Objective:To explore the potential mechanism of hepatotoxicity induced by Nux Vomica through network toxicology.Methods:The active components and targets of Nux Vomica were identified and screened by Traditional Chine...Objective:To explore the potential mechanism of hepatotoxicity induced by Nux Vomica through network toxicology.Methods:The active components and targets of Nux Vomica were identified and screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database(TCMSP),literature research,PubChem Database,Swiss Target Prediction database,etc.Genecards,pharmGKB and OMIM databases were used to collect hepatotoxicity related targets,then,cross them with active component targets to obtain potential targets of hepatotoxicity caused by Nux Vomica.A"Nux Vomica-Potential active components-Potential targets-Hepatotoxicity"network was constructed with Cytoscape 3.8.0 software.The String 11.0 database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted by R software,and then the obtained pathways directly related to hepatotoxicity were integrated.Results:In this study,37 active components were screened via TCMSP and literature research,468 targets for the active components of Nux Vomica were obtained.There were 533 hepatotoxicity-related targets,73 potential targets for hepatotoxicity caused by Nux Vomica,and 26 potential active components,among which Ferulic acid,Novacine,Icajine,Simiarenol were the key active components for hepatotoxicity caused by Nux Vomica,and JUN,RELA,and STAT3 were the core target proteins of hepatotoxicity caused by Nux Vomica.There were 1859 GO entries(P-value<0.05),including 1709 entries of Biological Process(BP),39 entries of Cellular Component(CC),and 111 entries of Molecular Function(MF).KEGG enrichment analysis revealed 145 pathways(value<0.05),of which PI3K/AKT signaling pathway,HIF-1 signaling pathway,EGFR tyrosine kinase inhibitor resistance were strongly correlated with the hepatotoxicity caused by Nux Vomica.Conclusion:Through network toxicology analysis,it was found that lots of potential components in Nux Vomica may be involved in the activation of the excessive inflammatory response,oxidative stress,and the LPS response through multiple targets and multiple pathways,resulting in the generation of hepatotoxicity.展开更多
To explore the effect of particle size on the quality uniformity and in vitro release performance of Strychnos nux-vomica powder, seven samples of Strychnos nux-vomica powder with different particle sizes were prepare...To explore the effect of particle size on the quality uniformity and in vitro release performance of Strychnos nux-vomica powder, seven samples of Strychnos nux-vomica powder with different particle sizes were prepared.Microstructures and particle sizes were analyzed, and high performance liquid chromatography(HPLC) was used to test the contents and in vitro release performances of brucine and strychnine in the samples. Results showed that the contents and the in vitro release rates of brucine(or strychnine) in different samples were different since there are different proportions of endosperms to epidermal cells in Strychnos nux-vomica powder with different particle sizes. Brucine and strychnine in each sample were promptly released in the first ten minutes and their cumulative release rates were higher than 70% after ten minutes. Eighty minutes later, the cumulative release rate tended to be a constant. Considering the quality uniformity and safety of Strychnos nux-vomica powder used as traditional Chinese medicine, it would be better to control the particle size of Strychnos nux-vomica powder between 100 and 140 mesh in which the maximum cumulative release rate in vitro of brucine and strychnine can be relatively low within this range.展开更多
文摘Objective:To explore the potential mechanism of hepatotoxicity induced by Nux Vomica through network toxicology.Methods:The active components and targets of Nux Vomica were identified and screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database(TCMSP),literature research,PubChem Database,Swiss Target Prediction database,etc.Genecards,pharmGKB and OMIM databases were used to collect hepatotoxicity related targets,then,cross them with active component targets to obtain potential targets of hepatotoxicity caused by Nux Vomica.A"Nux Vomica-Potential active components-Potential targets-Hepatotoxicity"network was constructed with Cytoscape 3.8.0 software.The String 11.0 database was used to construct the protein-protein interaction(PPI)network of the targets and to screen out the core targets.In addition,Gene Ontology(GO)function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted by R software,and then the obtained pathways directly related to hepatotoxicity were integrated.Results:In this study,37 active components were screened via TCMSP and literature research,468 targets for the active components of Nux Vomica were obtained.There were 533 hepatotoxicity-related targets,73 potential targets for hepatotoxicity caused by Nux Vomica,and 26 potential active components,among which Ferulic acid,Novacine,Icajine,Simiarenol were the key active components for hepatotoxicity caused by Nux Vomica,and JUN,RELA,and STAT3 were the core target proteins of hepatotoxicity caused by Nux Vomica.There were 1859 GO entries(P-value<0.05),including 1709 entries of Biological Process(BP),39 entries of Cellular Component(CC),and 111 entries of Molecular Function(MF).KEGG enrichment analysis revealed 145 pathways(value<0.05),of which PI3K/AKT signaling pathway,HIF-1 signaling pathway,EGFR tyrosine kinase inhibitor resistance were strongly correlated with the hepatotoxicity caused by Nux Vomica.Conclusion:Through network toxicology analysis,it was found that lots of potential components in Nux Vomica may be involved in the activation of the excessive inflammatory response,oxidative stress,and the LPS response through multiple targets and multiple pathways,resulting in the generation of hepatotoxicity.
基金Supported by the Plan Issue of Shanghai Science &Technology Committee(No.13401901100)
文摘To explore the effect of particle size on the quality uniformity and in vitro release performance of Strychnos nux-vomica powder, seven samples of Strychnos nux-vomica powder with different particle sizes were prepared.Microstructures and particle sizes were analyzed, and high performance liquid chromatography(HPLC) was used to test the contents and in vitro release performances of brucine and strychnine in the samples. Results showed that the contents and the in vitro release rates of brucine(or strychnine) in different samples were different since there are different proportions of endosperms to epidermal cells in Strychnos nux-vomica powder with different particle sizes. Brucine and strychnine in each sample were promptly released in the first ten minutes and their cumulative release rates were higher than 70% after ten minutes. Eighty minutes later, the cumulative release rate tended to be a constant. Considering the quality uniformity and safety of Strychnos nux-vomica powder used as traditional Chinese medicine, it would be better to control the particle size of Strychnos nux-vomica powder between 100 and 140 mesh in which the maximum cumulative release rate in vitro of brucine and strychnine can be relatively low within this range.
