Protective effects of the natural polyphenol garcinol from Garcinia indica mitigates aluminium chloride-induced Alzheimer's-like neurodegeneration in Drosophila melanogaster.

UNLABELLED: Alzheimer's disease (AD) is a devastating neurodegenerative condition that affects millions of people affected in worldwide. Natural resources such as medicinal plants have been utilized for the treatment of various memory disorders like amnesia, dementia, Alzheimer's, and Parkinson's for a long time. This study aimed to investigate plants with therapeutic bioactivities for a range of scientific investigations focused on the neuroprotective effects of garcinol from Garcinia indica against the Aluminium chloride (AlCl3)-induced AD in the Drosophila melanogaster model. Polar and non-polar solvents were active on the G. indica fruit rind and subjected to phytochemical investigation. Garcinol was extracted from the EtOH extract of G. indica fruit rind using TLC, column chromatography, GC-MS, UV-visible, and FT-IR. In vitro free radical scavenging effect of the EtOH extract of G. indica fruit rind was studied to determine its antioxidant properties. The effect of garcinol on the interaction and predicted binding interaction of the AD-associated enzymes Amyloid-β, Acetylcholinesterase (AChE), and β-secretase was studied by the in-silico analysis. AD condition was initiated in D. melanogaster by challenging them with AlCl3, and they were pre-treated with garcinol, which is isolated from the EtOH extract of G. indica fruit rind. The effect of garcinol on the AChE activity, oxidative stress markers, and pro-inflammatory cytokines was studied using the respective assay kits. The apoptotic proteins were studied using the RT-PCR analysis. The findings of the phytochemical analysis. In silico garcinol effectively interacts with and inhibits the intermolecular Amyloid-β, AChE, and β-secretase enzymes. AD, garcinol treatment successfully moderated the amendments in behavioural and cognitive impairments, regulated the oxidative stress markers, decreased AChE activity, and reduced the pro-inflammatory cytokine levels. The RT-PCR method proved that garcinol regulated the pro- and anti-apoptotic protein expressions in the AD-induced D. melanogaster. The findings suggested that garcinol from EEGIFR acts against AlCl3-induced AD in D. melanogaster because of its anti-inflammatory, antioxidant, and apoptosis-modulating capabilities, and it may develop as a capable therapeutic agent in treating AD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-026-04763-6.