By using the integrated pharmacology platform and the big data of traditional Chinese medicine combined with the pharmacology thinking of "principle-recipe-composition-target-pathway-activity" in this study, we predicted the material basis and mechanisms of Bupleuri Radix and Scutellariae Radix drug pair for the treatment of diabetes. Fifty-nine active components were predicted, which included saponins, flavones, essential oil, fatty acids and so on. They acted on twenty-two direct targets and twenty-six main pathways respectively.The known disease targets of diabetes include arginine vasopressin receptor gene (AVP), retinoblastoma (RB1), receptor active modified protein (RAMP), platelet growth factor receptor (PDGFR), insulin receptor (INSR), α-glucosidase (GAA), etc. The pathways with diabetes effect involves endocrine system, circulatory system, digestive system, thyroid hormone signaling pathway, ErbB signaling pathway, PI3K-Akt signaling pathway, lipid metabolism and other related biological processes and metabolic pathways. The results of virtual screening in molecular docking technology indicate that flavonoids from Bupleuri Radix and Scutellariae Radix drug pair can easily form good docking mode and high affinity with peroxisome proliferators activated receptor γ (PPAR-γ) and glycogen synthase kinase-3β (GSK-3β), showing antidiabetic activity. The study provides information for the treatment of diabetes by Bupleuri Radix and Scutellariae Radix drug pair, and a new thought for the study of drug pair and complex prescription.

The medication rules of high frequency herb-pairs containing Codonopsis pilosula (Dangshen) were analyzed with data mining tools, and the molecular mechanisms of these herb-pairs on the gastrointestinal diseases were predicted with the network pharmacology. The R language association rules were used to mine the high frequency herb-pairs from TCM formulae containing Dangshen, and these herb-pairs would be screened out, which satisfied the following requirements with support ≥ 0.3 and confidence ≥ 0.9 at the same time. Using the Integrated Pharmacology Platform of Traditional Chinese Medicine (TCMIP) to predict the key core targets of the high frequency herb-pairs, the network of Chinese medicine-compound-target-pathway related to Dangshen were built to explore the preventing and treating molecular mechanism on gastrointestinal diseases. At last, the relation of the main active components from Dangshen and its herbal pairs with target proteins were validated by Systems Dock Web Site. The 185 formulae were selected from 543 formulae containing Dangshen, and 6 herbal pairs with Dangshen, which includes Angelica (Danggui), Licorice (Gancao), Atractylodes macrocephala (Baizhu), Poria cocos (Fuling), dried tangerine peel (Chenpi) and Astragalus membranaceus (Huangqi), were discovered with Apriori algorithm. The combination of 6 herbal pairs is similar to Bu Zhong Yi Qi Decoction; 6 herbal pairs with Dangshen were related to the target of POMC, OPRM1, CCR9 and HTR2C in TCMIP. The known targets (HTR2C, POMC, OPRM1, CCR9, OPRD1) and potential drug-targets (GNB1, GCK, SDHD, SLC25A2, DHRS4) for gastrointestinal diseases were predicted about the high frequency pairs with Dangshen. The results of GO enrichment analysis showed that the biological function was mainly located in the mitochondria and myelin sheath, and involved in the biological processes of three carboxylic acid cycle, platelet activation, and aspartic acid metabolism. KEGG pathway enrichment analysis showed that the main metabolic pathways related with Dangshen pairs involved amino acid metabolism, energy metabolism and endocrine metabolism. The prediction results showed many targets of the frequency herbal pairs with Dangshen preventing and treating gastrointestinal diseases were related with nerve cells. These herbal pairs could prevent and treat the gastrointestinal diseases through the neuroendocrine system and the brain gut axis.

