Exploring the mechanism of Huangjing pill in the treatment of Alzheimer’s disease based on network pharmacology and molecular docking

Objective To reveal the mechanism of Huangjing pill in treating Alzheimer’s disease(AD)based on network pharmacology and molecular docking technology.Methods We obtained the active ingredients and targets of Huangjing pill through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and supplemented the effective components by consulting literature and predicted targets through the PharmMapper database.We used DrugBank,the GeneCards,the TTD,and the OMIM database to collect targets of AD.The Venn diagram was drawn and the key targets of Huangjing pill in the treatment of AD were obtained by Venny 2.1 platform.The Cytoscape 3.8.1 software was used to construct a network diagram of“drugs-active ingredients-key targets-disease”.The protein-protein interaction(PPI)network diagram was constructed through the STRING 11.5 database.DAVID database was used for Gene Ontology function and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis.AutoDock Vina1.1.2 software was used for molecular docking of the active components and core targets,and PyMOL 1.7.2.1 software was used for visual processing.Results After screening,we obtained 13 active ingredients and 116 targets of Huangjing Pill,1438 related targets for AD,and 75 common targets.566 items by GO enrichment analysis and 149 items related to KEGG pathway enrichment were obtained.Molecular docking results showed that there is a strong affinity between the key active ingredients and the core targets.Conclusion This study revealed that Huangjing pill could treat AD through multiple components,multiple targets and multiple pathways.

The pharmacological mechanism and molecular details of Platycodon grandiflorum in the treatment of novel coronavirus Pneumonia(COVID-19)

Background:Novel coronavirus pneumonia(COVID-19)has developed as a pandemic of global concern.There is an urgent need to develop effective and safe therapies.Platycodon grandiflorum(PG),one of the most famous traditional Chinese herbs,may be satisfied.In this study,we explored the pharmacological mechanism of PG in the treatment of COVID-19.Method:The active compounds and potential targets were acquired from public databases.The protein-protein interaction,the Gene Ontology,and the Kyoto Encyclopedia of Genes and Genomes were determined through bioinformatics analysis.Molecular docking and molecular dynamics were performed to further verify the findings.Result:A total of 38 bioactive ingredients and 276 gene targets of PG were identified.There were 78 intersected targets of PG and COVID-19.The network analysis revealed that luteolin,Platycogenic acid A,Platycogenic acid C,Polygalacic acid,and acacetin may be candidate agents.The AKT1,VEGFA,TP53,MAPK3,TNF,IL6,CASP3,EGFR,STAT3,and CCND1 were the important potential drug targets.Gene Ontology terms are involved in biological processes,which are mainly concentrated in inorganic substances and apoptosis,etc.The Kyoto Encyclopedia of Genes and Genomes pathway was involved in several aspects,such as Virus infection and immune regulation-related pathways.Molecular docking results showed that compounds of PG are closely bound to related targets.Molecular dynamics further found that Robin,Flavplatycoside,and dimethyl 3-O-β-D-glucopyranosylplatycogenate A can maintain good stability and flexibility in the composite system.Conclusion:PG has multicomponent,multitarget,and multichannel characteristics,which can provide an important theoretical basis to treat patients with COVID-19.

Discovery of novel double pyrazole Schiff base derivatives as anti-tobacco mosaic virus(TMV) agents

Many pyrazole derivatives were reported to exhibit highly activity towards tobacco mosaic virus（TMV）.In this work,an optimized pyrazole Schiff base scaffold was designed and introduced to derive novel potential TMV inhibitors.Thirty-six compounds were synthesized,characterized by elemental analysis,mass spectra and nuclear magnetic resonance（NMR） spectroscopy and evaluated by biological experiments.The bioassay results showed that some of the synthesized compounds exhibited excellent anti-TMV activities.Especially,5-chloro-3-methyl-1H-pyrazole contained compound 4j showed ningnanmycin comparable inhibitory activity and can be considered as potential anti-TMV candidate agent.With molecular docking,compound 4j insert into nucleotide sequence（GAAGUU） of OriRNA stably which revealed nucleotide could be a target of these compounds.