Abstract
Complications due to influenza are often associated with inflammation with excessive release of cytokines. The bulbs of Fritillariae thunbergii (FT) have been traditionally used to control airway inflammatory diseases, such as bronchitis and pneumonia. To elucidate active compounds, the targets, and underlying mechanisms of FT for the treatment of influenza-induced inflammation, systems biology was employed. Active compounds of FT were identified through the TCMSP database according to oral bioavailability (OB) and drug-likeness (DL) criteria. Other pharmacokinetic parameters, Caco-2 permeability (Caco-2), and drug half-life (HL) were also identified. Biological targets of FT were retrieved from DrugBank and STITCH databases, and target genes associated with influenza, lung, and spleen inflammation were collected from DisGeNET and NCBI databases. Compound-disease-target (C-D-T) networks were constructed and merged using Cytoscape. Target genes retrieved from the C-D-T network were further analyzed with GO enrichment and KEGG pathway analysis. In our network, GO and KEGG results yielded two compounds (beta-sitosterol (BS) and pelargonidin (PG)), targets (PTGS1 (COX-1) and PTGS2 (COX-2)), and pathways (nitric oxide, TNF) were involved in the inhibitory effects of FT on influenza-associated inflammation. We retrieved the binding affinity of each ligand-target, and found that PG and COX-1 showed the strongest binding affinity among four binding results using a molecular docking method. We identified the potential compounds and targets of FT against influenza and suggest that FT is an immunomodulatory therapy for influenza-associated inflammation.
Highlights
Seasonal influenza A virus (IAV) is an infectious RNA virus that causes acute respiratory infection, leading to high morbidity and mortality during pandemics [1]
We identified the potential compounds and targets of Fritillariae thunbergii (FT) against influenza and suggest that FT is an immunomodulatory therapy for influenza-associated inflammation
Compounds that satisfied oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18 criteria suggested by the Traditional Chinese Medicine Systems Pharmacology database (TCMSP) database were considered potent [14]
Summary
Seasonal influenza A virus (IAV) is an infectious RNA virus that causes acute respiratory infection, leading to high morbidity and mortality during pandemics [1]. Due to complex matrices of plant extracts, elucidation of the underlying molecular mechanisms is difficult because of the synergistic effects of the active compounds and multiple therapeutic targets involved. The technique uses compound-disease-target network visualization to evaluate multi-target mechanisms of plant extracts [8,9,10,11]. Computational research is another promising time-saving alternative to experimental research that may aid in identification of novel compounds and targets [12,13]. In an attempt to understand the molecular mechanism of action of FT against influenza-associated inflammation, three compound-disease-target (C-D-T) networks (influenza, lung inflammation, and spleen inflammation) were constructed and merged into a single network to yield an influenza-associated inflammation network system.
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