Computational evaluation of walnut oil phytoconstituents as modulators of lipoxygenase and cyclooxygenase in inflammation resolution

Inflammation is a crucialrnevent for initiating tissue repair and regeneration following injury, canrnbecome detrimental when dysregulated, often progressing into chronicrninflammation. Recent studies have emphasized that the resolution ofrninflammation is an active, regulated process mediated by SpecializedrnPro-resolving Mediators (SPMs) derived from omega-3 and omega -6rnpolyunsaturated fatty acids (PUFAs). This study focusses on the potential ofrnWalnut (Juglans regia L.) seed phytoconstituents to modulate key enzymes involved inrninflammation resolution such as, 5-lipoxygenase (5-LOX), 12-LOX, 15-LOX, andrncyclooxygenase-2 (COX-2), through in-silico molecular docking analysis.rnNine phytoconstituents from walnut seed, including retinol, ascorbic acid,rnlinolenic acid, and linoleic acid, were evaluated for their physicochemical andrnpharmacokinetic properties using SwissADME and docked with inflammation-resolvingrnenzymes using AutoDock Vina and results were visualized using Biovia Discoveryrnstudio. Retinol demonstrated the strongest binding affinity, particularly withrn5-LOX and 12-LOX, while linolenic and linoleic acids showed consistentrninteractions across all targets. Most compounds exhibited favourablerndrug-likeness and high gastrointestinal absorption, with some capable ofrncrossing the blood-brain barrier, highlighting their therapeutic potentialrnagainst neural inflammation. From this study, it can be hypothesised that,rnwalnut phytochemicals by serving as precursors to SPMs and exhibitingrnfavourable interaction profiles with key enzymatic targets, may representrnpromising agents for the dietary management and therapeutic modulation ofrninflammation, ultimately aiding in the prevention of chronic inflammatoryrndiseases.