Proinflammatory cytokines play a critical role in the destruction of periodontal tissues. DNA-sensing inflammasomes, such as AIM2 and IFI16, are key mediators in the secretion of IL-1 and IL-18 and facilitate pyroptosis in periodontitis. Andrographolide and resveratrol are phytocompounds known for their anti-inflammatory effects, though their precise mechanisms of action remain uncertain. This study aimed to elucidate the molecular interactions of andrographolide and resveratrol with AIM2 and IFI16 inflammasomes using a computational approach. Ten phytocompounds were selected and analyzed via molecular docking. Protein-ligand docking was conducted with AutoDock 4.2.6. Binding affinities and hydrogen bond interactions were assessed. Andrographolide and resveratrol complexes with AIM2 and IFI16 were further subjected to 100 ns molecular dynamics simulations using GROMACS software to assess complex stability. Both andrographolide and resveratrol complexes demonstrated stability throughout the simulations, with adequate inter-hydrogen bonding. Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) analysis revealed that AIM2-andrographolide (-112.100 ± 18.106 kJ/mol) and IFI16-andrographolide (-50.047 ± 27.076 kJ/mol) complexes exhibited higher binding energies compared to AIM2-resveratrol (-15.328 ± 2.539 kJ/mol) and IFI16-resveratrol (-12.534 ± 20.184 kJ/mol) complexes. The results indicate that andrographolide demonstrates a stronger binding affinity to AIM2 and IFI16 inflammasomes compared to resveratrol. This suggests andrographolide is a promising host modulatory candidate for the therapeutic management of periodontitis.
