Understanding Mechanisms of Sinomenine in Morphine Addiction Treatment Using Network Pharmacology and Molecular Docking Approaches
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Abstract
Introduction: Sinomenine, derived from Sinomenium acutum, has been reported as a potential treatment for morphine addiction but its mechanisms are poorly understood. Hence this study was conducted to investigate the potential mechanisms underlying sinomenine effects on morphine addiction. Materials and methods: Potential protein targets for sinomenine were predicted using SwissTarget Prediction and PharmMapper while morphine addiction targets were collected from DisGeNet and GeneCards databases. Protein-protein interaction was examined using GeneMANIA web server while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted using ShinyGO online tool. Topological network analysis was performed using Cytoscape to measure the degree centrality, betweenness centrality and closeness centrality values while molecular docking analysis was done using AutoDock Vina to determine the binding energies and interactions. Results: A total of 15 sinomenine targets were identified to be involved. Among the identified targets, 37.94% shared protein domains and 19.64% displayed physical interactions. Relevant biological processes, molecular functions, cellular components and signalling pathways were identified involving G-protein coupled opioid receptor signalling pathways and activities, integral component of presynaptic membrane and mitophagy. Molecular docking suggested that the substituted aromatic ring of sinomenine plays important roles in the binding to the protein targets. The top five most significant protein targets were identified based on the binding energies and degree centrality values, namely OPRD1, OPRK1, NOS1, OPRM1 and SRC. Conclusion: Sinomenine interacted with various protein targets and pathways which can potentially treat morphine addiction mainly via opioid receptors and their signalling pathways.
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