Garcinol as A Promising Therapeutic Candidate for Alzheimer's Disease: Integrated Computational and In Vitro Target Analysis

Abstract Garcinol (GL) exhibits profound antioxidant and anti‐inflammatory properties, contributing to its promising neuroprotective action. Recent reports disseminate the capacity of GL to influence neuronal growth and survival, altering the neurochemical status in the brain and regulating memory and cognition. Thus, the concomitant neuro‐rescue property of garcinol may render it an effective therapeutics in Alzheimer's disease (AD). Emerging data relating histone acetylation abnormalities to the course of neurodegenerative disorders provides an effective basis to explore GL as an anti‐AD therapeutic. The present study aims to unveil the anti‐AD potentiality of GL through a comprehensive in silico approach involving ADMET screening, molecular docking, and molecular dynamic simulation analysis supported by in vitro analysis. ADMET analysis demonstrated higher bioavailability and lower GL toxicity. High binding affinity (> 10) of GL with key anti‐AD mediators was predicted from molecular docking study. Also, molecular dynamic simulation proves GL could fit into the 6IYC binding pocket with favorable and stable ligand‐protein interactions. In vitro DPPH analysis revealed excellent antioxidant potency of GL. MTT data showed the non‐toxic nature of GL on healthy brain cells. Outcome of the study would be helpful in futuristic studies of GL to establish it as a potent drug candidate in AD.