The Mechanism Research of Qishen Yiqi Formula by Module-Network Analysis

Qishen Yiqi formula (QSYQ) has the effect of tonifying Qi and promoting blood circulation, which is widely used to treat the cardiovascular diseases with Qi deficiency and blood stasis syndrome. However, the mechanism of QSYQ to tonify Qi and promote blood circulation is rarely reported at molecular or systems level. This study aimed to elucidate the mechanism of QSYQ based on the protein interaction network (PIN) analysis. The targets’ information of the active components was obtained from ChEMBL and STITCH databases and was further used to search against protein-protein interactions by String database. Next, the PINs of QSYQ were constructed by Cytoscape and were analyzed by gene ontology enrichment analysis based on Markov Cluster algorithm. Finally, based on the topological parameters, the properties of scale-free, small world, and modularity of the QSYQ’s PINs were analyzed. And based on function modules, the mechanism of QSYQ was elucidated. The results indicated that Qi-tonifying efficacy of QSYQ may be partly attributed to the regulation of amino acid metabolism, carbohydrate metabolism, lipid metabolism, and cAMP metabolism, while QSYQ improves the blood stasis through the regulation of blood coagulation and cardiac muscle contraction. Meanwhile, the “synergy” of formula compatibility was also illuminated

Online near-infrared analysis coupled with MWPLS and SiPLS models for the multi-ingredient and multi-phase extraction of licorice (Gancao)

Additional file 1. Table S1. The sampling intervals in different extraction phases. Table S2. The HPLC results of different indicators. Table S3. The evaluation parameters of PLS and SiPLS models

Identification of Natural Compound Carnosol as a Novel TRPA1 Receptor Agonist

The transient receptor potential ankyrin 1 (TRPA1) cation channel is one of the well-known targets for pain therapy. Herbal medicine is a rich source for new drugs and potentially useful therapeutic agents. To discover novel natural TRPA1 agonists, compounds isolated from Chinese herbs were screened using a cell-based calcium mobilization assay. Out of the 158 natural compounds derived from traditional Chinese herbal medicines, carnosol was identified as a novel agonist of TRPA1 with an EC50 value of 12.46 µM. And the agonistic effect of carnosol on TRPA1 could be blocked by A-967079, a selective TRPA1 antagonist. Furthermore, the specificity of carnosol was verified as it showed no significant effects on two other typical targets of TRP family member: TRPM8 and TRPV3. Carnosol exhibited anti-inflammatory and anti-nociceptive properties; the activation of TRPA1 might be responsible for the modulation of inflammatory nociceptive transmission. Collectively, our findings indicate that carnosol is a new anti-nociceptive agent targeting TRPA1 that can be used to explore further biological role in pain therapy

UPLC Q-TOF/MS-Based Metabolic Profiling of Urine Reveals the Novel Antipyretic Mechanisms of Qingkailing Injection in a Rat Model of Yeast-Induced Pyrexia

Fever is one of the most common clinical symptoms of many diseases. Qingkailing (QKL) injection is widely used in China as a clinical emergency medicine due to its good antipyretic effects. It is a herbal formula which is composed by eight kinds of traditional Chinese medicines (TCM). As a kind of typical multiple constituents and multiple actions of TCM, it is very difficult to elaborate the antipyretic mechanism by conventional pharmacological method. Metabonomics technique provides beneficial tool for this challenge. In this study, an ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC Q-TOF/MS) metabonomics method was developed to explore the changing process of biochemical substances in rats of yeast-induced pyrexia. Partial least squares discriminate analysis (PLS-DA) was used to distinguish the normal control group, the pyrexia model group, and the pyrexia model group treated by QKL injection. The potential biomarkers related to pyrexia were confirmed and identified. MetPA was used to find the possible metabolic pathways. The results indicated that the antipyretic effect of QKL injection on yeast-induced pyrexia rats was performed by repairing the perturbed metabolism of amino acids

Network analysis of primary active compounds in Danqi analogous formulas for treating cardiovascular disease

