stress response and psychological symptoms scores(correlation coefficients were 0.44 and 0.53 respectively, all P<0.01). The occupational stress response of metro-drivers played a direct effect on their psychological symptoms, and the direct effect was 0.825. Neurotic personality played a partial mediating effect between occupational stress response and psychological symptoms, and the mediating effect was 0.537, accounting for 39.4% of the total effect. CONCLUSION: The neurotic personality of metro-drivers plays a partial mediating role between occupational stress response and psychological symptoms.

Identification of active components in Xuefu Zhuyu Decoction based on targets of blood-activating function / 中国中药杂志

As a classic prescription for promoting blood circulation to remove blood stasis, Xuefu Zhuyu Decoction(XFZYD) is widely used in clinical practice and has notable curative effect. Based on the key targets of activating blood circulation, this study identified the active components of XFZYD to reveal the material basis. The components of XFZYD were collected from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The molecular docking models were built for the blood-activating targets obtained from the previous study with the components of XFZYD. The top five active components with measurability for each target were selected as the potential blood-activating components in the prescription. The efficacy of the prescription can embody key pharmacological and high-content components. In this study, anti-platelet aggregation activity was used to characterize the effect of activating blood, and the in vivo experiments were conducted to verify the accuracy of the active components. A total of 210 chemical components of XFZYD were screened out from TCMSP and docked with the key targets with the function of activating blood. Ligustrazine, acteoside, naringin, etc. were selected as the potential active components for activating blood in XFZYD. The anti-platelet aggregation activity of the combination of Chuanxiong Rhizoma, Rehmanniae Radix, Aurantii Fructus, Glycyrrhizae Radix et Rhizoma, and Carthami Flos was 9.82%±5.11%. Compared with that in the control group, the platelet aggregation induced by adenosine diphosphate(ADP) was significantly inhibited in the test group(P<0.01), which verified the accuracy of the active components. This study can guide the research on the material basis of XFZYD and provide insights into the development and utilization of the classical prescription.

Material manufacturability classification in high shear wet granulation process of Chinese medicine / 中国中药杂志

The high shear wet granulation(HSWG) process of Chinese medicine has a complicated mechanism. There are many influencing factors that contribute to this process. In order to summarize the manufacturability of different kinds of materials in HSWG, this paper constructed a material library composed of 11 materials, including 4 Chinese medicine extracts and 7 pharmaceutical excipients. Each material was described by 22 physical parameters. Several binders were employed, and their density, viscosity and surface tension were characterized. Combining empirical constraints and the principle of randomization, 21 designed experiments and 8 verification experiments were arranged. The partial least squares(PLS) algorithm was used to establish a process model in prediction of the median granule size based on properties of raw materials and binders, and process parameters. The surface tension and density of binders, as well as the maximum pore saturation were identified as key variables. In the latent variable space of the HSWG process model, all materials could be divided into three categories, namely the Chinese medicine extracts, the diluents and the disintegrants. The granulation of Chinese medicine extracts required low viscosity and low amount of binder, and the resulted granule sizes were small. The diluent powders occupied a large physical space, and could be made into granules with different granule sizes by adjusting the properties of binders. The disintegrants tended to be made into large granules under the condition of aqueous binder. The combination use of material database and multivariate modeling method is conducive to innovate the knowledge discovery of the wet granulation process of Chinese medicine, and provides a basis for the formulation and process design based on material attributes.

