In silico Investigation of the Anti-inflammatory Potential of Ligands from Commonly Used Spices, Herbs and Medicinal Plants

Introduction: Inflammation has been shown to be implicated in many communicable and noncommunicable diseases. Several studies have indicated the beneficial/protective effects of phytochemicals from many commonly used herbs, spices, vegetables and medicinal plants against ailments that have inflammatory components. Our study investigated the possible anti-inflammatory properties of ligands from these commonly used plants by exploring their interactions with the cyclooxygenase-2 enzyme, using bioinformatics techniques. Cyclooxygenase-2 (COX-2) is a key enzyme involved in the production of prostaglandins implicated in inflammatory disorders.

Materials and Methods: Twenty-eight ligands from plants were used for the study; ibuprofen and celecoxib served as reference ligands. The 3-D structures of the 30 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 and subjected to molecular docking through standard bioinformatics procedures. One of the ligands (quercetin) was further subjected to molecular dynamics simulation using the Desmond Maestro software.

Results: Many of the ligands compared very well with celecoxib in their binding properties and exhibited more negative binding energies than ibuprofen. Additional interactions of H bonds and hydrophobic bonds were noticed post molecular dynamics simulation of quercetin with COX-2, indicating dynamic forces fluctuations. MD simulations showed that Gln42, Gly45, Pro 153, Pro154 and Glu465 were the best amino acid side chains that interacted with quercetin for the stabilization of the protein-ligand complex. The energy values and protein-ligand interactions indicate affinity and stability of complex.

Conclusion: Many of the ligands subjected to molecular docking and MD simulation can be taken as promising drug targets 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 of both selective and nonselective NSAIDs. In addition, the authors, through the findings of this study, recommend more consumption of natural foods that have health benefits rather than processed and artificial products.