INTEGRATED NETWORK PHARMACOLOGY, MOLECULAR DOCKING, AND IN-VITRO VALIDATION REVEAL POTENTIAL NOOTROPIC PHYTOCONSTITUENTS FROM SELECTED INDIAN MEDICINAL PLANTS AGAINST COGNITIVE IMPAIRMENT

Abstract

Cognitive impairment, a progressive neurodegenerative condition including dementia and Alzheimer’s disease that poses a significant global health challenge. Current therapeutic strategies primarily offer symptomatic relief and fail to arrest effective disease progression, underscoring the need for novel multi-target therapeutic approaches. The present study was planned to evaluate potential nootropic phytoconstituents from Allium cepa, Curcuma longa, and Coleus forskohlii, through integrated network pharmacology, molecular docking, and in-vitro validation studies. Network pharmacology study identified the PI3K-Akt signaling pathway as a central neuroprotective mechanism, along with EGFR, ErbB, estrogen, prolactin, and HIF-1 signaling pathways involved in neuronal survival, synaptic plasticity, and cognitive function. Molecular docking study revealed strong binding affinities of curcumin, quercetin, and rosmarinic acid towards key protein targets including AKT1, BCL2, EGFR, STAT3, and SRC. In-vitro validation revealed significant antioxidant and anti-inflammatory activities of curcumin, quercetin, and rosmarinic acid, supporting their therapeutic potential for the treatment of cognitive impairment. The integrated computational and experimental findings indicate that these phytoconstituents may modulate multiple pathological processes associated with cognitive impairment, including oxidative stress, neuroinflammation, apoptosis, and amyloid-related pathways. The findings suggest that curcumin, quercetin, and rosmarinic acid are promising multi-target nootropic phytoconstituents with therapeutic potential for the treatment of cognitive impairment.