Effect and Mechanism of Phillyrin in the Treatment of Sepsis Based on Network Pharmacology and Experimental Validation
Objective:To investigate the mechanism of phillyrin in the treatment of sepsis.Methods:Network pharmacology was used to predict the potential targets of phillyrin in the treatment of sepsis.A "phillyrin-common target-disease" network was constructed to establish the protein-protein interaction (PPI) network of phillyrin in the treatment of sepsis.Enrichment analysis of Gene Ontology (GO) and Kyoto Encyclope-dia of Genes and Genomes (KEGG) pathways was performed on the potential targets to understand the possible biological processes and path-ways involved in the treatment of sepsis by phillyrin.Molecular docking was conducted to test the binding affinity between phillyrin and core genes.A sepsis rat model was established by intraperitoneal injection of lipopolysaccharide (LPS),followed by intervention with phillyrin.The anti-septic effect of phillyrin was detected using reverse transcription real-time quantitative polymerase chain reaction (RT-qPCR).Re-sults:Network pharmacology analysis revealed that the core genes involved in the treatment of sepsis by phillyrin were SRC,AKT1,RHOA,CASP3,and HSP90AA1.GO enrichment analysis showed that phillyrin mainly affected biological processes,such as protein hydrolysis,posi-tive regulation of cell migration,and negative regulation of apoptosis,molecular functions,such as serine-type endopeptidase activity,enzyme binding,and protein binding,and cellular components,such as extracellular vesicles,extracellular region,and plasma membrane,thereby exer-ting an anti-septic effect.The effect of phillyrin may be related to pathways such as the PI3K-AKT signaling pathway,IL-17 signaling path-way,Rap1 signaling pathway,diabetes complication AGE-RAGE signaling pathway,and lipid and atherosclerosis-related pathways.Molecular docking results showed that phillyrin had a good binding affinity with the aforementioned core targets.Animal experimental results showed that compared with the results in the normal control group,the mRNA expression of inflammatory factors TNF-α,IL-6,IL-1β,SRC,RHOA,CASP3,and HSP90AA1 in lung tissues of the model control group was significantly upregulated (P<0.01).Compared with the model control group,phillyrin at doses of 10,20,and 40 mg/kg significantly downregulated the mRNA expression of TNF-α,IL-6,IL-1β,SRC,RHOA,CASP3,and HSP90AA1 in lung tissues (P<0.05 or P<0.01).Conclusion:Network pharmacology was used to predict the core targets and signaling pathways of phillyrin in the treatment of sepsis,and relevant validation was conducted through in vivo experiments,providing a refer-ence basis for further exploration of the mechanism of phillyrin in the treatment of sepsis.
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