Network pharmacology and molecular docking-based study on the antiinflammatory and antioxidant mechanisms of morindolide

Global mortality and morbidity are high due to inflammatory diseases such as rheumatoid arthritis, cardiovascular disease and cancer. Pharmacological treatments that target specific molecules or pathways may not adequately address the complexity and multifactorial. By studying complex biological networks and discovering various therapeutic targets, network pharmacology offers a possible alternative. Network pharmacology may facilitate the design of targeted therapies and enhance therapeutic outcomes by identifying drug-target interactions and signalling pathways. Morindolide is a bioactive iridoid compound isolated and identified from the tuber of Myrmecodia platytyrea, a plant traditionally used to treat cancer and other inflammation-related diseases in Southeast Asia. Previous studies suggest that morindolide exhibits anti-inflammatory and antioxidant properties, reinforcing its potential as a lead compound for therapeutic development. Thus, this study employed network pharmacology and molecular docking to identify the mechanisms underlying these effects. Morindolide's target genes were identified using SymMap, Swiss Target Prediction and PharmMapper databases. Anti-inflammatory and antioxidant-related genes were retrieved from the GeneCards database. Common targets were identified through Venn analysis. A protein-protein interaction (PPI) network was constructed using STRING and Cytoscape to identify hub genes. GO function and KEGG pathway analyses were performed using DAVID and ShinyGO. Molecular docking between morindolide and hub proteins was conducted using AutoDock and visualised with LigPlot. The analysis revealed 56 common targets between morindolide and anti-inflammatory/antioxidant effects. Seven hub genes were identified as PTGS2, IL1B, MMP2, HSP90AA1, NOS2, PLA2GA and CYP2E1. GO analysis revealed morindolide's involvement in inflammatory responses, nitric oxide biosynthesis, and response to lipopolysaccharide. KEGG analysis highlighted pathways in cancer, arachidonic acid metabolism, IL-17 signalling and neurodegeneration. Molecular docking confirmed stable binding between morindolide and hub proteins, with binding energies ranging from -5.19 to - 6.62 kcal/mol. Significant interactions were observed with CYP2E1 (-6.62 kcal/mol), MMP2 (-6.6 kcal/mol), and NOS2 (-6.24 kcal/mol). This study successfully identified the potential targets, biological processes and signalling pathways involved in morindolide's anti-inflammatory and antioxidant effects by utilising network pharmacology and molecular docking techniques. The findings provide a robust theoretical foundation for future experimental research, ultimately paving the way for developing novel therapeutic strategies and potential clinical applications of morindolide in treating inflammation-related disorders.