NEUROPROTECTIVE POTENTIAL OF CHICORY (CICHORIUM INTYBUS) PHYTOCHEMICALS: GSK-3β INHIBITION AND CALCIUM MODULATION VIA IN SILICO APPROACHES

Abstract

This research explores the efficacy of phytocompounds isolated from chicory (Cichorium intybus) to inhibit Glycogen Synthase Kinase 3 beta (GSK-3β), an important regulator of neurogenesis and Wnt/β-catenin signaling, by employing molecular docking simulations. GSK-3β dysregulation has been implicated in Alzheimer's disease, and for this reason, it is a promising drug target. Docking results showed high binding affinities of chosen compounds with chicoric acid having the best score (-10.2 kcal/mol) as it forms multiple hydrogen bonds with active site residues. High docking score (-9.1 kcal/mol) was also displayed by cichoricin, which indicates that the complex formation will be stable with GSK-3β as it contains a rich network of hydrogen bonding. Luteolin and esculetin also showed moderate binding but still maintained promise as competitive inhibitors. In addition to inhibition of GSK-3β, the molecules possessed calcium-binding affinity through functional groups such as carboxyl and hydroxyl moieties. Chicoric acid and cichoricin, specifically, exerted significant calcium-chelating activity, implicated in sustaining calcium homeostasis and averting excitotoxicity. The mechanism of action of these phytocompounds in inhibiting GSK-3β could potentially restore Wnt signaling, ensure neuronal survival, and augment cognition. Their ability to modulate intracellular calcium further attests to their neuroprotective role. Structural analyses validated stable interactions within the ATP-binding pocket of GSK-3β, reinforcing their therapeutic significance in neurodegenerative disease.