Phytochemicals from <i>Aralia armata</i> as potential tumor necrosis factor-alpha inhibitors: A computational study

Molecular docking and molecular dynamics simulations were employed to screen plant-derived compounds from Aralia armata for potential inhibition of tumor necrosis factor-alpha (PDB ID: 2AZ5). Aralia armata has a history of use in traditional medicine and contains bioactive compounds with anti-inflammatory potential, such as triterpene glycosides, as reported in previous studies. The docking protocol was validated using root mean square deviation, yielding a value of 1.827 Å, confirming its reliability. The binding affinity analysis revealed that compounds calenduloside E ( 1 ), calenduloside G ( 7 ), calenduloside G methyl ester ( 8 ), and 3 β -( β -glucopyranosyloxy) olean-12-en-28-oic acid ( 38 ) exhibited the strongest interactions with tumor necrosis factor-alpha, with Tyr B:119 playing a critical stabilizing role. Molecular dynamics simulations demonstrated overall structural stability, with compound 8 exhibiting the lowest binding free energy, surpassing the reference inhibitor SPD304. Absorption, distribution, metabolism, excretion, and toxicity analysis indicated varying pharmacokinetic properties, with compound 8 showing the most balanced absorption, metabolism, and toxicity profile, whereas compound 7 exhibited potential toxicity concerns. These findings suggest that compound 8 is a promising candidate for further in vitro and in vivo validation as a tumor necrosis factor-alpha inhibitor.