Predicting Pharmacological Mechanism of Multiple Trace Elements in Preterm Low Birth Weight Infants Based on Network Pharmacology

OBJECTIVE To explore the pharmacological mechanism of trace elements in preterm low birth weight infants through network pharmacology. METHODS Targets associated with trace elements were obtained from Drugbank database and TTD database. Genes related to preterm low birth weight infants were collected from GeneCards database and DisGeNET database. Two groups of data were intersected to get mapping targets. Protein-protein interaction network of mapping targets were constructed by STRING database. Candidate targets were screened by Cytoscape 3.6.1 and ranked to obtain key targets. The major trace elements were defined by establishing network of “trace elements-candidate targets”. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) term enrichment analysis was performed via g:Profiler software to predict the molecular mechanisms and related pathways of trace elements on preterm low birth weight infants. RESULTS A sum of 211 targets of trace elements in preterm low birth weight infants were screened, including 26 candidate targets and three key targets: albumin(ALB), glyceraldehyde-3-phosphate dehydrogenase(GAPDH) and fibronectin 1(FN1). The major trace elements were copper(Cu) and zinc(Zn), regulating 22 and 19 targets respectively. KEGG pathway enrichment analysis predicted that three major pathways were complement and coagulation cascades, cholesterol metabolism as well as lipid and atherosclerosis. CONCLUSION The major trace elements Cu and Zn may cause neuronal damage and reduce the risk of oxidative stress-related diseases in premature infants through the regulation of GAPDH, ceruloplasmin(CP), superoxide dismutase 1(SOD1), etc. The appropriate levels of Cu and Zn for preterm infants may regulate cholesterol metabolism and other signaling pathways and therefore reduce the risk of cardiovascular diseases in premature infants and adult. Further investigation of the pharmacological mechanism of trace elements in preterm infants is necessary to provide a more sufficient theoretical basis for the good growth and development of preterm infants.