Therapeutic targets and signaling mechanisms of vitamin C activity against sepsis: a bioinformatics study

Abstract

Sepsis is a life-threatening complication of pneumonia, including coronavirus disease-2019 (COVID-19)-induced pneumonia. Evidence of the benefits of vitamin C (VC) for the treatment of sepsis is accumulating. However, data revealing the targets and molecular mechanisms of VC action against sepsis are limited. In this report, a bioinformatics analysis of network pharmacology was conducted to demonstrate screening targets, biological functions, and the signaling pathways of VC action against sepsis. As shown in network assays, 63 primary causal targets for the VC action against sepsis were identified from the data, and four optimal core targets for the VC action against sepsis were identified. These core targets were epidermal growth factor receptor (EGFR), mitogen-activated protein kinase-1 (MAPK1), proto-oncogene c (JUN), and signal transducer and activator of transcription-3 (STAT3). In addition, all biological processes (including a top 20) and signaling pathways (including a top 20) potentially involved in the VC action against sepsis were identified. The hub genes potentially involved in the VC action against sepsis and interlaced networks from the Kyoto Encyclopedia of Genes and Genomes Mapper assays were highlighted. Considering all the bioinformatic findings, we conclude that VC antisepsis effects are mechanistically and pharmacologically implicated with suppression of immune dysfunction-related and inflammation-associated functional processes and other signaling pathways. These primary predictive biotargets may potentially be used to treat sepsis in future clinical practice.

Targets of Vitamin C With Therapeutic Potential for Cardiovascular Disease and Underlying Mechanisms: A Study of Network Pharmacology

“…In agreement with GO analysis, KEGG pathway enrichment analysis also showed that the therapeutic effects of vitamin C on CVD were mainly associated with the JAK-STAT signaling pathway, as well as the PD-1 pathway, EGFR tyrosine kinase inhibitor resistance, the FoxO signaling pathway, and the chemokines signaling pathway ( Li et al, 2020a ; Li et al, 2020b ). There is crosstalk among STAT, PD-1, EGFR, and FoxO signals.…”

Overview of the possible role of vitamin C in management of COVID-19

“…In addition, vitamin C deficiency in critically ill patients is associated with increased vasopressor requirements, multi-organ failure and increased mortality [ 69 ]. Vitamin C has an anti-sepsis effect by reducing inflammatory response and oxidative stress as well as suppressing immunological dysfunction, which are the main pathophysiological mechanisms of sepsis [ 70 ]. Pre-clinical evidence showed that vitamin C supresses excessive cytokine release leading to sepsis-induced organ dysfunction [ 67 ].…”

Circular RNA circFADS2 is Overexpressed in Sepsis and Suppresses LPS-Induced Lung Cell Apoptosis by Inhibiting the Maturation of miR-15a-5p

“…Sepsis is essential a type of in ammatory disease, in which the involvement of multiple players is required [7,8]. With the increased elucidation of the molecular mechanism of sepsis, some molecular factors, such as ALK, have been proven to be potential targets for the development of novel therapies against sepsis and sepsis-induced organ failures, such as targeted therapy to treat sepsis by regulating regulated gene expression [9,10]. However, to date, effective targets for sepsis targeted therapy remain lacking.…”