Study on the Mechanism of Action of Radix Angelica Sinensis and Radix Hedysari Ultrafiltration on Radiation-induced Heart Disease Based on Network Pharmacology and Experimental Verification
Objective To investigate the potential mechanism of Radix Angelica Sinensis and Radix Hedysari Ultrafiltration(RAS-RH)in the prevention and treatment of Radiation-induced Heart Disease(RIHD)based on network pharmacology and animal experiments.Methods The active components and predicted intervention targets of"Angelica sinensis-Radix Hedysari"were selected using the database of Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCM-SP).Retrieve RIHD target proteins in GeneCards and Human Mendelian Inheritance Database(OMIM),use R software to in-tegrate common targets,use STRING database to construct drug component-disease intersection target protein interaction net-work(PPI),and use R software to compare PPI results Perform visual analysis;use R software and Bioconductor platform to conduct Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of compo-nent-disease intersection targets.Forty male Wistar rats were randomly divided into blank group,model group,traditional Chi-nese medicine group,and western medicine group.Except for the blank group,the other groups were induced by X-ray(10Gy)single radiation to establish the RIHD rat model,and the rats were kept for 30 days.After 4 weeks of administration,ELISA was used to detect serum levels of troponin Ⅰ and brain natriuretic peptide in each group after 4 weeks of administration,and Western Blot detected the predicted core target caspase-3.The expression of interleukin(IL)-6 and human epidermal growth factor receptor(EGFR)in myocardial tissue of rats in each group.Results Network pharmacology analysis:RAS-RH had 16 main active components,210 corresponding targets,and 58 drug-disease intersection targets;GO enriched 1792 items(P<0.05),of which 1559 were biological processes(BP).38 items,cellular component(CC),95 molecular function(MF)items;KEGG pathway enrichment analysis screened out a total of 135 signaling pathways(P<0.05),mainly involving oncogen-ic-receptor activation signaling pathway,lipid Plasma and atherosclerosis signaling pathways,fluid shear stress and atheroscle-rosis,proteoglycans in cancer,phosphatidylinositol 3-kinase(PI3K)/Akt(protein kinase B),tumor necrosis factor(TNF),hypoxia-inducible factor(HIF)-1 and other signaling pathways.Animal experiments:The results of ELISA showed that the serum cTnⅠ and BNP of the rats in the model group were significantly increased,and compared with the model group,the cTnⅠ and BNP of the drug group were significantly decreased(P<0.05).-3.The expression of IL-6 protein was increased,and the expression of EGFR protein was decreased.Compared with the model group,Caspase-3 and IL-6 in the drug group were decreased,and the expression of EGFR protein was increased(P<0.05).Conclusion The effective components of Radix Angel-ica Sinensis and Radix Hedysari Ultrafiltration mainly regulate PI3K/Akt,TNF,HIF-1 and other signaling pathways by acting on core targets such as HIF-1α,MYC,Caspase-3,EGFR,IL-6,CCND1,and VEGFA.In this way,it can play the role of protecting RIHD and pass certain reference for the research on anti-radiation of traditional Chinese medicine.
network pharmacologyexperimental verificationRadix Angelica Sinensis and Radix Hedysari Ultrafiltrationradiation-induced heart diseasemechanism of action