Reporting the Anti-neuroinflammatory Potential of Selected Spondias mombin Flavonoids through Network Pharmacology and Molecular Dynamics Simulations

Abstract

Abstract Introduction: Neuroinflammation plays a pivotal role in the development and progression of neurodegenerative diseases, with a complex interplay between immune responses and brain activity. Understanding this interaction is crucial for identifying therapeutic targets and developing effective treatments. Aim: This study aimed to explore the neuroprotective properties of flavonoid compounds from Spondias mombin against neuroinflammation using a comprehensive in-silico approach, including network pharmacology, molecular docking, and dynamic simulations. Materials & Methods: Active flavonoid ingredients from S. mombin were identified, and their potential protein targets were predicted through Network Pharmacology. Molecular docking was conducted to determine the binding affinities of these compounds to cyclooxygenase-2 and FYN kinase, prioritizing docking scores ≥ -8.0 kcal/mol. Molecular dynamic simulations (MDS) assessed the stability and interaction profiles of these ligand-protein complexes. Results: The docking studies highlighted cyclooxygenase-2 and FYN kinase as significant targets, with catechin and epicatechin displaying specificity towards FYN. However, these compounds failed the blood-brain barrier permeability test. MDS confirmed the stability of catechin and a reference ligand at the FYN active site, with notable interactions involving hydrogen bonds, hydrophobic contacts, and water bridges. GLU54 emerged as a key residue in the catechin-FYN complex due to its prolonged hydrogen bond interaction stability. Conclusion: The findings underscore the potential of S. mombin flavonoids as therapeutic agents against neuroinflammation, though optimization and nanotechnology-based delivery methods are suggested to enhance drug efficacy and overcome blood-brain barrier limitations.