Metabolic Brain Disease

, Volume 34, Issue 1, pp 103–117 | Cite as

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

  • Raja Sekhar Sanna
  • Subramanyam Muthangi
  • Chandrasekhar Sagar B.K.
  • Sambe Asha DeviEmail author
Original Article


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.


Bax Bcl-2 Behavior Diabetes Grape seed proanthocyanidin Prefrontal cortex 



The studies has been supported by research grants under the Promotion of University Research and Scientific Excellence (PURSE)-Department of Science and Technology (DST) (SR/59/Z-23/2010/38 dt.27.06.2011), New Delhi and University Grants Commission-Centre for Potential Excellence in a Particular Area (UGC-CPEPA, F.No.8-2/2008(NA/PE) dt.21.12.2011), New Delhi.

Compliance with ethical standards

Conflict of interest

All authors state there is no conflict of interest.

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Raja Sekhar Sanna
    • 1
  • Subramanyam Muthangi
    • 2
  • Chandrasekhar Sagar B.K.
    • 3
  • Sambe Asha Devi
    • 1
    Email author
  1. 1.Laboratory of Gerontology, Department of ZoologyBangalore UniversityBengaluruIndia
  2. 2.Department of Life SciencesBangalore UniversityBengaluruIndia
  3. 3.Department of NeuropathologyNational Institute of Mental Health and NeurosciencesBengaluruIndia

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