Patent application of intelligent quality control technology in traditional Chinese medicine production process: a review / 中国中药杂志

In the new stage for intelligent manufacturing of traditional Chinese medicine(TCM) from pilot demonstration to in-depth application and comprehensive promotion, how to raise the degree of intelligence for the process quality control system has become the bottleneck of the development of TCM production process control technology. This article has sorted out 226 TCM intelligent manufacturing projects that have been approved by the national and provincial governments since the implementation of the "Made in China 2025" plan and 145 related pharmaceutical enterprises. Then, the patents applied by these pharmaceutical enterprises were thoroughly retrieved, and 135 patents in terms of intelligent quality control technology in the production process were found. The technical details about intelligent quality control at both the unit levels such as cultivation, processing of crude herbs, preparation pretreatment, pharmaceutical preparations, and the production workshop level were reviewed from three aspects, i.e., intelligent quality sensing, intelligent process cognition, and intelligent process control. The results showed that intelligent quality control technologies have been preliminarily applied to the whole process of TCM production. The intelligence control of the extraction and concentration processes and the intelligent sensing of critical quality attributes are currently the focus of pharmaceutical enterprises. However, there is a lack of process cognitive patent technology for the TCM manufacturing process, which fails to meet the requirements of closed-loop integration of intelligent sensing and intelligent control technologies. It is suggested that in the future, with the help of artificial intelligence and machine learning methods, the process cognitive bottleneck of TCM production can be overcome, and the holistic quality formation mechanisms of TCM products can be elucidated. Moreover, key technologies for system integration and intelligent equipment are expected to be innovated and accelerated to enhance the quality uniformity and manufacturing reliability of TCM.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines (Ⅱ): classification of tablets disintegration behavior / 中国中药杂志

In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines(Ⅰ): classification of processing routes / 中国中药杂志

Oral solid dosage(OSD) occupies a key position in the market of Chinese patent medicines and new traditional Chinese medicines. Processing route is the foundation for the research and development of traditional Chinese medicine OSDs. On the basis of prescriptions and preparation methods of 1 308 traditional Chinese medicine OSDs recorded in the Chinese Pharmacopoeia, we summarized the patterns of processing routes of both modern dosage forms(tablets, granules, and capsules) and traditional dosage forms(pills and powder) and constructed a manufacturing classification system(MCS) based on the processing routes. Based on the MCS, statistical analyses were conducted respectively on medicinal materials, pharmaceutical excipients, extraction solvents in the pretreatment process, crushed medicinal materials, methods of concentration and purification, and methods of drying and granulation, aiming to uncover the process features. The results showed that each dosage form can be prepared via different routes with different processing methods of decoction pieces and raw materials for dosage preparation. The raw materials for dosage form preparation of traditional Chinese medicine OSDs included total extract, semi-extract, and total crushed powder, which accounted for different proportions. The raw materials for traditional dosage forms are mainly decoction pieces powder. Semi-extracts are the main raw materials for tablets and capsules, which account for 64.8% and 56.3%, respectively. Total extracts are the main raw materials for granules, with a proportion of 77.8%. Compared with tablets and capsules, traditional Chinese medicine granules with dissolubility requirements had a larger proportion of water extraction process, a higher proportion of refining process(34.7%), and a lower proportion of crushed medicinal mate-rials in semi-extract granules. There are four ways to add volatile oil to the modern dosage forms of traditional Chinese medicine. In addition, some new technologies and processes have been used in concentration, filtration, and granulation processes of traditional Chinese medicine OSDs, and the application of pharmaceutical excipients is diversified. The results of this study are expected to provide reference for the processing route design and upgrading of OSDs for new traditional Chinese medicines.

Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine / 中国中药杂志

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

Four critical engineering and technical problems in manufacturing measurement of traditional Chinese medicine / 中国中药杂志

Focusing on the development and quality improvement strategy of the traditional Chinese medicine(TCM) industry, the scientific and technological innovation of the new engineering of TCM should be paid attention to solve the "stuck neck" dilemma. Under the background of the ecological and industrial revolution of the scientific and technological innovation system, the super-scale information interaction and multi-dimensional integration will inevitably lead to profound changes in the manufacturing mode of TCM. Manufacturing measurement of TCM is formed on the basis of the reliability engineering theory of process control of TCM production. It is the development extension of system theory and system science ideas and a cross-fertilization discipline that combines theory with practice and adheres to the "four-oriented" re-epistemology improvement of the TCM discipline. In response to the problems of complex raw material sources, coarse process technology, unclear material basis, and poor applicability of equipment and technology in the manufacture of TCM, the transformation research mode of "aiming at the integration of pharmaceutical industry-developing intelligent production line-enabling industrial transformation" has been developed. This paper proposed the four key engineering technical problems, i.e., the identification of critical quality attributes(CQA) in the manufacture of TCM, the quality by design(QbD) and product development of the manufacturing process of TCM, the quality transfer principle and multivariate process capability index of TCM manufacturing, and the development of measurement technology and equipment of the manufacturing measurement of TCM, to achieve the systematization of quality control indicators, real-time process control, digitalization of manufacturing process, transparency of quality transfer, and intelligent whole-process control. In this paper, the new concepts, new theories, and new technologies provide a reference for the industrialization of TCM.