Study on mechanism of Tibetan medicine Zuomua Decoction in treatment of hypertension based on network pharmacology and molecular docking technology / 中国中药杂志

Hypertension is a kind of chronic cardiovascular system disease caused by a series of factors and carriers dysfunction, which belongs to the category of Tibetan medicine "Chalong disease", and has a high rate of disability and mortality. Zuomua Decoction is a classical Tibetan medicine for Chalong disease, but its mechanism is not clear. Therefore, in this paper we explored the multi-components, multi-targets and multi-channels mechanism of Zuomua Decoction in the treatment of hypertension based on network pharmacology and molecular docking technology. First of all, the chemical components of Zuomua Decoction were obtained in the retrieval of traditional Chinese medicine systems pharmacology database(TCMSP), China National Knowledge Infrastructure(CNKI) and Wanfang database. The potential targets of Zuomua Decoction were predicted by BATMAN-TCM database, and the targets of hypertension were obtained by using DisGeNET database. The intersection of these two targets set was taken to obtain the potential targets of Zuomua Decoction in the treatment of hypertension, and then the chemical compositions-targets network was constructed. Secondly, the intersection targets were imported into STRING database to obtain the interaction relationship of intersection targets, and the protein interaction network of Zuomua Decoction in the treatment of hypertension was constructed in Cytoscape. Topological, GO, and KEGG enrichment analysis were used to construct the key targets-signal pathways-biological processes network diagram and explore the mechanism of Zuomua Decoction in the treatment of hypertension. Finally, the key targets were selected to construct the pharmacodynamic identification models to verify the effect mode of Zomua Decoction in treating hypertension. The results showed that there were 61 chemical components and 90 potential targets in the compounds-targets network. We obtained 21 key targets, 154 signal pathways, and 382 biological processes in topological, GO, and KEGG enrichment analysis of the protein interaction network, and in the comprehensive analysis, it was found that Zuomua Decoction could reduce blood pressure by regulating renin angiotension aldosterone system, balancing the concentration of intracellular calcium and sodium ions and regulating vasoconstriction and relaxation. ACE, AGTR1, and ADRB2 were used as the carriers for molecular docking study on the components of Zuoma Decoction, and the results showed that the chemical components of Zuomua Decoction had a good binding activity with key targets. The purpose of this study is to provide ideas for the in-depth study of Zuoma Decoction in the treatment of hypertension, and provide scientific basis for its clinical rational application.

Possible mechanisms by which Polygonati rhizoma opposes atherosclerosis based on network pharmacology and molecular docking analyses / 药学学报

Possible mechanisms by which Polygonati rhizoma opposes atherosclerosis (AS) were identified by network pharmacology and molecular docking analyses. The Traditional Chinese Medicine Database (TCMD) and the Traditional Chinese Medicine Systems Pharmacology Database (TCMSP) were utilized to identify the likely active components of Polygonati rhizoma. The potential targets set of Polygonati rhizoma were predicted with the PharmaDB database and the Swiss TargetPrediction database. The targets set for AS was retrieved by OMIM, DisGeNET and NCBI Gene database. We used the STRING platform to construct a protein-protein interaction network of the intersectional targets and performed visual analysis in Cytoscape. The key targets of Polygonati rhizoma in AS were searched by network topology and the resulting GO and KEGG enrichment was analyzed by Clue GO. In addition, the key targets were verified by molecular docking in Discovery Studio 4.0. A total of 45 active ingredients and 51 potential targets were obtained in the treatment of AS. The results of the topology analysis included five key targets: serum albumin, mitogen-activated protein kinase 3, mitogen-activated protein kinase 1, proto-oncogene tyrosine-protein kinase Src and matrix metalloproteinase-9. The 131 GO items showed that the biological process mainly involved the steroid receptor, cell response to steroid stimulation, the phosphatidylinositol-3 kinase signal pathway, and others. The KEGG pathway analysis included 37 pathways, which were closely related to peroxisome proliferation activated receptor signaling pathway, platelet activation pathway, vascular endothelial growth factor pathway, hypoxia inducible factor pathway and adhesion connection pathway. The results of molecular docking proved that the combined activity of the components with potential key targets is excellent. This study proposes mechanisms by which Polygonati rhizoma might act to reverse or minimize AS and provides a scientific basis for clinical research on Polygonati rhizoma.

Discovery and application of traditional Chinese medicine efficacy markers based on systematic traditional Chinese medicine / 中国中药杂志

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 / 中国中药杂志

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 / 中国中药杂志

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.