Objective: Used extensively to treat cardiovascular disease, Danqi analogous formulas (DQAF) include prescriptions for Danqi (DQ), Fufang Danshen (FFDS) and Qishen Yiqi (QSYQ). Differences in prescription compatibility result in varying emphases of DQAF in clinical application. Methods and results: Based on network analysis in this study, common and distinct mechanisms of DQAF actions on cardiovascular disease were analyzed at a systemic level. Components–targets–pathways models were developed by Cytoscape (http://www.cytoscape.org/); whereby, target information for active compounds was obtained based on the PharmMapper database (http://59.78.96.61/pharmmapper/), which was further used to search pathways using the Kyoto Encyclopedia of Genes and Genomes database (http://www.genome.jp/kegg/). Based on target and network analyses, we discovered RBP4 is a potential common target of DQAF, while mitogen-activated protein kinase 1 (MAPK1) and glutathione S-transferase P were potential targets of FFDS and QSYQ, respectively. Furthermore, the potential of DQAF to treat cardiovascular disease occurs through effects on the endocrine, immune, and digestive systems, in addition to lipid, sugar and amino acid metabolic pathways. Whereas FFDS exhibits effects on Toll-like receptor, transforming growth factor beta and MAPK signaling pathways; QSYQ exerts effects on cyclic adenosine monophosphate signaling, as well as metabolism of glutathione and arachidonic acid. Conclusion: This study not only reflects the formulas-effect modality of multiple compounds, targets and pathways, but also provides clues to better understand physiological mechanisms of DQAF

In silico method for studying property combination of traditional Chinese herbs

Objective: This paper discusses the composition of prescription qualitative, quantitative design principles and methods based on herbal property combination, describing the method application in new prescription design. Method: Qualitative property-combination pattern (PP) calculation was based on bipartite graphing and performing a greedy algorithm which was designed to optimize obtaining a new herbal prescription. Quantitative PP calculation was based on the qualitative computation. To calculate the Euclidean distance for the PP of the new prescription, an optimized algorithm for solving the unknown minimum Euclidean distance was used with, the new weighted proportions. Finally, non-linear optimization software was used to find the minimum Euclidean distance. Results: Using the PP of classic prescription Large Yin-Nourishing Pill, applying quantitative PP calculation a new prescription was created. Mathematical algorithms based on property combinations of traditional Chinese herbs can be applied to identify compatibility and synergies of herbs within prescriptions, especially classic formulas. Conclusion: In silico methods can then be used to create new prescriptions or modify existing ones depending on need. This type of automated approach may increase efficiency in designing new drugs based on Chinese herbs

Property combination patterns of traditional Chinese medicines

Objective: In this study, the property combinations (PCs) of single herbs, two-herb combinations, and multi-herb prescriptions were studied to determine that the property-combination patterns will be associated with these three levels. Method: By calculating the prescription PC weight, we analyzed the PCs of the single herb coptis rhizome, the two-herb combination of coptis rhizome and scutellaria root, and the classic prescriptions Coptis Decoction to Resolve Toxicity, White Tiger Decoction to Resolve Toxicity, and Peony Decoction, all three of which contain coptis and scutellaria. Results: Calculated results show that cold-bitter-lung, cold-bitter-heart, and cold-bitter-stomach are present in both Coptis Decoction and White Tiger Decoction and have the highest PC weights. The weights of coptis and scutellaria in Peony Decoction differs from in their weights in Coptis Decoction and White Tiger Decoction, in that the PCs of highest weights in Peony Decoction are cold-bitter-spleen, cold-bitter-liver, cold-bitter-large intestine, cold-sour-liver, and cold-sour-spleen. Conclusion: This novel method for exploring the properties and compatibilities of traditional Chinese herbs helps validate the combination theories of herbs. Application of this method may be valuable in designing new efficacious herbal prescriptions

Rapid Elemental Analysis and Provenance Study of Blumea balsamifera DC Using Laser-Induced Breakdown Spectroscopy

Laser-induced breakdown spectroscopy (LIBS) was applied to perform a rapid elemental analysis and provenance study of Blumea balsamifera DC. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were implemented to exploit the multivariate nature of the LIBS data. Scores and loadings of computed principal components visually illustrated the differing spectral data. The PLS-DA algorithm showed good classification performance. The PLS-DA model using complete spectra as input variables had similar discrimination performance to using selected spectral lines as input variables. The down-selection of spectral lines was specifically focused on the major elements of B. balsamifera samples. Results indicated that LIBS could be used to rapidly analyze elements and to perform provenance study of B. balsamifera