This study was designed to explore the mechanism of total flavonoids of Astragali Radix (TFA) in treating nephrotic syndrome through establishing the active components-targets network and protein-protein interaction (PPI) networks and analyzing the functions and pathways involved in the targets. The main active ingredients of TFA were obtained by ¹H NMR and LC-MS, TCMSP and TCMID database. PharmMapper, SEA, SIB, HOME-NCBI-GENE, GeneCards and OMIM were used to predict and screen the active components of TFA. The Cytoscape software was used to construct the active components-targets network and protein-protein interactions network. The relation between the main active ingredients and targets were validated by Systems Dock Web Site. The GO and KEGG pathways involved in the targets were analyzed by ClueGO software. The target organ distribution was assigned by the BioGPS database. The results showed that 29 active components and 50 targets of TFA were screened and predicted. The network results showed that the TFA were mainly involved in biological processes such as inflammatory reaction process, oxidative stress process, apoptosis and autophagy, and played a role in the regulation of AGE-RAGE, PI3K/Akt, VEGF, IL-17 and MAPK signaling pathways to treat the nephrotic syndrome. This study reflects the characteristics of multi-components, multi-targets and multi-pathways of TFA, which provides new ideas and clues for further research on the mechanism of anti-nephrotic syndrome effects of TFA.

Fructose 1, 6-bisphosptase (FBPase), a second rate-limiting enzyme in gluconeogenesis, has an important role in the control of gluconeogenesis, which involves in energy metabolism and glucose homeostasis. Inhibitors of FBPase exhibit an anti-diabetic activity. Some of FBPase inhibitors have entered the stage of clinical trials, which indicates that FBPase is a promising therapeutic target for the discovery and development of hypoglycemic drugs. In addition, recent studies have shown that FBPase can be used to treat other diseases such as the initiation and development of tumors in several cancer types. Here, we provide a review of the biological characteristics of FBPase and contributions of FBPase on gluconeogenesis and insulin secretion, the research and development of FBPase inhibitors and the regulatory role of FBPase in other diseases.

This study was designed to explore the impact of Huanglian Jiedu Decoction (HLJDT) on macrophage inflammation reaction using the network pharmacology method. Glycolysis, sphingolipid metabolism and glutamine metabolism were also investigated for "multi-component, multi-target and multi-pathway", which supports a foundation for drug innovative research. The TCMSP database was used to screen the active components of HLJDT, the target protein predicted by PharmMapper database and the DAVID database for pathways annotation and analysis. The Cytoscape 3.2.1 software was used to construct the active componenttarget-pathway network map and GENEMANIA database for protein interaction analysis. System Dock Database Site is used in verification of molecular docking. The results showed that 84 active ingredients were screened in HLJDT with a total of 111 target targets. Fourteen pathways are affected according to 13 macrophage-related inflammatory proteins, and 8 pathways including 34 target proteins from glycolysis, sphingolipid metabolism and glutamine metabolism. Inflammation-related proteins and metabolism-related proteins can interact with each other through physical correlation, protein co-expression, etc. Berberine, baicalin and geniposide combined well with 5 important targets. Huanglian Jiedu Decoction may act on the glycolysis and sphingolipid pathways to regulate macrophage inflammatory responses.

The aim of this study was to discover the pharmacological mechanism of Compound Xueshuantong in the treatment of diabetic retinopathy using network pharmacology. TCMSP software was used to search the active ingredients of Compound Xueshuantong, and the targets of its active ingredients were obtained. The targets of diabetic retinopathy were searched by OMIM, TTD, pharmGkb, DiGSeE and GAD database. The same 37 targets were analyzed by GO and KEGG using DAVID software. The results were verified using the SystemsDock. Cytoscape 3.6.1 software was used to establish an ingredient-target-pathway network model. Network pharmacological studies suggest that Compound Xueshuantong treated diabetic retinopathy through the vascular endothelial growth factor signaling pathways, mitogen-activated protein kinase signaling pathways and Toll-like receptor signaling pathways. Compound Xueshuantong alleviated diabetic retinopathy through multi-component, multi-target, and multi-pathway. This study provides a theoretical basis for further elucidation of the pharmacological mechanism of Compound Xueshuantong in the treatment of diabetic retinopathy.

