Mechanisms of Vitamin C Regulating Immune and Inflammation Associated with Neonatal Hypoxic-Ischemic Encephalopathy Based on Network Pharmacology and Molecular Simulation Technology

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.

Vitamin C as A Possible Immunity Booster

“…It is possible that vitamin C can cure newborn HIE by influencing inflammation, the immunological response, and cellular transcriptional regulation. Since this is the case, vitamin C is likely one of the primary medications used to treat HIE [13]. This study suggests a possible treatment by Vitamin C through certain pathways.…”

The Role of Vitamin C in Preventing Some Neurodegenerative Diseases: Alzheimer’s, Parkinson’s, and Huntington’s

“…VC plays a crucial role in the synthesis of catecholamines, carnitine, cholesterol, amino acids, and certain peptide hormones. Additionally, it acts as a cofactor in numerous important enzymatic reactions [6,7,10]. One of the well-known functions of VC is its involvement in the hydroxylation of lysine and proline residues during collagen synthesis.…”

“…VC is found in millimolar concentrations in neurons [2,4,6], hence it serves as a "micronutrient" in the central nervous system (CNS) [4,6,10]. VC is most abundant in the hippocampus, cerebral cortex, and amygdala [8].…”

“…The neuroprotective function of VC stems from its ability to attenuate neurotoxicity [2,3]. VC safeguards neurons against oxidative stress, promotes their differentiation and maturation, and regulates the synthesis or release of neuroregulatory factors such as serotonin, catecholamines, and glutamate [10,12,18]. In a study on VC deficiency, a decrease of up to 1% in plasma and liver, and up to 30% in brain cells compared to the control group was observed [18].…”

“…Long-term VC intake has been reported to significantly reduce amyloid plaque formation [3]. VC supplementation as an adjuvant therapy has gained significant interest in individuals with AD and Parkinson's disease (PH) [10]. Alzheimer's patients have reported low plasma levels of VC, which are associated with increased oxidative stress [1].…”