Identifying Active Compounds and Targets of Fritillariae thunbergii against Influenza-Associated Inflammation by Network Pharmacology Analysis and Molecular Docking

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.

Beneficial effect of Indigo Naturalis on acute lung injury induced by influenza A virus

“…NO produced by inducible nitric oxide synthetase (iNOS) is an important proin ammatory mediator. NO has direct antiviral properties against some viruses, whereas during virus infections NO can mediate immunopathology and/or inhibit the antiviral immune response to promote chronic infection [44]. Accumulated evidence suggests that NO and oxygen radicals such as superoxide are key molecules in the pathogenesis of various infectious diseases and accelerate tissue damage [45].…”

Based on network pharmacology and molecular docking to explore the Traditional Chinese Medicine anti-influenza mechanisms:Chinese protocol for diagnosis and treatment of influenza.

“…With the rapid development of bioinformatics, network pharmacology has become a new way to effectively reveal the molecular and pharmacological mechanisms of TCM formulae, and it will also become a new paradigm for TCM research [3][4][5][6][7]. The network pharmacological studies on the anti-influenza effects of compound Artemisia annua, Jingyin granule and Reduning injection have been carried out [8][9][10].…”

Systematically Deciphering the Pharmacological Mechanism of Fructus Aurantii via Network Pharmacology

“…The candidate ingredients of FA were retrieved from the TCMSP database. Identification of ADME (absorption, distribution, metabolism, and excretion) properties from the TCMSP database was employed to screen the candidate compounds in FA [ 11 , 18 , 19 ]. Currently, DL evaluation (e.g., Lipinski's Rule-of-Five, Opera's rules of DL, and the ROES filter) is integrated into computational drug design/discovery pipelines [ 20 ].…”

“…Herbs contain numerous compounds and complexes and can target many macromolecules, which present a tremendous challenge in conventional pharmacological research. Thus, network pharmacology, an emerging field that integrates computer-aided drug design and bioinformatic analysis, has been rapidly developed to reveal the complex interactions between bioactive ingredients and their related targets [ 11 , 12 ]. It is a novel and promising method that systematically investigates the interaction networks of compounds, targets, pathways, and diseases to elucidate the potential underlying therapeutic mechanisms of TCM [ 13 ].…”