The influence of pressure range on the fitting results of tablet compression equation / 药学学报

According to the commonly used tablet compressibility, compactability and tabletability equation, the influence of pressure range on the fitting results and parameters of different compression equations was studied, and the optimal pressure range of different equations was determined. Plastic material microcrystalline cellulose (MCC) PH102, brittle material spray dried lactose and Chinese medicine Sanqi were used as experimental objects, the compression curves of tablets were obtained by the combination of dies with different diameters. For Heckel equation, the shape of Heckel section of different materials is not uniform, and the specified linear fitting range cannot be obtained, therefore, different distances between fitting pressure starting point and starting point were set to observe the influence of pressure range on R2 of Heckel equation. The Kawakita equation, Gurnham equation, Ryshkewitch-Duckworth (R-D) equation and Power equation are fitted in three different pressure ranges of 15-200, 15-300 and 15-400 MPa, respectively. In order to find the best linear region of Heckel equation, the 3D scatter diagram of "starting point of pressure, pressure range and R2" is drawn. The best linear pressure ranges of Heckel curves of MCC, lactose and Sanqi were 20-170, 20-220 and 10-90 MPa, respectively. It is proved that the 3D scatter diagram is an effective method to find the linear range of Heckel equation. The change of pressure range has little influence on the curve fitting effect and compression parameters of Kawakita equation, Gurnham equation and Ryshkewitch-Duckworth equation. The low pressure range of 15-200 MPa can meet the fitting requirements of Kawakita equation, Gurnham equation, R-D equation and Power equation for different materials. Therefore, only by optimizing the pressure range, can the good fitting effect be ensured and the obtained compression parameters be more reliable and interpretable.

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.

Impact of Particle Size on Density of Binary Powder Mixture of Chinese Medicine / 中国实验方剂学杂志

Objective:To investigate the influence of particle size on density of binary powder mixture of traditional Chinese medicine （TCM）， and to provide reference for formulation design of TCM preparations. Method:Three groups of binary powder mixtures with different particle size ratio （<italic>α</italic>） were constructed， namely Oroxyli Semen-microcrystalline cellulose PH102 （MCC PH102） （<italic>α</italic>=0.071 7）， Stellariae Radix-MCC PH200 （<italic>α</italic>=0.158 7） and Angelicae Sinensis Radix-MCC KG802 （<italic>α</italic>=0.840 6）. Binary powder mixtures with nine mass ratios （90∶10， 80∶20， 70∶30， 60∶40， 50∶50， 40∶60， 30∶70， 20∶80 and 10∶90） were prepared for each group， and 27 binary powder mixtures containing TCM were obtained. The particle size distribution， density and other parameters of six single materials and 27 binary powder mixtures were characterized. Based on the packing theory and multivariate analysis， the effects of particle size related parameters on the filling structure and density of the binary powder mixtures were elucidated. Result:The <italic>α</italic> of Angelicae Sinensis Radix-MCC KG802 binary mixture system was larger than the replacement rate （<italic>α</italic>_r=0.741 0）， and its density had a good linear relationship with the mass ratio， which conformed to the replacement mechanism. The <italic>α</italic> of Oroxyli Semen-MCC PH102 binary mixture system was smaller than the critical ratio （<italic>α</italic>_c=0.154 0）， and its density was nonlinear with the mass ratio of components， which conformed to the filling mechanism. The <italic>α</italic> of Stellariae Radix-MCC PH200 binary mixture system was between <italic>α</italic>_c and <italic>α</italic>_r， its density was affected by both of replacement mechanism and filling mechanism. Based on the partial least squares （PLS） model， the variable importance in the projection （VIP） analysis further proved that the mixing mass ratio （VIP value=1.62）， <italic>α</italic> （VIP value=1.13） and <italic>D</italic>₁₀ （the corresponding particle size when the particle size distribution accumulated to 10%， VIP value=1.06） were the key factors affecting the density of binary powder mixtures of TCM. Conclusion:In the binary powder mixtures of TCM， the linearity relationship between density and mass ratio is largely depended on particle size difference of components.

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.

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.

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

The herbs for promoting blood circulation and removing blood stasis were used commonly in clinical,and most of them are pungent and bitter. In order to study the nature-effect interrelationship of the herbs for promoting blood circulation and removing blood stasis,the TCMSP platform and Cytoscape 3. 5. 1 platform were used to construct warm-pungent-liver and warm-bitter-liver of the complement and intersection protein interaction network and the target-disease network and the network module was analyzed. As a result,warm-liver target-disease network is associated with diseases such as cancer,hypertension,and depression,which exerts the efficacy of warming Yang and transforming Qi,promoting Qi and activating blood,removing blood stasis and dispersing phlegm. The bitter taste target-disease network is associated with diseases such as myocardial infarction,cancer,inflammation and other diseases,which exerts the efficacy of dissipating the stasis. The pungent taste target-disease network is associated with diseases such as cancer,cardiovascular disease,osteoporosis and other diseases,which exerts the efficacy of invigorating the circulation of blood and eliminating stagnation. The research shows that the medicinal combination of warm-pungent-liver and warm-bitter-liver has the efficacy of promoting blood circulation and removing blood stasis by regulating different targets in different disease processes.

