Elucidating the Anti-Inflammatory Properties of Garcinia kola and Vernonia amygdalina through in silico Molecular Biology Techniques

Introduction: Inflammation is implicated in many disorders, including communicable and noncommunicable diseases. Cyclooxygenase-2 (Cox-2) is a key enzyme involved in the production of prostaglandins implicated in inflammatory disorders.  Garcinia kola and Vernonia amygdalina are medicinal plants being used for treating various ailments in many parts of the world and extensive in vitro and in vivo studies have been conducted on them. Five phytochemicals were selected from the two plants; aspirin and celecoxib were used as reference drugs. This study investigated the interactions of the seven ligands with the Cox-2 enzyme, using in silico molecular biology techniques. Materials and Methods: The 3-D structures of the seven ligands were retrieved from the PubChem database in their Structure Data Format (SDF). Cox-2 was retrieved in its Protein Data Bank (PDB) format. The ligands and the protein were converted to their pdbqt formats through the open babel software. The Cox-2 was docked with the ligands using the Auto-Dock Vina software. The binding energies and the root mean square deviation values were noted. Pharmacophore modeling was visualized by using the Biovia Discovery Studio Visualizer. One of the ligands (luteolin) was further subjected to molecular dynamics simulation using the desmond maestro software. Results: While celecoxib had the best binding property with Cox-2 (-10.8 kcal/mol, 3 H bonds), the five ligands from the two plants had better binding properties than aspirin (which had -6.5kcal/mol, 1 H bond). Kolaviron, from G. kola (-9.1 kcal/mol, 3 H bonds) and luteolin, from V. amygdalina (-8.5kcal/mol, 2 H bonds) demonstrated the best binding properties among the five phytochemicals. Additional interactions of H bonds and hydrophobic bonds were noticed post molecular dynamics simulation of luteolin with Cox-2, indicating dynamic forces’ fluctuations. MD simulations showed that Ser530 and Tyr385 were the best amino acid side chains that interacted with luteolin for the stabilization of the protein-ligand complex. Conclusion: The energy values and protein-ligand interactions indicate affinity and stability of the complex. Luteolin can be taken as a promising drug target and subjected to ADMET (absorption, distribution, metabolism, excretion, toxicity) properties analysis and clinical trials. This is especially important in view of the various side effects associated with both nonselective and selective Cox-2 inhibitors, including aspirin and celecoxib.