The study was designed to explore the active components and mechanism of Kai Xin San in the treatment of Alzheimer's disease (AD) based on network pharmacology. All targets related to AD were researched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Therapeutic Targets Database (TTD). The common targets obtained by two databases were determined as candidate proteins involved in AD. All active components related to Kai Xin San were researched from ADME (absorption, distribution, metabolism and excretion). PharmMapper was used to obtain the primary candidate targets of Kai Xin San. The corresponding gene name of each target protein was obtained from the UniProt database and selected human target proteins. Finally, the target proteins related to AD by Kai Xin San were acquired; Cytoscape 3.5.1 was used to construct the topology analysis for the active ingredient-AD target interaction network of Kai Xin San. According to STRING database and DAVID annotation databases, Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the targets was performed. The network pharmacology analysis results were verified by Discovery Studio molecular docking software. There were 31 components meeting the conditions of ADME and 8 targets relating to AD. Thirteen kinds of biological process, 7 related to molecular function and 11 related to cellar components, were included in 31 GO entries. There were 5 KEGG pathways, involving the calcium signaling pathway and PI3K-Akt signaling pathway. The docking results of Discovery Studio showed that active ingredients of Kai Xin San and the positive controls all have good binding activity with important targets. In conclusion, the Kai Xin San as applied for treating AD has the advantages of multi-components and targets, to investigate the active components and mechanism of Kai Xin San for treating AD based on network pharmacology to eludicate possible studies of the mechanisms of action.

This study was designed to explore the anti heart failure mechanisms of the compatibility of Gualou with Xiebai based on network pharmacology in rat model of myocardial ischemia-reperfusion injury. Using the databases of Traditional Chinese Medicine Database@Taiwan (TCM Database@Taiwan), Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Drug Repositioning and Adverse Drug Reaction Chemical-Protein Interactome (DRAR-CPI) and Universal Protein Resource (Uniprot) to screen compounds and predict the target of active components, the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, we predicted the biological pathway and signal pathway in the compatibility of Gualou with Xiebai. The effects of Gualou Xiebai dropping pills on the apoptosis of myocardial cells and the expression of protein kinase B (Akt), p-Akt and cysteine aspartate-specific proteinase (caspase-3) protein were examined in the related signal pathway phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) of myocardial ischemia reperfusion injury in rats. Twenty two compounds, such as 10 α-cucurbita-5, 24-diene-3β-ol and macrostemonoside were found to protect rats from heart failure through multiple targets, multiple biological pathways and multiple pathways, involving biological pathways such as hormone stimulation reaction, phosphorylation, apoptosis regulation, and signaling pathways such as insulin, mitogen-activated protein kinase (MAPK), cell apoptosis and so on. After the intervention of Gualou Xiebai dropping pills, the PI3K-Akt signaling pathway was activated to promote the phosphorylation of Akt protein, reduce the expression of caspase-3 protein, inhibit apoptosis and protect the myocardium. The data verify the results of the network pharmacology, and explain the mechanisms of anti-heart failure activity of combination of Gualou with Xiebai.

The objective of this study is to develop an in vitro screening method for nasal absorption of insulin. First, the adaptability of in situ rat nasal perfusion test for the study of insulin was investigated. It was found that insulin was liable to be absorbed on the silicone tube and the traditional method is not suitable. However, addition of 0.001% Labrasol into the perfusate can effectively solve this problem. A modified method suitable for in situ rat nasal perfusion of insulin was established with the addition of 0.001% Labrasol into the perfusate. Using the modified method, effect of pH and drug concentration on the absorption of insulin in the nasal cavity was further investigated. The results suggest that compared with pH 4.5 and pH 7.4, the drug absorption rate was the lowest at pH 6.0. The intranasal absorption mechanism of insulin may be passive diffusion.

The particle diameters of active pharmaceutical ingredient (API) and excipients are important factors to the quality of preparations and have great significances in the reverse engineering to brand products and the consistent evaluation of generic drugs. In this study, a novel method was established for particle size determination to identify the selected component and eliminate other interferential particles by comparing the microscopic images before and after fusion caused by controllable heating. Stearic acid (SA) particles in irregular and spherical shape were selected as a typical excipient to demonstrate the methodology, which were identified from the mixed particles based upon its melting characteristics to detect their particle sizes as well as the size distributions. In the same approach, the morphology and particle size of fenofibrate particles as API in tablets were analyzed. The results illustrated that the particle diameters and particle size distributions of the selected components in the mixture of particles can be detected via the hot-melting characteristics under the prerequisite of proper pretreatment to separate selected components from other particles in microscopic field. In conclusion, this research provides a practical approach for the reverse engineering purpose to brand products and the consistent evaluation of generic drugs.