Hang Ma1, Feng Xu1,2, Chang Liu1, Navindra P Seeram1. 1. Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA. 2. College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, People's Republic of China.
Abstract
Introduction: 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.
Introduction: 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.
Authors: Simona Pisanti; Anna Maria Malfitano; Elena Ciaglia; Anna Lamberti; Roberta Ranieri; Gaia Cuomo; Mario Abate; Giorgio Faggiana; Maria Chiara Proto; Donatella Fiore; Chiara Laezza; Maurizio Bifulco Journal: Pharmacol Ther Date: 2017-02-22 Impact factor: 12.310