Pro-angiogenic VEGF inhibition by cadaverine and hydrocinnamic acid metabolites: impairment of periodontal regeneration due to periodontal inflammation.

Abstract

Background: Cadaverine and hydrocinnamic acid are frequent metabolites in inflamed periodontal areas. Their role as a metabolite for plant growth inhibition has been established, but their relevance in humans has yet to be determined. Moreover, Vascular endothelial growth factor (VGEF) is a consistent growth factor in neo-angiogenesis in periodontal regeneration. The aim of the study was to utilize an in-silico approach to investigate the potential interaction between Cadaverine and hydrocinnamic acid, metabolites found in inflamed periodontal areas, and vascular endothelial growth factor (VEGF), with a focus on understanding their role in periodontal regeneration.

Methods: Desmond MD simulation is an efficient technique for analyzing the dynamics of protein-ligand complexes. The system is minimized and equilibrated after the protein-ligand combination has been solvated in a water box. The system is simulated for a desired time, typically 10-100 nanoseconds. The simulation data is examined to reveal the interactions between proteins and ligands, such as binding affinities, contact maps, and hydrogen bonding patterns. VEGF interactome of metabolites was assessed.

Results: Docking interactions between hydrocinnamic acid and VEGF with binding energy -5.0 kcal/mol and docking interactions between Cadaverine and VEGF with -3.6 kcal/mol. Fluctuations in RMSD values remain within 2.0 for the simulation duration, which is perfectly fine. Ligand RMSD values fluctuated within 1.0 Angstrom up to 25 ns, flipped in ligand mode, regained equilibrium at 80 ns, and remained steady for the simulation duration.

Conclusions: The current in-silico study suggests that metabolites like Cadaverine and hydrocinnamic acid, which are produced during periodontal inflammation, may have the ability to block pro-angiogenic vascular endothelial growth factors. This interference can have notable effects on the healing and regeneration of tissues by preventing the formation of blood vessels and the expression of VEGF.