Neuroprotective Potential of p-MCA in Drosophila
DOI:
https://doi.org/10.48048/tis.2026.13267Keywords:
p-MCA, Alzheimer’s disease, Neuroprotection, D. melanogaster, Oxidative stress, Drug discovery, Neurodegenerative disordersAbstract
p-methoxycinnamic acid (p-MCA), a bioactive compound from Kaempferia galanga, was evaluated for its neuroprotective effects in an Alzheimer’s disease (AD)-like model of Drosophila melanogaster, supported by in silico docking and molecular dynamics simulations. Toxicity screening identified 10 mM AlCl3 (aluminium chloride) as an effective concentration to induce neurodegenerative phenotypes without excessive mortality. p-MCA (0.01-0.1 mM) significantly improved survival, locomotor performance, and phototactic responses in AlCl3-exposed flies. Gene expression analysis showed upregulation of antioxidant (sod1, hsp22) and anti-aging (srl) genes, along with modulation of the apoptosis-related gene grim, indicating regulation of oxidative stress and cellular homeostasis. Computational analysis demonstrated stable binding of p-MCA to acetylcholinesterase (ΔG = ‒7.2 kcal/mol), comparable to 10-40. Collectively, these findings indicate that p-MCA mitigates AlCl3-induced neurotoxicity through multi-target mechanisms and supports its further evaluation in neurodegenerative disease models.
HIGHLIGHTS
- Demonstrates neuroprotective effects in a Drosophila Alzheimer’s model.
- Improves lifespan, locomotor activity, and cognitive performance under AlCl₃ exposure.
- Modulates expression of sod1, srl, grim, and hsp22
- Shows stable binding to AChE comparable to 10-40 in docking analysis.
- Suggests multitarget mechanisms through integrated in vivo and in silico
GRAPHICAL ABSTRACT
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