基于数据挖掘和网络药理学探讨中药复方治疗围绝经期干眼的用药规律及作用机制OA

OBJECTIVE To explore the medication patterns of Chinese medicine compounds in treating perimenopausal dry eye disease(PDED)and screen out the core medicines,and to analyze the mechanism of action of the core medicines through network pharmacology.METHODS Chinese literature was retrieved from the China National Knowledge Infrastructure,Wanfang Data Knowledge Service Platform,and VIP Chinese Journal Service Platform up to November 2024.Chinese medicine prescriptions used clinically were screened and organized according to inclusion and exclusion criteria.The Traditional Chinese Medicine Inheritance Computing Platform V3.5 software was used to analyze medicine frequency,efficacy,property-flavor and meridian tropism,association rules,and clustering to determine the core Chinese medicines for treating PDED.The TCMSP database was utilized to screen active ingredients and target proteins of the core medicines.PDED-related targets were obtained from the GeneCard and OMIM databases.The STRING and Cytoscape databases were used to construct a protein-protein interaction(PPI)network,and Cytoscape was used to build a"core medicines-active ingredients-intersection targets"network.Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were performed using Metascape.Molecular docking analysis was conducted using PubChem and RCSB databases to validate the binding activity of core components with key targets.RESULTS(1)Literature data mining:A total of 45 articles were included,comprising 50 prescriptions involving 104 Chinese medicines.Among the medicine properties,cold nature was the most frequent(261 times,43.50％).Among the flavors,sweet was the most frequent(438 times,48.72％).Regarding meridian tropism,the liver meridian was the most frequent(338 times,21.45％).(2)High-frequency medicine analysis:Thirty medicines with a usage frequency≥six times(high-frequency medicines)were identified.The top three were Lycii fructus(Gouqizi,34 times,68.00％),Poria(Fuling,32 times,64.00％),and Angelicae Sinensis radix(Danggui,30 times,60.00％).The top three categories of high-frequency medicines by total frequency were tonifying-deficiency medicines(259 times,56.80％),heat-clearing medicines(87 times,19.08％),and dampness-dispelling diuretic medicines(51 times,11.18％).(3)Association rule and cluster analysis:The top three highly associated medicine pairs were"Chrysanthemi flos-Lycii fructus","Paeoniae radix alba-Angelicae sinensis radix",and"Rehmanniae radix praeparata-Lycii fructus".Three groups of core medicine combinations were obtained.The main effect of group Ⅰ was nourishing the liver and kidney,clearing liver fire;Group Ⅱ was tonifying kidney Yang and nourishing Yin to purge fire;Group Ⅲ was nourishing Yin and blood,promoting fluid production and moistening dryness.(4)Network pharmacology analysis:A total of 87 active ingredients and 513 action targets were collected for the core medicines.311 PDED-related targets were obtained,with 55 being intersection targets with the core medicine active ingredients.PPI network analysis identified key targets such as IL-6,TNF,IL1B,ESR1,and TP53.The"core medicines-active ingredients-intersection targets"network revealed that quercetin,kaempferol,β-sitosterol,etc.,were closely related to the treatment of PDED.GO functional enrichment analysis indicated that the biological processes of core medicines in treating PDED mainly involved steroid metabolism,epithelial cell proliferation,response to lipopolysaccharide,inflammatory response,etc.KEGG pathway enrichment analysis involved 126 pathways,mainly including AGE-RAGE,IL-17,HIF-1 signaling pathways,etc.Molecular docking showed four pairs with good binding activity:Quercetin-AR,quercetin-ESR1,β-sitosterol-PGR,and quercetin-PPARG.CONCLUSIONS Poria,Lycii fructus,Rehmanniae radix praeparata,Moutan cortex and Chrysanthemi flos are the core medicines for clinically treating PDED,which may exert therapeutic effects through multiple components,targets,and pathways.