Grape seed proanthocyanidin extract and insulin prevents cognitive decline in type 1 diabetic rat by impacting Bcl-2 and Bax in the prefrontal cortex

Metab Brain Dis. 2019 Feb;34(1):103-117. doi: 10.1007/s11011-018-0320-5. Epub 2018 Oct 3.


It is frequently accepted that grape seed proanthocyanidins (GSPs) are efficient antioxidants and beneficial in improving cognitive functions. However, diabetes (T1DM)-associated declines in learning and memory and the possibilities of GSPs in overcoming this loss needs to be examined. The present study was designed to examine the correlation, if one exists, between cognitive behavior and neuronal survival in the prefrontal cortex (PFC) in streptozotocin (STZ)-induced diabetic Wistar rats as well as to further clarify whether the correlation exists. Also this study aimed to determine whether neurological structural changes in the PFC and pancreatic β-cells can be restored by grape seed proanthocyanidin extract (GSPE). At the end of 8 weeks, cognitive tests that rats given supplementation of GSPE and insulin had greater improvement in their spatial learning and memory skills and improved neuronal survival in the PFC and pancreatic β-cells compared to rats supplemented with either insulin or GSPE alone. Expression of Bax in the PFC was increased in the diabetic rats while Bcl-2 expression was decreased, and GSPE and insulin treatment reversed the expression of apoptotic proteins. Our findings on GSPE, a natural product, as a form of adjuvant therapy together with insulin treatment is suggestive of the existence of synergism between the two in attenuating diabetic complications in the pancreas and PFC.

Keywords: Bax; Bcl-2; Behavior; Diabetes; Grape seed proanthocyanidin; Prefrontal cortex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood Glucose
  • Cognitive Dysfunction / etiology
  • Cognitive Dysfunction / metabolism
  • Cognitive Dysfunction / prevention & control*
  • Diabetes Mellitus, Experimental / complications
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / metabolism
  • Grape Seed Extract / pharmacology
  • Grape Seed Extract / therapeutic use*
  • Insulin / pharmacology
  • Insulin / therapeutic use*
  • Male
  • Neurons / drug effects
  • Neurons / metabolism
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Proanthocyanidins / pharmacology
  • Proanthocyanidins / therapeutic use*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Rats
  • Rats, Wistar
  • Spatial Learning / drug effects
  • Spatial Memory / drug effects
  • bcl-2-Associated X Protein / metabolism*


  • Blood Glucose
  • Grape Seed Extract
  • Grape Seed Proanthocyanidins
  • Insulin
  • Proanthocyanidins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein