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.

Vitamin C (VC), a well-reported antioxidant, is found with beneficial actions of preventing and treating pneumonia.

Background: Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation and ulcers in the digestive tract. Approximately 3 million US adults suffer from this disease. Mesalazine, an anti-inflammatory agent, is commonly used for the treatment of UC. However, some studies have demonstrated side effects of mesalazine, such as acute pancreatitis and hypereosinophilia. Therefore, a better understanding of the anti-inflammatory mechanism of mesalazine in UC could help improve the effectiveness of the drug and reduce its side effects. In this study, we used a dextran sodium sulfate-induced UC mouse model, and applied network pharmacology and omics bioinformatics approaches to uncover the potential pharmaceutical targets and the anti-inflammatory mechanism of mesalazine. Results: Network pharmacology analysis identified the core targets of mesalazine, biological processes, and cell signaling related to immunity and inflammatory responses mediated by mesalazine. Molecular docking analysis then indicated possible binding motifs on the core targets (including TNF-α, PTGS2, IL-1β, and EGFR). Metabolomics and 16S metagenomic analyses highlighted the correlation between gut microbiota and metabolite changes caused by mesalazine in the UC model. Conclusions: Collectively, the omics and bioinformatics approaches and the experimental data unveiled the detailed molecular mechanisms of mesalazine in UC treatment, functional regulation of the gut immune system, and reduction of intestinal inflammation. More importantly, the identified core targets could be targeted for the treatment of UC.