GSPE pre-treatment protects against long-term cafeteria diet-induced mitochondrial and inflammatory affectations in the hippocampus of rats

Nutr Neurosci. 2022 Dec;25(12):2627-2637. doi: 10.1080/1028415X.2021.1995118. Epub 2021 Nov 18.


Deregulations like the loss of sensitivity to insulin (insulin resistance) and chronic inflammation are alterations very commonly found in sporadic forms of neurodegenerative pathologies. Thus, finding strategies to protect against them, may lead to a reduction in the incidence and/or affectation of these pathologies. The grape seed-derived proanthocyanidins extract (GSPE) is a mixture of compounds highly enriched in polyphenols and flavonoids that have shown to have a wide range of therapeutic benefits due to their antioxidant and anti-inflammatory properties.

Objectives: This study aimed to assess the protective effects of a short pre-treatment of GSPE in the hippocampus against a prolonged feeding with cafeteria diet.

Methods: GSPE was administered for 10 days followed by 12 weeks of cafeteria diet. We analyzed transcriptional activity of genes and protein expression of key mediators of neurodegeneration in brain samples.

Results: Results indicated that GSPE was able to protect against cellular damage through the activation of AKT, as well as promote the maintenance of mitochondrial function by conserving the OXPHOS complexes and upregulating the antioxidant SOD.

Discussion: We observed that GSPE decreased inflammatory activation as observed through the downregulation of JNK, IL6 and TNFα, just like the reduction in reactive profile of astrocytes. Overall, the data presented here offers an interesting and hopeful initial step for future long-term studies on the beneficial effects of a supplementation of common diets with polyphenol and flavonoid substances for the amelioration of typical early hallmarks of neurodegeneration.

Keywords: GSPE; brain; cafeteria; diet; hippocampus; inflammation; metabolism; stress.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Diet
  • Hippocampus
  • Mitochondria
  • Polyphenols / pharmacology
  • Proanthocyanidins* / pharmacology
  • Rats
  • Rats, Wistar


  • Proanthocyanidins
  • Antioxidants
  • Polyphenols