ABSTRACT
Objective To explore the potential targets and synergistic mechanisms of Kushen Decoction for the treatment of cryptosporidiosis using network pharmacology and molecular docking methods. Methods The main active ingredients of Kushen Decoction were captured from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TC-MSP) and the Universal Protein Resource (UniProt) database, and the potential targets were predicted. In addition, the active ingredients of Kushen Decoction that were not included in the TCMSP database were retrieved in CNKI, WanFang Data, CBM, PubMed and Web of Science databases, and the target genes of all supplemented active ingredients were predicted using the online TargetNet database. Network construction and analysis were performed using the Cytoscape software, and cryptosporidiosis-related targets were retrieved in the Comparative Toxicogenomics Database and GeneCards database. The protein-protein interaction (PPI) network was created using the STRING database, and the DAVID database was used for GO enrichment and KEGG pathway analyses. The tissue distribution of key targets was investigated using the BioGPS database, and the AutoDockTools software was employed to verify the molecular docking results. Results A total of 38 active ingredients of Kushen Decoction were screened, and the core ingredients included quercetin, (+)-14α-hydroxymatrine and apigenin. A total of 831 targets of Kushen Decoction and 512 cryptosporidiosis-related targets were predicted, and PPI network analysis revealed 69 key targets, including AKT1, TNF and IL-6. There were 303 biological processes, 46 molecular functions and 29 cellular components involved in the treatment of cryptosporidiosis with Kushen Decoction, and 13 KEGG pathways played a therapeutic role in the synergistic mechanisms of multiple targets, such as Toll-like receptor (TLR), nuclear factor kappa B(NF)-κB, nucleotide binding oligomerization domain like receptor (NLR) signal pathways. The core targets were mainly distributed in the hematologic and immune systems. Molecular docking analysis showed that the binding energy between active ingredients and key targets were all less than 0 kJ/mol, indicating the strong binding of ligands to receptors. Conclusions The active ingredients of Kushen Decoction, such as quercetin, (+)-14α-hydroxymatrine and apigenin, may act on targets like AKT1, TNF, IL-6 to modulate TLR, NLR and NF-κB signaling pathways to play a synergistic role in the treatment of cryptosporidiosis in the hematologic and immune system.
ABSTRACT
Objective: To optimize the forming process of gel patch and explore the compatibility-synergistic mechanism of Aconiti Radix-Zanthoxyli Pericarpium volatile oil gel patch. Methods: According to the indexes of skin followability, disclosing ability, initial adhesion and peeling degree, the substrate-property of eight commercially gel patches was evaluated. Then, with the comprehensive sensory evaluation, initial adhesion, stickiness and peeling degree as the index, single factor experiment and mixture design experiment were used to screen the proportion of matrix excipients of gel patch. Taking the number of acetic acid-induced writhing in mice as the index, the drug loading of gel paste was screened by in vivo animal evaluation. In addition, the compatibility effect of Aconiti Radix-Zanthoxyli Pericarpium volatile oil gel patch was studied by using formaldehyde-induced pain model and metabolomics. Results: Different brands of gel plaster had great difference in their skin followability, disclosing ability, initial adhesion and peeling degree. The initial adhesion and peel degree of gel patch had great influence on its disclosing ability and the greater the initial adhesion and peel degree were, the worse disclosing ability was. The matrix of the Aconiti Radix gel patch was 3% polyacrylic acid sodium NP700, 1.5% carboxymethyl cellulose sodium, 0.25% Carbomer, 0.06% crystalline aluminum chloride, 0.1% ethylenediamine tetra acetic acid two sodium, 26% glycerol, 61.5% water, 4% diatomaceous earth, 0.15% tartaric acid; Drug dosage of each gel patch was 560 mg extracts of Aconiti Radix. Zanthoxyli Pericarpium olatile oil could enhance the analgesic effect of Aconiti Radix gel patch, which might be mainly through glycerol phospholipid metabolism and linoleic acid metabolism. Conclusion: To ensure better adherence and disclosure of gel patch, the initial adhesive force of gel patch should be controlled between 7-18 balls and the peel degree should be controlled between 0.03-0.97 kN/m. The Prepared Aconiti Radix gel patch has a good appearance, adhesion and shape with a clear analgesic effect, and Zanthoxyli Pericarpium olatile oil can enhance analgesic effect of Aconiti Radix gel patch. This study provides a basis for the development and application of new preparations for the external use in Aconiti Radix.
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Objective To explore the cooperative mechanism of hospital research management and ethics review.Methods Through the analysis of current ethical conditions,as well as the relationship between hospital research management and ethical review,study on how to integrate them during the management of scientific research project.Results Research management and ethical review have different emphasis from different perspectives,however,both of them serve for research projects which makes inseparable connections.Conclusions Hospital research management and ethical review can be synergistic,according to which the management of scientific research projects will be more reasonable and scientific.
ABSTRACT
Synergistic effect is main pharmacological mechanism of traditional Chinese medicine(TCM). The research method based on the key targets combination is an important method to explore the synergistic effect of TCM. Peptide transporter 1 (PepT1) is an essential target for drug uptake into the bloodstream, accounting for about 50% of the total transporter protein content from the small intestine. Peroxisome proliferator-activated receptor α(PPARα) is the lipid-lowering target of fibrates, which have a good hypolipidemic effect by activating PPARα. It has been reported that PPARα could activate the gene expression of PepT1s, and PPARα agonists can promote the uptake of PepT1 substrates, indicating their synergistic effect. In this paper, PepT1 substrates and PPARα agonists from TCM were discovered, and their synergistic mechanism was also been discussed based on the target combination of PepT1 and PPARα. The support vector machine(SVM) model of PepT1 substrates was first constructed and utilized to predict potential TCM components. Meanwhile, merged pharmacophore and docking model of PPARα agonists was used to screen the potential active ingredients from TCM. According to the analysis results of two groups, the TCM combination of Panax notoginseng and Ganoderma lucidum, as well as TCM combination of P. notoginseng and Salvia miltiorrhiza were identified to have the synergistic mechanism based on target combination of PepT1 and PPARα. In this study, synergistic mechanism of TCM was analyzed for absorption and hypolipidemic effect based on target combination, which provides a new way to explore the synergetic mechanism of TCM related to pharmacokinetics.