ABSTRACT
Objective:To explore the molecular mechanism of Lycii Fructus and Salviae Miltiorrhizae Radix et Rhizoma (FLRSM) in the treatment of retinitis pigmentosa (RP) based on network pharmacology and bioinformatics. Method:Possible intake active components and targets of FLRSM were screened out and predicted by traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP). Gene targets related to RP were mined through disease gene databases. Protein-protein interaction (PPI) network of component-targets and disease-targets were mapped by functional protein association networks (STRING), and the intersection of the two networks was obtained. The gene ontology and kyoto encyclopedia of genes and genomes(KEGG) pathway of the intersection network were analyzed by the database for annotation, visualization and integrated discovery(DAVID). CytoHubba analysis was used to screen out the key targets. Result:A total of 390 active ingredients related to FLRSM were retrieved from TCMSP. According to pharmacokinetic parameters, 110 active ingredients were screened out, 19 active ingredients were further screened out, and 208 targets related to these constituents were retrieved. Totally 206 genes directly related to RP were obtained from the disease gene databases. And 79 genes were obtained from the intersection of PPI networks of component targets and disease targets. These genes mainly involved in biological processes, such as protein autophosphorylation, transcriptional regulation and cell proliferation, and the molecular functions mainly involved adenosine triphosphate binding, transcription factor activity, core promoter binding, and were enriched in nuclear, transcription factor complex, nucleus, cytoplasm and other regions. It was mainly related to neurotrophin signaling pathway, cell cycle related pathway and Wnt signaling pathway. And 8 key gene targets for FLRSM treatment of RP were identified by further screening. Conclusion:The material basis of pharmacodynamic action of FLRSM involves 19 active ingredients, such as porous sterol and tanshinone ⅡA. The key targets of FLRSM in the treatment of RP include 8 genes, such as E2F transcription factor 1(E2F1) and retinoblastoma gene1(RB1).The main mechanism is related to the regulation of neurotrophin signaling pathways, cell cycle related pathways and other signaling networks.
ABSTRACT
AIM:To remark the effect of Qingguang'an Ⅱ on expression of PAX6, Ngn1, and Ngn2 mRNA of rats with chronic high intraocular pressure.METHODS:Totally 40 male SD rats were randomly divided into 6 groups, that was:A:blank group, B:model group, C:Qingguang'an Ⅱ low dose group, D:Qingguang'an Ⅱ moderate dose group, E:Qingguang'an Ⅱ high dose group, F:Yimaikang disket group.B, C, D, E, F groups of experimental rats were established the model of chronic high intraocular pressure (IOP) by cauterizing of superficial scleral vein.Animal model was established successfully by using monitoring IOP consistently keep above 25mmHg for 8wk as cut-off criterion.Tissues of Eyes were obtained after intragastric administration for 2wk and 4wk.The expressions of PAX6, Ngn1, and Ngn2 mRNA were investigated by Real-time PCR.RESULTS:At the time-point of 2wk, PAX6, Ngn1, and Ngn2 mRNA in group B were statistically expressed in lower level comparing with other groups (P0.05).CONCLUSION:In summar, Qingguang'an Ⅱ and Yimaikang disket can remarkably increase the expressions of PAX6, Ngn1, and Ngn2, which suggest protecting the optic nerve of rats caused by chronic high IOP.What's more, this study indicated that, in the protection of optic nerve of rats with chronic high IOP, the high dose of Qingguang'an Ⅱ at the time-point of 4wk was the better choice.