MOLECULAR BASIS OF ANTI-INFLAMMATORY POTENTIAL OF BIOACTIVE COMPOUNDS IN FERMENTED-CHICKPEA PUREES

Background: Literature data show that controlled fermentation enhance biological properties of legumes by reducing anti-nutritional compounds and improving digestibility and nutrient absorption. Moreover, legume fermentation may lead to the formation of antioxidant compounds (e.g. polyphenols) and bioactive peptides that could counteract oxidative stress and inflammatory processes in humans upon consumption. Computational techniques play crucial roles in in silico studies across fields, in understanding protein-ligand interactions and biomolecular structures and functions at atomistic level. Specifically, molecular docking explores protein-ligand binding affinity, while Molecular Dynamics simulations (MDs) provide insights into biomolecular behavior over time, essential process for understanding biological processes and drug mechanisms of action. Within the OnFoods project (www.onfoods.it), we are studying the functional potential of fermented chickpea purees by focusing on anti-inflammatory properties. In this study we aimed at elucidating the mechanism underpinning the anti-inflammatory effects of the bioactive components found in fermented chickpeas purees by using computational methodologies. Methods: The applied computational techniques included docking, MDs and trajectories analyses. The molecular mechanisms of chickpea-derived compounds against the pro-inflammatory target Nuclear Factor kappa B (NFkB) and Toll-like receptor 4 (TLR4) receptors were considered. Results: The binding modes of the bioactive fermented chickpea components retrieved from molecular docking calculations showed a good binding affinity. The most energetically stable binding conformations were submitter to MDs, and trajectory analyses confirmed the binding mode, providing a detailed understanding of the key interactions of such bioactive components, thus confirming their anti-inflammatory mechanism of action. Conclusions: In summary, through in silico analyses the results of this study shed light on the mechanisms underpinning the anti-inflammatory potential of chickpea upon consumption.