Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, Rhode Island, USA.
College of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, People's Republic of China.
Cannabis Cannabinoid Res. 2021 Aug;6(4):288-299. doi: 10.1089/can.2020.0025. Epub 2020 Jul 1.
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. 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. 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. 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.
已发表的临床前和临床研究支持 CBD 的抗炎活性，但参与其作用机制的分子靶点（例如基因和蛋白质）仍不清楚。在此，进行了基于网络的药理学分析，以帮助确定 CBD 抗炎活性的潜在分子靶点。靶基因和蛋白质从多个在线数据库中获得，包括 Swiss target prediction、Online Mendelian Inheritance in Man 和 DrugBank 数据库。使用 Cytoscape 工具构建化合物-靶标-疾病网络，使用 Search Tool for the Retrieval of Interacting Genes/Proteins 数据库建立蛋白质-蛋白质相互作用网络。从化合物-靶标-疾病网络中鉴定出的先导蛋白通过计算对接进一步研究其与 CBD 的相互作用。此外，使用基因本体富集和京都基因与基因组百科全书分析鉴定 CBD 抗炎活性涉及的生物学途径。鉴定出一组蛋白质，包括细胞肿瘤抗原 p53、NF-kappa-B 必需调节剂、肿瘤坏死因子（TNF）受体、转录因子 p65、NF-kappa-B p105、NF-kappa-B 抑制剂 alpha、NF-kappa-B 激酶亚单位 alpha 抑制剂和表皮生长因子受体，作为 CBD 抗炎活性的先导靶点。分子对接进一步证实了这一发现，表明先导蛋白与 CBD 之间存在相互作用。此外，还鉴定了几种信号通路，包括 TNF、Toll 样受体、丝裂原激活蛋白激酶、核因子 kappa-B 轻链增强子的激活 B 细胞和核苷酸结合寡聚化结构域样受体，作为 CBD 抗炎活性中介的关键调节剂。基于网络的药理学分析确定了 CBD 抗炎活性的潜在分子靶点和信号通路。这项研究的结果增加了越来越多的数据支持将 CBD 用作有前途的抗炎天然产物。
