Exploration of mechanism of action of Armadillidium vulgare in the treat-ment of cancer pain based on network pharmacology and experimental validation
Objective To explore the mechanism of Armadillidium vulgare in the treatment of cancer pain by using network pharmacology and ani-mal experiments.Methods The chemical constituents of were obtained by searching relevant literatures from CNKI,Wanfang Data,and PubMed database,and the retrieval time was from the establishment of the database to December 2023.After the SMILES structure of each component was obtained by PubChem,SwissADME was further used for screening,and the drug target was predicted by SwissTarget Prediction platform.The can-cer pain target database was constructed from GeneCards database and mapped with the drug target of Armadillidium vulgare.The"drug-composi-tion-common target"and protein-protein interaction network was constructed,and network topology analysis and visualization with Cytoscape soft-ware were carried out;KEGG pathway enrichment analysis for targets and genes using the R-package clusterProfiler.Forty clean male C57BL/6 mice,aged 6-8 weeks and weighing 20-25 g,were selected.Of these,ten were set up as sham surgery group and 30 were moulded.The cancer pain model was constructed by injection of intratibial lung cancer cells.After successful modeling,they were divided into model group,high dose group(200 mg/kg)group,and low dose group(50 mg/kg),according to random number table method with ten in each group.Western blot assay was used to detect the protein expression of the selected key targets.Results A total of 483 mouse female targets,2 940 cancer pain targets,and 260 drug-disease common targets were identified.ALB,interleukin-6(IL-6),vascular endothelial growth factor A(VEGFA),mitogen-activated protein kinase(MAPK)3,EGFR,SRC,MAPK1,and ESR1 were selected as key genes,and these targets were mainly enriched in the PI3K-Akt signaling pathway.The levels of IL-6,VEGFA,MAPK3,and MAPK1 in the spinal cord of mice in the model group were higher than those in the sham opera-tion group,and the differences were statistically significant(P<0.05).The expression levels of IL-6,MAPK3,VEGFA,and MAPK1 in the spinal cord of high dose group were lower than those of model group,the differences were statistically significant(P<0.05).The expression levels of IL-6,MAPK3,and MAPK1 in the spinal cord of low-dose group were lower than those of model group,while the expression levels of VEGFA were higher than those of model group,the differences were statistically significant(P<0.05).The protein expression levels of IL-6,VEGFA,MAPK1 and MAPK3 in spinal cord of high dose group were lower than those of lowdose group,the differences were statistically significant(P<0.05).Conclu-sion The results of this study suggest that Armadillidium vulgare have analgesic effects on cancer pain in mice,and the mechanism may be related to inhibiting the abnormal increase of IL-6,MAPK3,VEGFA,and MAPK1 expression and regulating the PI3K/Akt signaling pathway.