Exploration of potential efficacy markers of Astragali Radix for invigorating Qi based on systematic traditional Chinese medicine / 中国中药杂志

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-β-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.

Study on efficacy markers of heat-clearing and detoxifying effect of Lonicerae Japonicae Flos based on systematic traditional Chinese medicine / 中国中药杂志

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.

Lipid regulation mechanism and dosage form selection of Xixian Tongshuan Preparation based on molecular simulation methods / 中国中药杂志

Atherosclerosis is the main cause of stroke, and dyslipidemia is the most important risk factor for atherosclerosis. In this paper, pharmacophore and molecular docking models of eight key lipid-lowering targets, namely NPC1 L1, HMG-CoA reductase, SQS, MTP, CETP, PPARα, LXRα and LXRβ, were used to screen out the small molecular database of traditional Chinese medicine(TCM), which was made up of ingredients of thirteen Chinese herbal medicines contained in Xixian Tongshuan Preparation. The screening results indicated that the preparation could showed an effect in regulating lipid on target NPC1 L1, HMG-CoA reductase, LXRβ and SQS through four groups of potential active compounds, namely prupersin A in peach kernel and suffruticoside A in gastrodiaelata, limocitrin-β-D-glucoside in Ligusticum chuanxiong, 2'-(2,3-dihydroxybenzoyl)-sweroside in Pinellia ternate and quercitrin in Panax notoginseng, 4-tert-butyl-2-[(5-tert-butyl-2-hydroxy-phenyl)methoxy-methyl]-6-(hydroxymethyl)phenol in Gastrodia elata. Moreover, the properties and extraction process of the most potentialactive compounds were consistent with the preparation process of Xixian Tongshuan Capsules, which indicated that the capsule had more advantages than the pill in the existing two dosage forms of Xixian Tongshuan Preparation. This study analyzed the pharmacodynamic basis and mechanism of Xixian Tongshuan Capsules in regulating lipid for treating stroke, and provided evidence for its further research and clinical application.

Study on mechanism for treating ischemic stroke of Siegesbeckiae Herba based on network pharmacology / 中国中药杂志

Xixiancao( Siegesbeckiae Herba) has the effect of treating ischemic stroke( IS),however,the mechanism has not been fully elucidated. In this study,combined with Lipinski's five principles and Veber oral bioavailability rules,68 chemical components of Xixiancao were obtained by database and literature search. Based on the reverse targeting,248 potential targets were obtained and mapped it to the ischemic stroke target set,47 potential targets for the treatment of ischemic stroke were obtained. Molecular docking technique was used to verify that the Xixiancao component has good binding activity to potential targets. GO enrichment analysis and pathway analysis were performed on potential targets using Clue GO. GO enrichment analysis showed that Xixiancao was mainly involved in life processes such as neuronal apoptosis,cholesterol storage and blood pressure regulation. Pathway analysis showed that Xixiancao may promote vascular repairing and regeneration by regulating the expression of ADAMTS1,FLT1 and KDR in VEGFA-VEGFR2 signaling pathway,activate cell survival signals and inhibit neuronal apoptosis by regulating the expression of CAMK2 AA,MDM2,MAPK1,MAPK3,CDK5 and MAPK10 in brain-derived neurotrophic factor signaling pathway and PI3 K-Akt signaling pathway. Lipid homeostasis and inflammation may also be regulated by Xixiancao through regulating the expression of ESR1,NR1 H3,PPARA,PPARG in the nuclear receptor signaling pathway. In addition,Xixiancao could also prevent platelet aggregation by regulating the expression of ITGA2 B,F2,F10,and ALB,and play an antithrombotic role. The results of this study indicate that Xixiancao plays an important role in the treatment of ischemic stroke mainly through anti-thrombosis,promoting angiogenesis,protecting neurons,anti-inflammatory and regulating blood pressure and lipids.