Nature-effect relationship research of Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos based on nature combination / 中国中药杂志

Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos are commonly traditional Chinese medicines with invigorating blood circulation and eliminating blood stasis,but they are different in effects due to differences in five tastes and four properties. In this study,Salviae Miltiorrhizae Radix et Rhizoma and Carthami Flos are selected as research vectors to obtain the active ingredients and targets through TCMD,TCMSP database and Ch EMBL database. The protein interaction information of the target is used to obtain from STRING online database,then imported into Cytoscape software to plot the protein interaction network and perform GO enrichment analysis.The results show that the heart-liver protein interaction network,involving blood circulation and hepatic lipid metabolism,thereby exerting the effect of activating blood circulation. The cold-bitter protein interaction network involves the biological process of vasoconstriction,thereby exerting cooling blood and the efficacy of eliminating phlegm. The warm-pungent protein interaction network involves blood coagulation,lipid metabolism and other biological processes to play the role of phlegm pain. Through analysis,it is found that the relationship between pharmacological efficacy and medicinal properties has a certain degree of specificity,which facilitates the subsequent scientific and systematic study of medicinal properties on the basis of this study.

Nature-effect relationship research of Curcumae Longae Rhizoma,Curcumae Radix,and Curcumae Rhizoma based on nature combination / 中国中药杂志

Curcumae Longae Rhizoma,Curcumae Radix and Curcumae Rhizoma are different medicinal parts of the same plant.Nevertheless,they are different in medicinal effects due to the different Chinese herbal nature. In this study,traditional Chinese medicines database( TCMD2009),traditional Chinese medicine system( TCMSP),and Ch EMBL database were retrieved to screen the active components and targets,and construct the target PPI network. By a graph theoretic clustering algorithm identifying protein complex algorithm( IPCA),the protein modules were identified and analyzed by gene ontology( GO) enrichment. A comparative study of Curcumae Longae Rhizoma and Curcumae Radix illustrate that Curcumae Longae Rhizoma regulates blood coagulation through P2 RY12,GNG2 and other genes to exert the analgesic effect. Curcumae Radix regulates lipid metabolism,plasma lipoprotein particle levels,platelet activation,response to oxidative stress,apoptotic process through LDLR,APOB,PRKCA,SOD1,TP53 and other genes to perform a function in clearing the heart and cooling the blood. A comparative study of Curcumae Radix and Curcumae Rhizoma demonstrate that Curcumae Rhizoma on regulates the nervous system by GRIA2,GRIA4 and other genes to exert blood-breaking effect; Curcumae Radix regulates lipid metabolism,plasma lipoprotein particle levels,platelet activation,response to oxidative stress,apoptotic process by genes such as CALM1,LPL,APOB,SOD1 and TP53 to play the role of clearing heart and cooling blood. Cluster analysis of the protein interaction network of the nature combination is helpful to explain the intrinsic link between the nature combination and efficacy.

Danshen: a phytochemical and pharmacological overview / 中国天然药物

Danshen, the dried root or rhizome of Salvia miltiorrhiza Bge., is a traditional and folk medicine in Asian countries, especially in China and Japan. In this review, we summarized the recent researches of Danshen in traditional uses and preparations, chemical constituents, pharmacological activities and side effects. A total of 201 compounds from Danshen have been reported, including lipophilic diterpenoids, water-soluble phenolic acids, and other constituents, which have showed various pharmacological activities, such as anti-inflammation, anti-oxidation, anti-tumor, anti-atherogenesis, and anti-diabetes. This article intends to provide novel insight information for further development of Danshen, which could be of great value to its improvement of utilization.

Identification of metabolites of Danshensu in rats / 中国中药杂志

To identify the metabolites of Danshensu in plasma and urine in rats by using UHPLC-LTQ-Orbitrap method. After oral gavage of Danshensu CMC-Na suspension in SD rats, urine and plasma samples were collected and processed by solid phase extraction. ACQUITY UPLC BEH C₁₈ column (2.1 mm×100 mm, 1.7 μm) was utilized, with 0.1% formic acid (A)-acetonitrile (B) solution as the mobile phase for gradient elution. Negative electrospray ion mode based data-acquisition method was established to collect the mass spectrometry data of biological samples. As a result, Danshensu and 21 Danshensu Ⅰ phase and Ⅱ phase metabolites were finally identified according to the accurate mass measurements, mass fragmentation behaviors and comparing with the reference standards. The main metabolic pathways included dehydration, methylation, glucuronide conjugation, sulfate conjugation and their composite reactions. Consequently, our study expounded metabolites of Danshensu in rats based on UHPLC-LTQ-Orbitrap method and provided a reference for further researches on therapeutic material basis and mechanism of Danshensu.