PMID- 26607467
OWN - NLM
STAT- MEDLINE
DCOM- 20160921
LR  - 20220321
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 769
DP  - 2015 Dec 15
TI  - Favorable effects of vildagliptin on metabolic and cognitive dysfunctions in 
      streptozotocin-induced diabetic rats.
PG  - 297-305
LID - S0014-2999(15)30373-3 [pii]
LID - 10.1016/j.ejphar.2015.11.033 [doi]
AB  - Progression of diabetes mellitus is accompanied by metabolic disorders together 
      with psychological deficits including cognitive dysfunctions. Herein, we used a 
      murine streptozotocin (STZ)-induced diabetes to investigate the beneficial 
      effects of vildagliptin not only on metabolic abnormalities, but also on 
      diabetes-induced cognitive decline. Sixty rats were divided randomly and equally 
      into 2 groups; one remains normal and the other serves as STZ- induced diabetic. 
      Both groups were further divided equally into 2 groups; one received vehicle and 
      the other received oral vildagliptin for 8 weeks. Cognitive behavior was assessed 
      using novel object recognition test. Blood samples were collected to measure 
      metabolic parameters and dipeptidyl peptidase (DPP)-IV activity. Brains were 
      removed and investigated for the levels of inflammatory and oxidative stress 
      markers malondialdehyde (MDA), superoxide dismutase (SOD) and tumor necrosis 
      factor-alpha (TNF-alpha), in addition to brain-derived neurotrophic factor (BDNF) and 
      relative expression of nuclear factor kappa B (NF-kappaB)/p65. Treatment of 
      STZ-induced diabetic rats with vildagliptin increased their body weight and 
      corrected diabetes-induced memory and learning impairment. Moreover, vildagliptin 
      significantly decreased serum levels of glucose and lipids (except high density 
      lipoprotein) together with brain MDA, TNF-alpha, serum DPP-IV activities and 
      NF-kappaB/p65 gene expression. On the other hand, vildagliptin significantly 
      increased brain BDNF, SOD as well as serum insulin. Results suggested that 
      vildagliptin has a protective role in counteracting both metabolic abnormalities 
      and memory deficits in diabetic rats, possibly via its anti-hyperglycemic, 
      anti-inflammatory, antioxidant effects, together with reduction of brain 
      NF-kappaB/p65 over expression.
CI  - Copyright (c) 2015 Elsevier B.V. All rights reserved.
FAU - El Batsh, Maha M
AU  - El Batsh MM
AD  - Department of Clinical Pharmacology, Faculty of Medicine, Menoufia University, 
      Egypt.
FAU - El Batch, Manal M
AU  - El Batch MM
AD  - Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Egypt.
FAU - Shafik, Noha M
AU  - Shafik NM
AD  - Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Egypt. 
      Electronic address: nohashafik2008@yahoo.com.
FAU - Younos, Ibrahim H
AU  - Younos IH
AD  - Department of Pharmacology and Clinical Pharmacy, College of Medicine and Health 
      Sciences, Sultan Qaboos University, Oman.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20151121
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nitriles)
RN  - 0 (Pyrrolidines)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - I6B4B2U96P (Vildagliptin)
RN  - PJY633525U (Adamantane)
SB  - IM
MH  - Adamantane/*analogs & derivatives/pharmacology
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Body Weight/drug effects
MH  - Brain/drug effects/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cognition/*drug effects
MH  - Diabetes Mellitus, Experimental/*metabolism/physiopathology
MH  - Male
MH  - Neuroprotective Agents/*pharmacology
MH  - Nitriles/*pharmacology
MH  - Oxidative Stress/drug effects
MH  - Pyrrolidines/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transcription Factor RelA/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vildagliptin
OTO - NOTNLM
OT  - Cognition
OT  - Diabetes mellitus
OT  - Dipeptidyl peptidase-IV
OT  - Streptozotocin
OT  - Streptozotocin (PubChem CID: 2733335)
OT  - Vildagliptin
OT  - Vildagliptin (PubChem CID: 11077541)
EDAT- 2015/11/27 06:00
MHDA- 2016/09/23 06:00
CRDT- 2015/11/27 06:00
PHST- 2015/08/15 00:00 [received]
PHST- 2015/11/16 00:00 [revised]
PHST- 2015/11/18 00:00 [accepted]
PHST- 2015/11/27 06:00 [entrez]
PHST- 2015/11/27 06:00 [pubmed]
PHST- 2016/09/23 06:00 [medline]
AID - S0014-2999(15)30373-3 [pii]
AID - 10.1016/j.ejphar.2015.11.033 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2015 Dec 15;769:297-305. doi: 10.1016/j.ejphar.2015.11.033. Epub 
      2015 Nov 21.