Anti-inflammatory mechanism of Xixian Tongshuan Preparation based on molecular simulation methods / 中国中药杂志

Inflammatory response is caused by exogenous and endogenous stimuli,resulting in a non-specific resistance reaction.After acute ischemic cerebral infarction,inflammatory factors gather and adhere in the ischemic area of leukocyte infiltration,and the released inflammatory factors causes the injury cascade,aggravate the brain tissue damage and the symptoms of neurological deficits,and hinder the repair of brain neurons and the recovery of nerve function. In this paper,the key targets in the arachidonic acid metabolic pathway were studied. The Hiphop pharmacophore model of s PLA2-ⅡA and COX-2 inhibitors was built. According tothe two previously constructed 5-LOX and LTA4 H target inhibitors,the pharmacophore model was used to initially screen out the composition database of all of 13 traditional Chinese medicines in Xixian Tongshuan Preparation. The molecular matching study was carried out by selecting the matching value greater than 0. 6,and the component with the CDOCKER score greater than 80% of the original ligand score was used as the potential active inhibitor of the target. Considering the pharmacophore matching value,the molecular docking score and the interaction between the components and the target,one Chuanxiong component and one safflower component were selected as potential inhibitors of s PLA2-ⅡA; two Chuanxiong components,two Panax notoginseng,one safflower component,one angelica component,one valerian component were taken as a potential inhibitor of COX-2; two Gentiana components,one safflower component,one valerian component,one P. notoginseng component and one Angelica component were taken as potential inhibitors of 5-LOX; and two Gentiana components,two Chuanxiong components,and two safflower components were taken as potential inhibitors of LTA4 H. This study screened out the potential inhibitors of the four targets in a high-efficiency and low-cost manner,and explained that Xixian Tongshuan Preparation showed an effect in the treatment of inflammatory responses caused by ischemic stroke by acting both LOX pathway and COX pathway in the metabolic pathway.

Nature-effect relationship research of traditional Chinese medicine for promoting blood circulation and removing blood stasis based on nature combination / 中国中药杂志

The efficacy of traditional Chinese medicine is the therapeutic effect of the drug on the body. The nature of traditional Chinese medicine is a further generalization of the effect of efficacy,and there is an intrinsic relationship between efficacy and nature of traditional Chinese medicine. In this study,the nature-effect relationship is found on the whole level,through the research mode of " nature combination-targets of traditional Chinese medicine-modules of protein interaction network-efficiency". The results showed that the warm-pungent-liver protein interaction network mainly participated in lipid catabolic process,blood coagulation,platelet activation,heme oxidation,platelet degranulation,apoptotic process,acute inflammatory response to exert the effect of anti-tumor,antithrombotic,anti-myocardial ischemia and anti-inflammatory.

Nature-effect relationship research of cold and warm medicinal properties of traditional Chinese medicine for promoting blood circulation and removing blood stasis based on nature combination / 中国中药杂志

Traditional Chinese medicine for promoting blood circulation and removing blood stasis is a kind of drug with cold or warm medicinal properties which is commonly used in clinical practice. It is an excellent carrier for studying the nature-effect relationship of traditional Chinese medicine. Therefore,this study will acquire the main active components and targets based on the drug-based research method. The Cytoscape 3. 5. 1 platform was used to construct the protein interaction network,and the Bin GO plug-in was used to perform functional annotation and statistical analysis on the identified functional modules. The results showed that the bitter-liver protein interaction network mainly participates in cell cycle process,lipid catabolic process,blood circulation to exert the effect of promoting blood circulation and removing blood stasis; the cold protein interaction network mainly participates in vasoconstriction through targets such as EDNRA,regulates blood coagulation through targets such as PLAU,and thus exerts the effect of cooling blood and eliminating phlegm; warm protein interaction network mainly participates in the regulation of platelet activation through targets such as P2 RY12,thereby exerting the effect of promoting blood circulation,relieving pain and relieving pain. This study explains the common characteristics of the bitter-liver combination and the specific characteristics of cold or warm medicinal properties from the molecular network level,which provides a new idea for the intrinsic relationship between the medicinal properties and efficacy of traditional Chinese medicine.