Open AccessA Network Pharmacology Approach to Identify Potential Molecular Targets for Cannabidiol's Anti-Inflammatory Activity
Author(s) -
Hang Ma,
Xu Feng,
Chang Liu,
Navindra P. Seeram
Publication year - 2021
Publication title -
cannabis and cannabinoid research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.156
H-Index - 17
eISSN - 2578-5125
pISSN - 2378-8763
DOI - 10.1089/can.2020.0025
Subject(s) - drugbank , biology , transcription factor , computational biology , gene , genetics , pharmacology , drug
Published preclinical and clinical studies support the anti-inflammatory activity of CBD, but the molecular targets (e.g., genes and proteins) that are involved in its mechanisms of action remain unclear. Herein, a network-based pharmacology analysis was performed to aid in the identification of potential molecular targets for CBD's anti-inflammatory activity. Materials and Methods: Target genes and proteins were obtained from several online databases, including Swiss target prediction, Online Mendelian Inheritance in Man, and the DrugBank database. A compound-target-disease network was constructed with Cytoscape tool, and a network of protein-protein interactions was established with the Search Tool for the Retrieval of Interacting Genes/Proteins database. Lead proteins identified from the compound-target-disease network were further studied for their interactions with CBD by computational docking. In addition, biological pathways involved in CBD's anti-inflammatory activity were identified with the Gene Ontology enrichment and the Kyoto Encyclopedia of Genes and Genomes analysis. Results: A panel of proteins, including cellular tumor antigen p53, NF-kappa-B essential modulator, tumor necrosis factor (TNF) receptor, transcription factor p65, NF-kappa-B p105, NF-kappa-B inhibitor alpha, inhibitor of nuclear factor kappa-B kinase subunit alpha, and epidermal growth factor receptor, were identified as lead targets involved in CBD's anti-inflammatory activity. This finding was further supported by molecular docking, which showed interactions between the lead proteins and CBD. In addition, several signaling pathways, including TNF, toll-like receptor, mitogen-activated protein kinases, nuclear factor kappa-light-chain-enhancer of activated B cells, and nucleotide-binding oligomerization domain-like receptors, were identified as key regulators in the mediation of CBD's anti-inflammatory activity. Conclusion: A network-based pharmacology analysis identified potential molecular targets and signaling pathways for CBD's anti-inflammatory activity. Findings from this study add to the growing body of data supporting the utilization of CBD as a promising anti-inflammatory natural product.