Plants have traditionally served as a rich reservoir of medicinal compounds, yet numerous species remain underexplored in terms of their chemical composition and pharmacological properties. While many Atriplex species have undergone extensive examination, A. leucoclada, a halophyte endemic to the deserts of Saudi Arabia, has not been thoroughly assessed for its secondary metabolites or therapeutic capabilities. The present research evaluated the chemical profile and anti-inflammatory effects of A. leucoclada. The dried aerial portions of the plant were first treated with n-hexane to remove lipids, after which the residue was extracted using 80% methanol. The n-hexane fraction (ATH) underwent GC–MS analysis, whereas the methanol fraction (ATD) was fractionated through various chromatographic techniques to yield primary natural products. Structural determination of the isolated compounds relied on spectroscopic approaches, incorporating sophisticated NMR methods. The in vitro inhibitory effects of both fractions on COX-1 and COX-2 were assessed. In silico docking of the characterized molecules into the binding pockets of COX-1 (PDB: 6Y3C) and COX-2 (PDB: 5IKV) was performed.
Chemical analysis of the ATD fraction resulted in the isolation and characterization of nine compounds. Notably, with the exception of 20-hydroxy ecdysone (1), all were documented for the first time in A. leucoclada, and luteolin (6) as well as pallidol (8) represent novel findings within the Atriplex genus. Both ATD and ATH demonstrated dose-dependent inhibition of COX-1 and COX-2, with IC50 values of 41.22 and 14.40 μg/ml for ATD, and 16.74 and 5.96 μg/ml for ATH, respectively. Selectivity ratios were calculated as 2.86 for ATD and 2.80 for ATH, compared to 2.56 for Ibuprofen, suggesting preferable inhibition of COX-2. Docking simulations corroborated the experimental data, showing binding energies from -9 to -6.4 kcal/mol and -8.5 to -6.6 kcal/mol for the isolated compounds against COX-1 and COX-2, respectively; similarly, compounds detected via GC–MS exhibited values from -8.9 to -5.5 kcal/mol and -8.3 to -5.1 kcal/mol, versus Ibuprofen's -6.9 and -7.5 kcal/mol. Most compounds displayed strong affinities, with interaction modes varying according to structural features. These findings position A. leucoclada as a promising reservoir of anti-inflammatory natural products.
