Multi-target mechanism of Naoshuantong capsule for treatment of Ischemic stroke based on network pharmacology and molecular docking.

BACKGROUND: Naoshuantong capsule (NST capsule) is a classic Chinese patent medicine, which can treat ischemic stroke (IS) and has good clinical efficacy. However, its pharmacological mechanism remains to be further explored in the treatment of IS. METHODS: The bio-active components and potential targets of NST Capsules were obtained by ETCM and TCMSP databases. In addition, the related targets of IS were collected by Genecard, OMIM, DrugBank, TTD and DisGeNET databases. NST-IS common target was obtained by Venn platform. PPI network of NST-IS common target and the composition - target network diagram of NST Capsule were constructed by Cytoscape3.8.1. Finally, AutoDock was used for molecular docking. RESULTS: 265 targets were predicted from 32 active compounds in NST Capsule, 109 common targets were identified between NST Capsule and IS. The top 10 key targets of PPI network were ALB, TNF, TP53, VEGFA, CASP3, MYC, etc. Enrichment analysis showed that NST capsules treated IS mainly through lipid and atherosclerosis, fluid shear stress and atherosclerosis signaling pathways. CONCLUSION: Through the methods of network pharmacology and molecular docking, this study clarified that NST capsules play a role in the treatment of IS, which is multi-target, multi-channel and multi-component regulation. This study further explored the pharmacological mechanism of NST capsule in the treatment of IS, which can provide some references for the subsequent research in the pharmacological mechanism of NST capsule.

Compound musk injection in the treatment of ischemic stroke: A network analysis of the mechanism of action.

BACKGROUND: Ischemic stroke (IS) is affected by a wide range of factors and has certain treatment limitations. Studies have reported that compound musk injection (CMI) is effective in the treatment of IS, however, its mechanism of action is still unclear. METHODS: The main active ingredients in CMI were retrieved from HERB, TCMSP and BATMAN databases, and the relevant targets were predicted by Swiss Target Prediction platform. MalaCards, OMIM, DrugBank, DisGeNET, Genecards and TTD databases were used to obtain the genes related to IS. The intersection of drugs and disease targets was used to construct protein-protein interaction networks, and gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. AutoDock Vina software was used for molecular docking, and cell experiments were conducted to verify the results. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression level of relative mRNA in cells. RESULTS: Network analysis and molecular docking results showed that the key targets of CMI in the treatment of IS were SRC, TP53, PIK3R1, MAPK3, PIK3CA, MAPK1, etc. KEGG pathway enrichment analysis mainly involved PI3K/Akt signaling pathway, Rap1 signaling pathway and MAPK signaling pathway. The molecular docking results all showed that the key ingredients were strong binding activity with the key targets. The quantitative RT-PCR results indicated that CMI may increase the expression of PIK3CA, MAPK3 mRNA and decrease the expression of SRC mRNA. CONCLUSIONS: CMI can treat IS by regulating pathways and targets related to inflammatory response and apoptosis in a multi-component manner.

Based on network pharmacology and molecular docking to predict the mechanism of TMDZ capsule in the treatment of IS.

BACKGROUND: Ischemic stroke (IS) is the most common cardiovascular and cerebrovascular disease in clinic. Qiangli Tianma Duzhong Capsule (TMDZ capsule) has significant therapeutic effect to IS. Therefore, it is great significance to explore the mechanism of action of TMDZ capsules in the treatment of IS. METHODS: The potential active components and possible targets of TMDZ capsule were obtained from TCMSP and The Encyclopedia of Traditional Chinese Medicine databases. IS related targets were collected by Genecard database, OMIM database, TTD database and DisGeNET database. The common target network of drug-diseases was constructed using Cytoscape for visualization analysis. Potential mechanisms were identified through enrichment analysis of gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Three key targets (ALB, TNF, and INS) were selected from the key networks with high correlation scores in PPI for molecular docking, through molecular docking, the interaction between target and protein is visualized. RESULTS: 59 active components and 648 targets of TMDZ capsules and 2286 targets of IS were obtained through database mining. Compound-target network is constructed with 117 nodes and 1185 edges. GO and KEGG suggest that lipids and atherosclerosis, fluid shear forces and atherosclerosis, neurodegenerative pathways - multiple diseases and blood circulation play important roles in the treatment of IS. CONCLUSIONS: This study reveals the molecular mechanism of TMDZ capsules in the treatment of IS by integrating molecular docking with a network pharmacological strategy, which not only confirmed the clinical efficacy of TMDZ capsule, but also laid the foundation for further experimental research.

