Abstract
Background There are still controversies about the curative effect of vitamin C in treating HIE, and its mechanism of action is not entirely clear. This study is designed to explore the potential molecular mechanism of vitamin C in treating neonatal hypoxic ischemic encephalopathy (HIE). Methods The effect targets of vitamin C and the pathogenic targets of neonatal HIE were obtained via retrieval of public databases to screen out the molecular targets of vitamin C acting on neonatal HIE. Gene Ontology (GO) functional annotations and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the main targets. Vitamin C and the optimum target structural components are subjected to molecular docking and molecular dynamics simulation analysis via computer software so as to verify their binding activity and stability. Result Based on 16 overlapping targets of vitamin C and HIE, seven main targets were identified in this study. According to GO and KEGG analysis, molecular functions (top 25 items) and signal pathways (21 items) related to inflammatory reaction, immune response, and cell transcriptional control may be potential pathways for vitamin C to treat neonatal HIE. Molecular docking and molecular dynamics simulation were adopted to definitively determine the 4 optimum core target spots. Conclusion The efficacy of vitamin C on HIE is involved in the immunoregulation and inflammation-related functional processes and signal pathways. These molecular mechanisms, including core targets, will contribute to the clinical practice of neonatal HIE in the future.
Highlights
Hypoxic ischemic encephalopathy (HIE) is a brain damage caused by asphyxia at birth, as well as one of the most common causes of neonatal death and long-term disability, occurring in 2 to 3 per 1000 newborns [1]
Detailed Data of Targets. e HIE related genes of newborns were screened through the DisGeNET database; screening criteria: gene-disease association score >0.1; the HIE of newborns was screened through the GeneCards database; screening criteria: gene score >1.805; genes related to neonatal HIE were determined with the above criteria
protein-protein interaction (PPI) data related to the function of these 16 targets were collected via the STRING database, and a PPI network related to the pharmacological targets and functions of vitamin C on neonatal HIE was constructed (Figure 1(b))
Summary
Hypoxic ischemic encephalopathy (HIE) is a brain damage caused by asphyxia at birth, as well as one of the most common causes of neonatal death and long-term disability, occurring in 2 to 3 per 1000 newborns [1]. The pathological and biochemical changes of neonatal hypoxic-ischemic brain damage are a cascade process, with nerve cell apoptosis or necrosis being the final result of brain damage [4]. Many studies have shown that the central nervous system will produce large amounts of oxygen radicals and inflammatory mediators that promote nerve cell necrosis and apoptosis in the hours following an hypoxic ischemic brain damage and during brain reperfusion and reoxygenation [5, 6]. Some in vitro studies have found that intervention in the early inflammatory phase of hypoxic ischemic brain damage can protect neurons to reduce the degree of brain damage [8, 9]
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