Neuroprotective potential of Prunetin in streptozotocin-induced cognitive dysfunction: insights from computational and experimental studies.

Authors

Sunil Shukla, Chanchal Tiwari, Sunil Sharma, Neeru Vasudeva, Ramchander Khatri, Mohammad Ovais Dar, Tanuj Hooda, Amit Lather

Published in

Inflammopharmacology. Sep 25, 2026. Epub Sep 25, 2026.

Abstract

Type 2 diabetes mellitus (T2DM) accounts for over 85% of global diabetes cases and is strongly associated with cognitive decline resulting from chronic hyperglycemia-induced neuronal and oxidative damage. Prunetin, a natural isoflavone known for potent antioxidant and antidiabetic activity, was investigated for its potential to attenuate diabetes-associated cognitive deficits.
In silico analysis included molecular docking, MM-GBSA binding free energy, and molecular dynamics simulations (100 ns) to explore interactions between Prunetin and human acetylcholinesterase (AChE; PDB ID: 7D9O). In vivo studies were conducted in streptozotocin (STZ)-induced diabetic rats, with cognition assessed using the Morris water maze. Brain tissues were examined for Aβ(1-42), lipid peroxidation, reduced glutathione (GSH), and AChE activity to determine oxidative status and cholinergic function.
Prunetin (0.5 mg/kg/day) administered for 14 (acute) or 28 days (chronic) reduced blood glucose levels, Aβ(1-42) accumulation, and lipid peroxidation while increasing GSH levels and inhibiting AChE activity in a duration-dependent manner. These effects corresponded with significant improvements in Morris water maze performance, with 28-day treatment demonstrating greater efficacy than the 14-day regimen for most parameters. Computational modeling confirmed stable Prunetin-AChE complex formation mediated by hydrogen bonding, hydrophobic interactions, and π-π stacking interactions.
Prunetin demonstrates notable antioxidant and AChE-inhibitory properties, attenuating STZ-induced cognitive dysfunction in an experimental rat model. These findings collectively support Prunetin as a promising multitarget candidate warranting further investigation for diabetes-associated neurodegeneration.

PMID:
42789218
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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