Structural Basis of Anthocyanin-Mediated Modulation of IL-2, IL-17, and TNF-α: A Docking and Molecular Dynamics Study

Anthocyanins are naturally occurring flavonoid pigments widely distributed in plants and are recognized for their antioxidant and anti-inflammatory activities. However, the molecular mechanisms underlying their potential immunomodulatory effects remain poorly characterized, particularly regarding their direct interactions with key signaling cytokines. In this study, a set of selected anthocyanins was investigated using a hierarchical computational workflow targeting three major pro-inflammatory cytokines: interleukin-2 (IL-2), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α). Molecular docking analyses identified primulin and antirrhinin as the most favorable binders, forming stabilizing hydrogen bonds and hydrophobic interactions within predicted cytokine interaction interfaces. To further assess the stability of these complexes, molecular dynamics simulations were performed under near-physiological conditions. Trajectory analyses demonstrated stable ligand-protein interactions and persistent intermolecular contacts throughout the 100 ns simulation period. These findings provide molecular-level insights into anthocyanin-cytokine interactions and highlight their potential relevance for modulating inflammatory signaling pathways.