[Fertility and Environmental Impacts of Urban Scattered Human Feces Used as Organic Granular Fertilizer for Leaf Vegetables].

The disposal of urban scattered human feces has become a difficult problem for the management of modern city. In present study, the scattered human feces underwent the collection, scum removal, flocculation and dehydration, finally became the granular fertilizer; the effects of the ratio of fertilizer to soil on the growth of the pakchoi and the quality of soil and leaching water were evaluated, and the feasibility of granular fertilizer manuring the pakchoi was discussed by pot experiments. The results showed that the granular fertilizer significantly enhanced the production of the pakchoi which were not polluted by the intestinal microorganisms under the experiment conditions; meanwhile, at the proper ratio of fertilizer to soil, the concentration of these microorganisms in the leaching water was lower than that in the control check. Chemical analyses of soil revealed that the nutrient content of nitrogen, phosphorus, potassium and organic matters in soil became much richer in all treatments. In addition, the granular fertilizer improved the physical- chemical properties of soil, including raising the level of soil porosity and reducing the volume weight of soil. Application of granular fertilizer won't pollute the soil or leaching water; instead, it can also prevent nitrogen, potassium and intestinal microorganisms from leaching inio ground water at the proper ratio of granular fertilizer to soil.

Efficacy of trans-cinnamaldehyde against Psoroptes cuniculi in vitro.

The acaricidal activity of trans-cinnamaldehyde was evaluated in vitro on Psoroptes cuniculi. In this study, different concentrations of trans-cinnamaldehyde were tested, and the observed mites mortality was compared with that observed in untreated and treated (Acacerulen R®) controls. The morphological changes in P. cuniculi treated with trans-cinnamaldehyde were examined with light microscopy. By the analysis of variance one-way test, up to 8 µg/ml of trans-cinnamaldehyde gave highly significant (P < 0.01) percentages of mite mortality compared with the untreated controls, but only up to 256 µg/ml, it showed the same efficacy of Acacerulen R®. At the same time, a bioassay was conducted by exposing mites to varying doses of trans-cinnamaldehyde in vitro cultures. The resulting data were analyzed by using a time-dose-mortality modeling technique, yielding the parameters for time and dose effects of P. cuniculi. The ß value was 2.01, indicating that trans-cinnamaldehyde had a good activity to kill P. cuniculi adults. Based on the time-dose-mortality relationships fitted and the virulence indices estimated, trans-cinnamaldehyde is a promising microbial agent for mites control.

Transcriptional and functional analysis shows sodium houttuyfonate-mediated inhibition of autolysis in Staphylococcus aureus.

Sodium houttuyfonate (SH), an addition compound of sodium bisulfite and houttuynin, showed in vitro antibacterial activity against 21 Staphylococcus aureus (S. aureus) strains grown in planktonic cultures. Microarray results showed decreased levels of autolysin atl, sle1, cidA and lytN transcripts in the SH-treated strain as compared to the control strain, consistent with the induction of the autolytic repressors lrgAB and sarA and with the downregulation of the positive regulators agrA and RNAIII. Triton X-100-induced autolysis was significantly decreased by SH in S. aureus ATCC 25923, and quantitative bacteriolytic assays and zymographic analysis demonstrated SH-mediated reduction of extracellular murein hydrolase activity in these cells. Anti-biofilm assay showed that SH is poorly active against S. aureus grown in biofilm cultures, whereas SH diminished the amounts of extracellular DNA (eDNA) of S. aureus in a dose-dependent manner, which suggested that SH may impede biofilm formation by reducing the expression of cidA to inhibit autolysis and eDNA release in the early phase. Some of the microarray results were confirmed by real-time RT-PCR.