Evaluation of anti inflammatory activity of fucoidan isolated from sargassum wightii as dual COX LOX inhibitor

Abstract

Marine seaweed contains fucose-rich heteropolysaccharides called newlinefucoidans, noted for their diverse biological functions. Seaweed and sea newlinecucumbers are two marine sources of fucoidans, which are newlineheteropolysaccharides high in sulphated fucose. Fucoidan has piqued interest newlinedue to its distinct biological functions including its potential to manage newlineinflammatory diseases. By inhibiting COX and LOX enzymes can prevent newlinearachidonic acid metabolism shunting, thus avoiding gastric toxicity linked to newlineselective COX-2 inhibitors. newlineThis study investigates the anti-inflammatory effects of fucoidan newlinefrom Sargassum wightii on cyclooxygenase, lipoxygenase, nitric oxide, and newlinecarrageenan-induced paw edema. In LPS-stimulated RAW 264.7 macrophage newlinecells, fucoidan and diclofenac dual-inhibit COX and LOX enzymes, with IC50 newlinevalues of 44.03±3.74 µg/ml and 34.92±5.14 µg/ml for COX, and 28.26±2.06 newlineµg/ml and 26.54±1.37 µg/ml for LOX, respectively. Fucoidan reduces NO newlinelevels concentration-dependently, with IC50 values of 17.99±3.15 µg/ml for newlinediclofenac and 17.59±2.43 µg/ml for LPS-stimulated RAW264.7 cells. It also newlinesuppresses LPS-stimulated COX-2 and 5-LOX gene expression in RAW newline264.7 cells. Molecular docking studies show that fucoidan and diclofenac newlinehave more stable interactions with COX and LOX enzymes than arachidonic newlineacid, with binding energies from -7.0 to -8.5 Kcal/mol. The MD simulations newlineprovided detailed trajectories that were analyzed to determine the hydrogen newlinebond formation, radius of gyration, solvent accessible surface (SAS), root newlinemean-square fluctuation (RMSF), (Rg), and root-mean-square deviation newline(RMSD). These parameters indicated stable binding conformations and newlinedynamic behavior of Fucoidan within the active sites of the enzymes. newline