夏桑菊防治干眼症的网络药理学机制及实验验证OACSTPCD

The study was to explore the mechanism of action of Xiasangju in the treatment of xeroph-thalmia by using network pharmacology,molecular docking method and cell experiments.The chemical components of Xiasangju were analyzed by ultra-fast high performance liquid chromatography tandem triple quadrupole time-of-flight mass spectrometry(UFLC-Triple-TOF-MS/MS).Targets of active components were predicted and disease related targets were retrieved with the help of network pharma-cologic database and analysis platform.The network was built using cytoscape software and STRING platform.GO and KEGG pathway enrichment analysis was performed using the DAVID database,and the top 4 key targets were matched with their corresponding active component molecules.A hypertonic model of dry eye was constructed in vitro to verify the core target.A total of 61 chemical components were identified,and 24 effective components potentially related to xerophthalmia were selected for further screening.These 24 components were found to interact with 315 potential target proteins.Among them,the key active components of Xiasangju were identified as rosmarinic acid,linarin and chlorogenic acid,which targeted TNF-α,Caspase1,IL-6,and IL-1β.Enrichment analysis revealed that the therapeutic targets of Xiasangju for xerophthalmia were concentrated in multiple biological pro-cesses,including the AGE-RAGE signaling pathway,TNF signaling pathway,and others.In cell ex-periments,these three active components not only significantly inhibited cell viability reduction but al-so enhanced the migration ability of high osmolarity-induced corneal epithelial cells.They effectively suppressed the expression of Caspase1 and IL-1β genes,as well as the secretion level of TNF-α protein in high osmolarity-induced human corneal epithelial cells.The main active components,rosmarinic acid,linarin and chlorogenic acid,in Xiasangju exerted protective and reparative effects on human cor-neal epithelial cells under high osmolarity conditions.They reduced the protein level of TNF-α and the relative expression of Caspase1 and IL-1β mRNA.