02638nas a2200253 4500008004100000245012600041210006900167260001500236300001200251490000700263520182900270653002202099653002002121653002302141653002202164653001802186653001602204100003402220700002002254700001602274700002902290700002502319856004002344 2025 eng d00aAndrographolide and Resveratrol as Potential Modulators of AIM2 and IFI16 Inflammasomes in Periodontitis: A Docking Study0 aAndrographolide and Resveratrol as Potential Modulators of AIM2  cApril 2025 a179-1870 v173 a

Background: Proinflammatory cytokines play a critical role in the destruction of periodontal tissues. DNAsensing 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. Methods: 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. Results: 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. Conclusion: Molecular docking and dynamics analyses indicate that andrographolide demonstrates a stronger binding affinity to AIM2 and IFI16 inflammasomes compared to resveratrol. This suggests andrographolide as a promising host modulatory candidate for the therapeutic management of periodontitis.

10aAIM2 inflammasome10aAndrographolide10aIFI16 inflammasome10aMolecular docking10aPeriodontitis10aResveratrol1 aArunachalam, Lalitha, Tanjore1 aSuresh, Snophia1 aLavu, Vamsi1 aVedamanickam, Shankarram1 aNagarajan, Nissanthe uhttps://www.phcogj.com/article/2493