Polydatin inhibits hippocampal neurodegeneration in diabetic rats via modulation of oxidative stress and NF-kB/COX-2/IL-6 inflammatory pathway.

Authors

Ahmed I Yousef, Sanaa M Abd El-Twab, Sally M Khadrawy, Adel Abdel-Moneim, Rehab G Khalil

Published in

Metabolic brain disease. Volume 41. Issue 1. Jul 09, 2026. Epub Jul 09, 2026.

Abstract

Impaired insulin function and persistent hyperglycemia damage the brain of diabetics and raise the risk of Alzheimer's disease (AD). Although polydatin (PLD) possesses promising biological effects, no major study has yet explored its anti-neurodegenerative efficacy in the hippocampus. This study therefore aims to investigate the probable protective effects of PLD against hippocampal neurodegeneration in diabetic rats, as well as explore its in-silico inhibitory activity against two key enzymes implicated in the progression of AD. Experimental diabetes was induced in male albino rats then PLD was administered orally to the diabetic rats (50 mg/kg b.wt.) daily for four weeks. In silico molecular docking was used to predict the interactions of PLD against BACE1 and AChE. PLD treatment significantly improved diabetic parameters, lowering blood glucose and raising serum insulin. Excitingly, PLD markedly alleviated oxidative stress by reducing lipid peroxidation and nitric oxide levels while enhancing antioxidant defenses (elevated GPx activity and GSH content) in the hippocampus of diabetic rats. PLD also suppressed neuroinflammation by down-regulating NF-κB, COX-2, and IL-6 mRNA expression. Furthermore, PLD significantly elevated the protein level of IDE while lowered Aβ_1-42 level. In silico, PLD revealed potent binding affinity for BACE1 (-8.6 Kcal/mol) and AChE (-10.5 Kcal/mol), interacting with key residues, indicating its inhibition potential. Overall, PLD effectively reduced neurodegeneration in the hippocampus of diabetic rats via inhibiting oxidative stress, inflammation, and Aβ_1-42 accumulation. PLD may act as a promising multi-target anti-neurodegenerative candidate, capable of simultaneously modulating multiple pathways and more experimental validation are needed in the future.

PMID:
42423809
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

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